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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Antibody Fragments as Potential Biopharmaceuticals for Cancer Therapy: Success and Limitations

Author(s): Roman V. Kholodenko*, Daniel V. Kalinovsky, Igor I. Doronin, Eugene D. Ponomarev and Irina V. Kholodenko

Volume 26, Issue 3, 2019

Page: [396 - 426] Pages: 31

DOI: 10.2174/0929867324666170817152554

Price: $65

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Abstract

Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system. Fragments of antibodies retain antigen specificity and part of functional properties of conventional mAbs and at the same time have much better penetration into the tumors and a greatly reduced level of adverse effects. Recent advantages in antibody engineering allowed to produce different types of antibody fragments with improved structure and properties for efficient elimination of tumor cells. These molecules opened up new perspectives for anticancer therapy. Here, we will overview the structural features of the various types of antibody fragments and their applications for anticancer therapy as separate molecules and as part of complex conjugates or structures. Mechanisms of antitumor action of antibody fragments as well as their advantages and disadvantages for clinical application will be discussed in this review.

Keywords: Antitumor therapy, monoclonal antibodies, fragments of monoclonal antibodies, tumor cell death, ligand-targeted drugs, targeted nanoparticles, immunocytokines, bispecific antibodies.

[1]
Deyev, S.M.; Lebedenko, E.N. Modern technologies for creating synthetic antibodies for clinical application. Acta Naturae, 2009, 1(1), 32-50.
[2]
Pluen, A.; Boucher, Y.; Ramanujan, S.; McKee, T.D.; Gohongi, T.; di Tomaso, E.; Brown, E.B.; Izumi, Y.; Campbell, R.B.; Berk, D.A.; Jain, R.K. Role of tumor-host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc. Natl. Acad. Sci. USA, 2001, 98(8), 4628-4633.
[3]
Khawli, L.A.; Biela, B.; Hu, P.; Epstein, A.L. Comparison of recombinant derivatives of chimeric TNT-3 antibody for the radioimaging of solid tumors. Hybrid. Hybridomics, 2003, 22(1), 1-9.
[4]
Tahtis, K.; Lee, F.T.; Smyth, F.E.; Power, B.E.; Renner, C.; Brechbiel, M.W.; Old, L.J.; Hudson, P.J.; Scott, A.M. Biodistribution properties of (111)indium-labeled C-functionalized trans-cyclohexyl diethylenetriaminepentaacetic acid humanized 3S193 diabody and F(ab’)(2) constructs in a breast carcinoma xenograft model. Clin. Cancer Res., 2001, 7(4), 1061-1072.
[5]
Thurber, G.M.; Wittrup, K.D. Quantitative spatiotemporal analysis of antibody fragment diffusion and endocytic consumption in tumor spheroids. Cancer Res., 2008, 68(9), 3334-3341.
[6]
Hudson, P.J. Recombinant antibody fragments. Curr. Opin. Biotechnol., 1998, 9(4), 395-402.
[7]
Fisher, A.C.; Haitjema, C.H.; Guarino, C.; Çelik, E.; Endicott, C.E.; Reading, C.A.; Merritt, J.H.; Ptak, A.C.; Zhang, S.; DeLisa, M.P. Production of secretory and extracellular N-linked glycoproteins in Escherichia coli. Appl. Environ. Microbiol., 2011, 77(3), 871-881.
[8]
Usta, C.; Turgut, N.T.; Bedel, A. How abciximab might be clinically useful. Int. J. Cardiol., 2016, 222, 1074-1078.
[9]
Moja, L.; Lucenteforte, E.; Kwag, K.H.; Bertele, V.; Cam-pomori, A.; Chakravarthy, U.; D’Amico, R.; Dickersin, K.; Kodjikian, L.; Lindsley, K.; Loke, Y. Maguire., M; Martin, D.F.; Mugelli, A.; Mühlbauer, B.; Püntmann, I.; Reeves, B.; Rogers, C.; Schmucker, C.; Subramanian, M.L.; Virgili, G. Systemic safety of bevacizumab versus ranibizumab for neo-vascular age-related macular degeneration. Cochrane Database Syst. Rev., 2014, 9, CD011230.
[10]
Schmucker, C.; Ehlken, C.; Agostini, H.T.; Antes, G.; Ruecker, G.; Lelgemann, M.; Loke, Y.K. A safety review and meta-analyses of bevacizumab and ranibizumab: Off-label versus goldstandard. PLoS One, 2012, 7(8), e42701.
[11]
Goel, N.; Stephens, S. Certolizumab pegol. MAbs, 2010, 2(2), 137-147.
[12]
Ruiz Garcia, V.; Jobanputra, P.; Burls, A.; Cabello, J.B.; Vela Casasempere, P.; Bort-Marti, S.; Kynaston-Pearson, F.J. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults. Cochrane Database Syst. Rev., 2014, 9(9), CD007649.
[13]
Sandborn, W.J.; Feagan, B.G.; Stoinov, S.; Honiball, P.J.; Rutgeerts, P.; Mason, D.; Bloomfield, R.; Schreiber, S. Certolizumab pegol for the treatment of Crohn’s disease. N. Engl. J. Med., 2007, 357(3), 228-238.
[14]
Mease, P.J.; Fleischmann, R.; Deodhar, A.A.; Wollenhaupt, J.; Khraishi, M.; Kielar, D.; Woltering, F.; Stach, C.; Hoep-ken, B.; Arledge, T.; van der Heijde, D. Effect of certoli-zumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind ran-domized placebo-controlled study (RAPID-PsA). Ann. Rheum. Dis., 2013, 1-8.
[15]
Sieper, J.; Tubergen, A.; Coteur, G.; Woltering, F.; Landewe, R. PMS50 – rapid improvements in patient-reported out-comes with certolizumab pegol in patients with axial spondy-loarthritis, including ankylosing spondylitis and non-radiographic axial spondyloarthritis: 24-week results of a Phase 3 double blind randomized placebo-controlled study. Value Health, 2013, 16(3), A227.
[16]
Goswami, S.; Wang, W.; Arakawa, T.; Ohtake, S. Develop-ments and challenges for mAb-based ttherapeutics. Antibodies (Basel), 2013, 2, 452-500.
[17]
Herrington-Symes, A.P.; Farys, M.; Khalili, H.; Brocchini, S. Antibody fragments: prolonging circulation half-life special issue-antibody research. Adv. Biosci. Biotechnol., 2013, 4, 689-698.
[18]
Nelson, A.L. Antibody fragments: Hope and hype. MAbs, 2010, 2(1), 77-83.
[19]
Reichert, J.M. Antibodies to watch in 2017. MAbs, 2016, 14, 1-15.
[20]
Lonberg, N. Human antibodies from transgenic animals. Nat. Biotechnol., 2005, 23(9), 1117-1125.
[21]
Nelson, A.L.; Reichert, J.M. Development trends for therapeutic antibody fragments. Nat. Biotechnol., 2009, 27(4), 331-337.
[22]
Gramlick, G.; Fossati, G.; Nesbitt, A.; Henry, A.J. Neutrali-zation of soluble and membrane tumour necrosis factor α by infliximab, adalimumab or certolizumab pegol using p55 or p75 TNFα receptor bioassay. Gastroenterology, 2006, 130(4), 697.
[23]
Pollack, C.V., Jr; Reilly, P.A.; Eikelboom, J.; Glund, S.; Verhamme, P.; Bernstein, R.A.; Dubiel, R.; Huisman, M.V.; Hylek, E.M.; Kamphuisen, P.W.; Kreuzer, J.; Levy, J.H.; Sellke, F.W.; Stangier, J.; Steiner, T.; Wang, B.; Kam, C-W.; Weitz, J.I. Idarucizumab for dabigatran reversal. N. Engl. J. Med., 2015, 373(6), 511-520.
[24]
Ip, D.; Syed, H.; Cohen, M. Digoxin specific antibody fragments (Digibind) in digoxin toxicity. BMJ, 2009, 339, b2884.
[25]
Chames, P.; Van Regenmortel, M.; Weiss, E.; Baty, D. Therapeutic antibodies: Successes, limitations and hopes for the future. Br. J. Pharmacol., 2009, 157(2), 220-233.
[26]
Gaudreault, J.; Fei, D.; Rusit, J.; Suboc, P.; Shiu, V. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest. Ophthalmol. Vis. Sci., 2005, 46(2), 726-733.
[27]
Shock, A.; Burkly, L.; Wakefield, I.; Peters, C.; Garber, E.; Ferrant, J.; Taylor, F.R.; Su, L.; Hsu, Y.M.; Hutto, D.; Amirkhosravi, A.; Meyer, T.; Francis, J.; Malcolm, S.; Robinson, M.; Brown, D.; Shaw, S.; Foulkes, R.; Lawson, A.; Harari, O.; Bourne, T.; Maloney, A.; Weir, N. CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. Arthritis Res. Ther., 2015, 17, 234.
[28]
Hawkins, R.E.; Gore, M.; Shparyk, Y.; Bondar, V.; Gladkov, O.; Ganev, T.; Harza, M.; Polenkov, S.; Bondarenko, I.; Karlov, P.; Karyakin, O.; Khasanov, R.; Hedlund, G.; Forsberg, G.; Nordle, Ö.; Eisen, T. A randomized Phase II/III study of naptumomab estafenatox + IFNα versus IFNα in renal cell carcinoma: final analysis with baseline biomarker subgroup and trend analysis. Clin. Cancer Res., 2016, 22(13), 3172-3181.
[29]
Mamot, C.; Drummond, D.C.; Noble, C.O.; Kallab, V.; Guo, Z.; Hong, K.; Kirpotin, D.B.; Park, J.W. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res., 2005, 65(24), 11631-11638.
[30]
Mamot, C.; Ritschard, R.; Vogel, B.; Dieterle, T.; Bubendorf, L.; Hilker, C.; Deuster, S.; Herrmann, R.; Rochlitz, C. Targeting radioimmunother-apy of hepatocellular carcinoma with iodine (131I) metuxi-mab injection: Clinical Phase I/II trials. Int. J. Radiat. Oncol. Biol. Phys., 2006, 65(2), 435-444.
[31]
Chen, Z.N.; Mi, L.; Xu, J.; Song, F.; Zhang, Q.; Zhang, Z.; Xing, J.L.; Bian, H.J.; Jiang, J.L.; Wang, X.H.; Shang, P.; Qian, A.R.; Zhang, S.H.; Li, L.; Li, Y.; Feng, Q.; Yu, X.L.; Feng, Y.; Yang, X.M.; Tian, R.; Wu, Z.B.; Leng, N.; Mo, T.S.; Kuang, A.R.; Tan, T.Z.; Li, Y.C.; Liang, D.R.; Lu, W.S.; Miao, J.; Xu, G.H.; Zhang, Z.H.; Nan, K.J.; Han, J.; Liu, Q.G.; Zhang, H.X.; Zhu, P. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical phase I/II trials. Int. J. Radiat. Oncol. Biol. Phys., 2006, 65(2), 435-444.
[32]
Zhang, M-Y.; Lu, J-J.; Wang, L.; Gao, Z-C.; Hu, H.; Lam Ung, C.O.; Wang, Y-T. Development of monoclonal antibodies in China: Overview and prospects , 2015. BioMed Res. Int2015 Article ID 168935, 10 pages
[33]
Boyer, L.V.; Chase, P.B.; Degan, J.A.; Figge, G.; Buelna-Romero, A.; Luchetti, C.; Alagón, A. Subacute coagulopathy in a randomized, comparative trial of Fab and F(ab’)2 antivenoms. Toxicon, 2013, 74, 101-108.
[34]
Bush, S.P.; Ruha, A-M.; Seifert, S.A.; Morgan, D.L.; Lewis, B.J.; Arnold, T.C.; Clark, R.F.; Meggs, W.J.; Toschlog, E.A.; Borron, S.W.; Figge, G.R.; Sollee, D.R.; Shirazi, F.M.; Wolk, R.; de Chazal, I.; Quan, D.; García-Ubbelohde, W.; Alagón, A.; Gerkin, R.D.; Boyer, L.V. Comparison of F(ab’)2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. Clin. Toxicol. (Phila.), 2015, 53(1), 37-45.
[35]
Johnson, M. Antibody structure and fragments., 2013.https://www.labome.com/method/ Antibody-Structure-and-Fragments.html
[36]
Albrecht, H.; Burke, P.A.; Natarajan, A.; Xiong, C-Y.; Kalicinsky, M.; DeNardo, G.L.; DeNardo, S.J. Production of soluble ScFvs with C-terminal-free thiol for site-specific conjugation or stable dimeric ScFvs on demand. Bioconjug. Chem., 2004, 15(1), 16-26.
[37]
Ahmad, Z.A.; Yeap, S.K.; Ali, A.M.; Ho, W.Y.; Alitheen, N.B.; Hamid, M. scFv Antibody: Principles and clinical applicationClin. Develop. Immunol; , 2012. Vol. 2012, Article ID 980250, 15 pages.
[38]
Gupta, S.K.; Shukla, P. Microbial platform technology for recombinant antibody fragment production: A review. Crit. Rev. Microbiol., 2017, 43(1), 31-42.
[39]
Holliger, P.; Prospero, T.; Winter, G. “Diabodies”: Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA, 1993, 90(14), 6444-6448.
[40]
Iliades, P.; Kortt, A.A.; Hudson, P.J. Triabodies: Single chain Fv fragments without a linker form trivalent trimers. FEBS Lett., 1997, 409(3), 437-441.
[41]
Todorovska, A.; Roovers, R.C.; Dolezal, O.; Kortt, A.A.; Hoogenboom, H.R.; Hudson, P.J. Design and application of diabodies, triabodies and tetrabodies for cancer targeting. J. Immunol. Methods, 2001, 248(1-2), 47-66.
[42]
Turner, D.J.; Ritter, M.A.; George, A.J. Importance of the linker in expression of single-chain Fv antibody fragments: optimisation of peptide sequence using phage display technology. J. Immunol. Methods, 1997, 205(1), 43-54.
[43]
Zdanov, A.; Li, Y.; Bundle, D.R.; Deng, S-J.; MacKenzie, C.R.; Narang, S.A.; Young, N.M.; Cygler, M. Structure of a single-chain antibody variable domain (Fv) fragment complexed with a carbohydrate antigen at 1.7-A resolution. Proc. Natl. Acad. Sci. USA, 1994, 91(14), 6423-6427.
[44]
Kortt, A.A.; Lah, M.; Oddie, G.W.; Gruen, C.L.; Burns, J.E.; Pearce, L.A.; Atwell, J.L.; McCoy, A.J.; Howlett, G.J.; Metzger, D.W.; Webster, R.G.; Hudson, P.J. Single-chain Fv fragments of anti-neuraminidase antibody NC10 containing five- and ten-residue linkers form dimers and with zero-residue linker a trimer. Protein Eng., 1997, 10(4), 423-433.
[45]
Atwell, J.; Breheney, K.A.; Lawrence, L.J.; McCoy, A.J.; Kortt, A.A.; Hudson, P.J. scFv Multimers: Length of the linker between V and V domains dictates precisely the transition between diabodies and triabodies. Protein Eng., 1999, 12(7), 597-604.
[46]
Dolezal, O.; Pearce, L.A.; Lawrence, L.J.; McCoy, A.J.; Hudson, P.J.; Kortt, A.A. ScFv multimers of the anti-neuraminidase antibody NC10: shortening of the linker in single-chain Fv fragment assembled in V(L) to V(H) orientation drives the formation of dimers, trimers, tetramers and higher molecular mass multimers. Protein Eng., 2000, 13(8), 565-574.
[47]
Kortt, A.A.; Dolezal, O.; Power, B.E.; Hudson, P.J. Dimeric and trimeric antibodies: High avidity scFvs for cancer targeting. Biomol. Eng., 2001, 18(3), 95-108.
[48]
Le Gall, F.; Kipriyanov, S.M.; Moldenhauer, G.; Little, M. Di-, tri- and tetrameric single chain Fv antibody fragments against human CD19: effect of valency on cell binding. FEBS Lett., 1999, 453(1-2), 164-168.
[49]
Power, B.E.; Doughty, L.; Shapira, D.R.; Burns, J.E.; Bayly, A.M.; Caine, J.M.; Liu, Z.; Scott, A.M.; Hudson, P.J.; Kortt, A.A. Noncovalent scFv multimers of tumor-targeting anti-Lewis(y) hu3S193 humanized antibody. Protein Sci., 2003, 12(4), 734-747.
[50]
Willuda, J.; Kubetzko, S.; Waibel, R.; Schubiger, P.A.; Zangemeister-Wittke, U.; Plückthun, A. Tumor targeting of mono-, di-, and tetravalent anti-p185(HER-2) miniantibodies multimerized by self-associating peptides. J. Biol. Chem., 2001, 276(17), 14385-14392.
[51]
Asano, R.; Hagiwara, Y.; Koyama, N.; Masakari, Y.; Orimo, R.; Arai, K.; Ogata, H.; Furumoto, S.; Umetsu, M.; Kumagai, I. Multimerization of anti-(epidermal growth factor receptor) IgG fragments induces an antitumor effect: the case for humanized 528 scFv multimers. FEBS J., 2013, 280(19), 4816-4826.
[52]
Asano, R.; Koyama, N.; Hagiwara, Y.; Masakari, Y.; Orimo, R.; Arai, K.; Ogata, H.; Furumoto, S.; Umetsu, M.; Kumagai, I. Anti-EGFR scFv tetramer (tetrabody) with a stable monodisperse structure, strong anticancer effect, and a long in vivo half-life. FEBS Open Bio, 2016, 6(6), 594-602.
[53]
Holliger, P.; Hudson, P.J. Engineered antibody fragments and the rise of single domains. Nat. Biotechnol., 2005, 23(9), 1126-1136.
[54]
Hu, S.; Shively, L.; Raubitschek, A.; Sherman, M.; Williams, L.E.; Wong, J.Y.C.; Shively, J.E.; Wu, A.M. Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer Res., 1996, 56(13), 3055-3061.
[55]
Shahied, L.S.; Tang, Y.; Alpaugh, R.K.; Somer, R.; Greenspon, D.; Weiner, L.M. Bispecific minibodies targeting HER2/neu and CD16 exhibit improved tumor lysis when placed in a divalent tumor antigen binding format. J. Biol. Chem., 2004, 279(52), 53907-53914.
[56]
Wörn, A.; Plückthun, A. Stability engineering of antibody single-chain Fv fragments. J. Mol. Biol., 2001, 305(5), 989-1010.
[57]
Tang, Y.; Jiang, N.; Parakh, C.; Hilvert, D. Selection of linkers for a catalytic single-chain antibody using phage display technology. J. Biol. Chem., 1996, 271(26), 15682-15686.
[58]
Kim, Y.P.; Park, D.; Kim, J.J.; Chi, W.J.; Lee, S.H.; Lee, S.Y.; Kim, S.; Chung, J.M.; Jeon, J.; Lee, B.D.; Shin, J.H.; Lee, Y.I.; Cho, H.; Lee, J.M.; Kang, H.C. Effective therapeutic approach for head and neck cancer by an engineered minibody targeting the EGFR receptor. PLoS One, 2014, 9(12), e113442.
[59]
Ayala, M.; Balint, R.F.; Fernández-de-Cossío, L.; Canaán-Haden, J.W.; Larrick, J.W.; Gavilondo, J.V. Variable region sequence modulates periplasmic export of a single-chain Fv antibody fragment in Escherichia coli. Biotechniques, 1995, 18 (5), 832-, 835-838, 840-842
[60]
Watanabe, R.; Hanaoka, H.; Sato, K.; Nagaya, T.; Harada, T.; Mitsunaga, M.; Kim, I.; Paik, C.H.; Wu, A.M.; Choyke, P.L.; Kobayashi, H. Photoimmunotherapy targeting prostate-specific membrane antigen: are antibody fragments as effective as antibodies? J. Nucl. Med., 2015, 56(1), 140-144.
[61]
Chiu, G.N.; Edwards, L.A.; Kapanen, A.I.; Malinen, M.M.; Dragowska, W.H.; Warburton, C.; Chikh, G.G.; Fang, K.Y.; Tan, S.; Sy, J.; Tucker, C.; Waterhouse, D.N.; Klasa, R.; Bally, M.B. Modulation of cancer cell survival pathways using multivalent liposomal therapeutic antibody constructs. Mol. Cancer Ther., 2007, 6(3), 844-855.
[62]
Park, J.W.; Hong, K.; Carter, P.; Asgari, H.; Guo, L.Y.; Keller, G.A.; Wirth, C.; Shalaby, R.; Kotts, C.; Wood, W.I. Development of anti-p185HER2 immunoliposomes for cancer therapy. Proc. Natl. Acad. Sci. USA, 1995, 92(5), 1327-1331.
[63]
Jølck, R.I.; Feldborg, L.N.; Andersen, S.; Moghimi, S.M.; Andresen, T.L. Engineering liposomes and nanoparticles for biological targeting. Adv. Biochem. Eng. Biotechnol., 2011, 125, 251-280.
[64]
Hamers-Casterman, C.; Atarhouch, T.; Muyldermans, S.; Robinson, G.; Hamers, C.; Songa, E.B.; Bendahman, N.; Hamers, R. Naturally occurring antibodies devoid of light chains. Nature, 1993, 363(6428), 446-448.
[65]
Ungar-Waron, H.; Elias, E.; Gluckman, A.; Trainin, Z. Dromedary IgG, purification, characterization and quantita-tion in sera of dams and newborn. Isr. J. Vet. Med., 1987, 43, 198-203.
[66]
De Vos, J.; Devoogdt, N.; Lahoutte, T.; Muyldermans, S. Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications: adjusting the bullet to its target. Expert Opin. Biol. Ther., 2013, 13(8), 1149-1160.
[67]
Hassanzadeh-Ghassabeh, G.; Devoogdt, N.; De Pauw, P.; Vincke, C.; Muyldermans, S. Nanobodies and their potential applications. Nanomedicine (Lond.), 2013, 8(6), 1013-1026.
[68]
Flajnik, M.F.; Deschacht, N.; Muyldermans, S. A case of convergence: Why did a simple alternative to canonical antibodies arise in sharks and camels? PLoS Biol., 2011, 9(8), e1001120.
[69]
De Genst, E.; Saerens, D.; Muyldermans, S.; Conrath, K. Antibody repertoire development in camelids. Dev. Comp. Immunol., 2006, 30(1-2), 187-198.
[70]
Roovers, R.C.; van Dongen, G.A. van Bergen en Henegouwen, P.M. Nanobodies in therapeutic applications. Curr. Opin. Mol. Ther., 2007, 9(4), 327-335.
[71]
De Meyer, T.; Muyldermans, S.; Depicker, A. Nanobody-based products as research and diagnostic tools. Trends Biotechnol., 2014, 32(5), 263-270.
[72]
van den Berg, A.; Dowdy, S.F. Protein transduction domain delivery of therapeutic macromolecules. Curr. Opin. Biotechnol., 2011, 22(6), 888-893.
[73]
Abulrob, A.; Sprong, H. Van Bergen en Henegouwen, P.; Stanimirovic, D. The blood-brain barrier transmigrating sin-gle domain antibody: Mechanisms of transport and antigenic epitopes in human brain endothelial cells. J. Neurochem., 2005, 95(4), 1201-1214.
[74]
Lafaye, P.; Achour, I.; England, P.; Duyckaerts, C.; Rougeon, F. Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation. Mol. Immunol., 2009, 46(4), 695-704.
[75]
Revets, H.; De Baetselier, P.; Muyldermans, S. Nanobodies as novel agents for cancer therapy. Expert Opin. Biol. Ther., 2005, 5(1), 111-124.
[76]
Mujić-Delić, A.; de Wit, R.H.; Verkaar, F.; Smit, M.J. GPCR-targeting nanobodies: Attractive research tools, diagnostics, and therapeutics. Trends Pharmacol. Sci., 2014, 35(5), 247-255.
[77]
Vincke, C.; Muyldermans, S. Introduction to heavy chain antibodies and derived nanobodies. Methods Mol. Biol., 2012, 911, 15-26.
[78]
Cortez-Retamozo, V.; Backmann, N.; Senter, P.D.; Wernery, U.; De Baetselier, P.; Muyldermans, S.; Revets, H. Efficient cancer therapy with a nanobody-based conjugate. Cancer Res., 2004, 64(8), 2853-2857.
[79]
Rahbarizadeh, F.; Ahmadvand, D.; Sharifzadeh, Z. Nanobody; an old concept and new vehicle for immunotargeting. Immunol. Invest., 2011, 40(3), 299-338.
[80]
Sadeqzadeh, E.; Rahbarizadeh, F.; Ahmadvand, D.; Rasaee, M.J.; Parhamifar, L.; Moghimi, S.M. Combined MUC1-specific nanobody-tagged PEG-polyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells. J. Control. Release, 2011, 156(1), 85-91.
[81]
Vaneycken, I.; Devoogdt, N.; Van Gassen, N.; Vincke, C.; Xavier, C.; Wernery, U.; Muyldermans, S.; Lahoutte, T.; Caveliers, V. Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer. FASEB J., 2011, 25(7), 2433-2446.
[82]
Sharifzadeh, Z.; Rahbarizadeh, F.; Shokrgozar, M.A.; Ahmadvand, D.; Mahboudi, F.; Jamnani, F.R.; Moghimi, S.M. Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents. Cancer Lett., 2013, 334(2), 237-244.
[83]
Roovers, R.C.; Laeremans, T.; Huang, L.; De Taeye, S.; Verkleij, A.J.; Revets, H.; de Haard, H.J. van Bergen en Henegouwen, P.M. Efficient inhibition of EGFR signalling and of tumour growth by antagonistic anti-EGFR nanobod-ies. Cancer Immunol. Immunother., 2007, 56(3), 303-317.
[84]
Roovers, R.C.; Vosjan, M.J.; Laeremans, T.; el Khoulati, R.; de Bruin, R.C.; Ferguson, K.M.; Verkleij, A.J.; van Dongen, G.A. van Bergen en Henegouwen, P.M. A biparatopic anti-EGFR nanobody efficiently inhibits solid tumour growth. Int. J. Cancer, 2011, 129(8), 2013-2024.
[85]
Slørdahl, T.S.; Denayer, T.; Moen, S.H.; Standal, T.; Børset, M.; Ververken, C.; Rø, T.B. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment. Eur. J. Haematol., 2013, 91(5), 399-410.
[86]
Vosjan, M.J.; Vercammen, J.; Kolkman, J.A.; Stigter-van Walsum, M.; Revets, H.; van Dongen, G.A. Nanobodies targeting the hepatocyte growth factor: potential new drugs for molecular cancer therapy. Mol. Cancer Ther., 2012, 11(4), 1017-1025.
[87]
Behdani, M.; Zeinali, S.; Khanahmad, H.; Karimipour, M.; Asadzadeh, N.; Azadmanesh, K.; Khabiri, A.; Schoonooghe, S.; Habibi Anbouhi, M.; Hassanzadeh-Ghassabeh, G.; Muyldermans, S. Generation and characterization of a functional Nanobody against the vascular endothelial growth factor receptor-2; angiogenesis cell receptor. Mol. Immunol., 2012, 50(1-2), 35-41.
[88]
Kijanka, M.; Dorresteijn, B.; Oliveira, S. van Bergen en Henegouwen, P.M. Nanobody-based cancer therapy of solid tumors. Nanomedicine (Lond.), 2015, 10(1), 161-174.
[89]
Stuckey, D.W.; Hingtgen, S.D.; Karakas, N.; Rich, B.E.; Shah, K. Engineering toxin-resistant therapeutic stem cells to treat brain tumors. Stem Cells, 2015, 33(2), 589-600.
[90]
Goyvaerts, C.; De Groeve, K.; Dingemans, J.; Van Lint, S.; Robays, L.; Heirman, C.; Reiser, J.; Zhang, X.Y.; Thielemans, K.; De Baetselier, P.; Raes, G.; Breckpot, K. Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells. Gene Ther., 2012, 19(12), 1133-1140.
[91]
Hernot, S.; Unnikrishnan, S.; Du, Z.; Shevchenko, T.; Cosyns, B.; Broisat, A.; Toczek, J.; Caveliers, V.; Muyldermans, S.; Lahoutte, T.; Klibanov, A.L.; Devoogdt, N. Nanobody-coupled microbubbles as novel molecular tracer. J. Control. Release, 2012, 158(2), 346-353.
[92]
Van de Broek, B.; Devoogdt, N.; D’Hollander, A.; Gijs, H-L.; Jans, K.; Lagae, L.; Muyldermans, S.; Maes, G.; Borghs, G. Specific cell targeting with nanobody conjugated branched gold nanoparticles for photothermal therapy. ACS Nano, 2011, 5(6), 4319-4328.
[93]
Altintas, I.; Kok, R.J.; Schiffelers, R.M. Targeting epidermal growth factor receptor in tumors: from conventional monoclonal antibodies via heavy chain-only antibodies to nanobodies. Eur. J. Pharm. Sci., 2012, 45(4), 399-407.
[94]
Shishido, T.; Azumi, Y.; Nakanishi, T.; Umetsu, M.; Tanaka, T.; Ogino, C.; Fukuda, H.; Kondo, A. Biotinylated bionanocapsules for displaying diverse ligands toward cell-specific delivery. J. Biochem., 2009, 146(6), 867-874.
[95]
Talelli, M.; Rijcken, C.J.; Oliveira, S.; van der Meel, R.; van Bergen En Henegouwen, P.M.; Lammers, T.; van Nostrum, C.F.; Storm, G.; Hennink, W.E. Nanobody-shell functionalized thermosensitive core-crosslinked polymeric micelles for active drug targeting. J. Control. Release, 2011, 151(2), 183-192.
[96]
Moores, S.L.; Chiu, M.L.; Bushey, B.S.; Chevalier, K.; Luistro, L.; Dorn, K.; Brezski, R.J.; Haytko, P.; Kelly, T.; Wu, S.J.; Martin, P.L.; Neijssen, J.; Parren, P.W.; Schuurman, J.; Attar, R.M.; Laquerre, S.; Lorenzi, M.V.; Anderson, G.M. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res., 2016, 76(13), 3942-3953.
[97]
Nisonoff, A.; Mandy, W.J. Quantitative estimation of the hybridization of rabbit antibodies. Nature, 1962, 194, 355-359.
[98]
James, N.D.; Atherton, P.J.; Jones, J.; Howie, A.J.; Tchekmedyian, S.; Curnow, R.T. A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer. Br. J. Cancer, 2001, 85(2), 152-156.
[99]
Lindhofer, H.; Mocikat, R.; Steipe, B.; Thierfelder, S. Preferential species-restricted heavy/light chain pairing in rat/mouse quadromas. Implications for a single-step purification of bispecific antibodies. J. Immunol., 1995, 155(1), 219-225.
[100]
Byrne, H.; Conroy, P.J.; Whisstock, J.C.; O’Kennedy, R.J. A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications. Trends Biotechnol., 2013, 31(11), 621-632.
[101]
Linke, R.; Klein, A.; Seimetz, D. Catumaxomab: clinical development and future directions. MAbs, 2010, 2(2), 129-136.
[102]
Heiss, M.M.; Murawa, P.; Koralewski, P.; Kutarska, E.; Kolesnik, O.O.; Ivanchenko, V.V.; Dudnichenko, A.S.; Aleknaviciene, B.; Razbadauskas, A.; Gore, M.; Ganea-Motan, E.; Ciuleanu, T.; Wimberger, P.; Schmittel, A.; Schmalfeldt, B.; Burges, A.; Bokemeyer, C.; Lindhofer, H.; Lahr, A.; Parsons, S.L. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial. Int. J. Cancer, 2010, 127(9), 2209-2221.
[103]
Spiess, C.; Merchant, M.; Huang, A.; Zheng, Z.; Yang, N.Y.; Peng, J.; Ellerman, D.; Shatz, W.; Reilly, D.; Yansura, D.G.; Scheer, J.M. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat. Biotechnol., 2013, 31(8), 753-758.
[104]
Schaefer, W.; Regula, J.T.; Bähner, M.; Schanzer, J.; Croas-dale, R.; Dürr, H.; Gassner, C.; Georges, G.; Kettenberger, H. Imhof-Jung, S.; Schwaiger, M.; Stubenrauch, K.G.; Sustmann, C.; Thomas, M.; Scheuer, W.; Klein, C. Immuno-globulin domain crossover as a generic approach for the pro-duction of bispecific IgG antibodies. Proc. Natl. Acad. Sci. USA, 2011, 108(27), 11187-11192.
[105]
Rossi, E.A.; Goldenberg, D.M.; Cardillo, T.M.; McBride, W.J.; Sharkey, R.M.; Chang, C.H. Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc. Natl. Acad. Sci. USA, 2006, 103(18), 6841-6846.
[106]
Schuurman, J.; Graus, Y.F.; Labrijn, A.F.; Ruuls, S.; Parren, P.W. Opening the door to innovation. MAbs, 2014, 6(4), 812-819.
[107]
Wu, C.; Ying, H.; Grinnell, C.; Bryant, S.; Miller, R.; Clabbers, A.; Bose, S.; McCarthy, D.; Zhu, R.R.; Santora, L.; Davis-Taber, R.; Kunes, Y.; Fung, E.; Schwartz, A.; Sakorafas, P.; Gu, J.; Tarcsa, E.; Murtaza, A.; Ghayur, T. Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat. Biotechnol., 2007, 25(11), 1290-1297.
[108]
Spiess, C.; Zhai, Q.; Carter, P.J. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol. Immunol., 2015, 67(2 Pt A), 95-106.
[109]
Albrecht, H.; Denardo, G.L.; Denardo, S.J. Monospecific bivalent scFv-SH: effects of linker length and location of an engineered cysteine on production, antigen binding activity and free SH accessibility. J. Immunol. Methods, 2006, 310(1-2), 100-116.
[110]
Baeuerle, P.A.; Reinhardt, C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res., 2009, 69(12), 4941-4944.
[111]
Müller, D.; Kontermann, R.E. Bispecific antibodies for cancer immunotherapy: Current perspectives. BioDrugs, 2010, 24(2), 89-98.
[112]
Baeuerle, P.A.; Kufer, P.; Bargou, R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr. Opin. Mol. Ther., 2009, 11(1), 22-30.
[113]
Dreier, T.; Lorenczewski, G.; Brandl, C.; Hoffmann, P.; Syring, U.; Hanakam, F.; Kufer, P.; Riethmuller, G.; Bargou, R.; Baeuerle, P.A. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int. J. Cancer, 2002, 100(6), 690-697.
[114]
Kontermann, R.E.; Brinkmann, U. Bispecific antibodies. Drug Discov. Today, 2015, 20(7), 838-847.
[115]
Moore, P.A.; Zhang, W.; Rainey, G.J.; Burke, S.; Li, H.; Huang, L.; Gorlatov, S.; Veri, M.C.; Aggarwal, S.; Yang, Y.; Shah, K.; Jin, L.; Zhang, S.; He, L.; Zhang, T.; Ciccarone, V.; Koenig, S.; Bonvini, E.; Johnson, S. Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma. Blood, 2011, 117(17), 4542-4551.
[116]
Chen, S.; Li, J.; Li, Q.; Wang, Z. Bispecific antibodies in cancer immunotherapy. Hum. Vaccin. Immunother., 2016, 12(10), 2491-2500.
[117]
Fan, D.; Li, Z.; Zhang, X.; Yang, Y.; Yuan, X.; Zhang, X.; Yang, M.; Zhang, Y.; Xiong, D. AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells. J. Hematol. Oncol., 2015, 8(18), 18.
[118]
Fan, G.; Wang, Z.; Hao, M.; Li, J. Bispecific antibodies and their applications. J. Hematol. Oncol., 2015, 8, 130.
[119]
Weiner, G.J. Building better monoclonal antibody-based therapeutics. Nat. Rev. Cancer, 2015, 15(6), 361-370.
[120]
Neri, D.; Sondel, P.M. Immunocytokines for cancer treatment: past, present and future. Curr. Opin. Immunol., 2016, 40, 96-102.
[121]
Chelius, D.; Ruf, P.; Gruber, P.; Plöscher, M.; Liedtke, R.; Gansberger, E.; Hess, J.; Wasiliu, M.; Lindhofer, H. Structural and functional characterization of the trifunctional antibody catumaxomab. MAbs, 2010, 2(3), 309-319.
[122]
Zeidler, R.; Mysliwietz, J.; Csánady, M.; Walz, A.; Ziegler, I.; Schmitt, B.; Wollenberg, B.; Lindhofer, H. The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells. Br. J. Cancer, 2000, 83(2), 261-266.
[123]
Berek, J.S.; Edwards, R.P.; Parker, L.P.; DeMars, L.R.; Herzog, T.J.; Lentz, S.S.; Morris, R.T.; Akerley, W.L.; Holloway, R.W.; Method, M.W.; Plaxe, S.C.; Walker, J.L.; Friccius-Quecke, H.; Krasner, C.N. Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study. Int. J. Gynecol. Cancer, 2014, 24(9), 1583-1589.
[124]
Seimetz, D.; Lindhofer, H.; Bokemeyer, C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat. Rev., 2010, 36(6), 458-467.
[125]
Jäger, M.; Schoberth, A.; Ruf, P.; Hess, J.; Lindhofer, H. The trifunctional antibody ertumaxomab destroys tumor cells that express low levels of human epidermal growth factor receptor 2. Cancer Res., 2009, 69(10), 4270-4276.
[126]
Portell, C.A.; Wenzell, C.M.; Advani, A.S. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin. Pharmacol., 2013, 5(Suppl. 1), 5-11.
[127]
Wolf, E.; Hofmeister, R.; Kufer, P.; Schlereth, B.; Baeuerle, P.A. BiTEs: Bispecific antibody constructs with unique anti-tumor activity. Drug Discov. Today, 2005, 10(18), 1237-1244.
[128]
Bargou, R.; Leo, E.; Zugmaier, G.; Klinger, M.; Goebeler, M.; Knop, S.; Noppeney, R.; Viardot, A.; Hess, G.; Schuler, M.; Einsele, H.; Brandl, C.; Wolf, A.; Kirchinger, P.; Klappers, P.; Schmidt, M.; Riethmüller, G.; Reinhardt, C.; Baeuerle, P.A.; Kufer, P. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science, 2008, 321(5891), 974-977.
[129]
Ribera, J.M.; Ferrer, A.; Ribera, J.; Genescà, E. Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia. OncoTargets Ther., 2015, 8, 1567-1574.
[130]
Stieglmaier, J.; Benjamin, J.; Nagorsen, D. Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer. Expert Opin. Biol. Ther., 2015, 15(8), 1093-1099.
[131]
Thakur, A.; Lum, L.G. ‘NextGen’ biologics: Bispecific antibodies and emerging clinical results. Expert Opin. Biol. Ther., 2016, 16(5), 675-688.
[132]
Ayyar, B.V.; Arora, S.; O’Kennedy, R. Coming-of-Age of Antibodies in Cancer Therapeutics. Trends Pharmacol. Sci., 2016, 37(12), 1009-1028.
[133]
Liu, L.; Lam, A.; Alderson, R.; Yang, Y.; Li, H.; Long, V.; Gorlatov, S.; Burke, S.; Ciccarone, V.; Nordstrom, J.; John-son, S.; Moore, P.; Bonvini, E. MGD011, humanized CD19 x CD3 DART® protein with enhanced pharmacokinetic properties, demonstrates potent T-cell mediated anti-tumor activity in preclinical models and durable B-cell depletion in cynomolgus monkeys following once-a-week dosing. Blood, 2014, 124, 1775.
[134]
Al-Hussaini, M.; Rettig, M.P.; Ritchey, J.K.; Karpova, D.; Uy, G.L.; Eissenberg, L.G.; Gao, F.; Eades, W.C.; Bonvini, E.; Chichili, G.R.; Moore, P.A.; Johnson, S.; Collins, L.; DiPersio, J.F. Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affinity retargeting platform. Blood, 2016, 127(1), 122-131.
[135]
Hurwitz, H.; Crocenzi, T.; Lohr, J.; Bonvini, E.; Johnson, S.; Moore, P.; Wigginton, J. A Phase I, first-in-human, open la-bel, dose escalation study of MGD007, a humanized gpA33 × CD3 dualaffinity retargeting (DART®) protein in patients with relapsed/refractory metastatic colorectal carcinoma. J. Immunother. Cancer, 2014, 2(Suppl. 3), 86.
[136]
Reusch, U.; Burkhardt, C.; Fucek, I.; Le Gall, F.; Le Gall, M.; Hoffmann, K.; Knackmuss, S.H.; Kiprijanov, S.; Little, M.; Zhukovsky, E.A. A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells. MAbs, 2014, 6(3), 728-739.
[137]
Rothe, A.; Sasse, S.; Topp, M.S.; Eichenauer, D.A.; Hummel, H.; Reiners, K.S.; Dietlein, M.; Kuhnert, G.; Kessler, J.; Buerkle, C.; Ravic, M.; Knackmuss, S.; Marschner, J.P.; Pogge von Strandmann, E.; Borchmann, P.; Engert, A. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood, 2015, 125(26), 4024-4031.
[138]
Reusch, U.; Duell, J.; Ellwanger, K.; Herbrecht, C.; Knackmuss, S.H.; Fucek, I.; Eser, M.; McAleese, F.; Molkenthin, V.; Gall, F.L.; Topp, M.; Little, M.; Zhukovsky, E.A. A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19(+) tumor cells. MAbs, 2015, 7(3), 584-604.
[139]
Hemmerle, T.; Wulhfard, S.; Neri, D. A critical evaluation of the tumor-targeting properties of bispecific antibodies based on quantitative biodistribution data. Protein Eng. Des. Sel., 2012, 25(12), 851-854.
[140]
Pasche, N.; Neri, D. Immunocytokines: A novel class of potent armed antibodies. Drug Discov. Today, 2012, 17(11-12), 583-590.
[141]
Gubbels, J.A.; Gadbaw, B.; Buhtoiarov, I.N.; Horibata, S.; Kapur, A.K.; Patel, D.; Hank, J.A.; Gillies, S.D.; Sondel, P.M.; Patankar, M.S.; Connor, J. Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface. Cancer Immunol. Immunother., 2011, 60(12), 1789-1800.
[142]
Catania, C.; Maur, M.; Berardi, R.; Rocca, A.; Giacomo, A.M.; Spitaleri, G.; Masini, C.; Pierantoni, C.; González-Iglesias, R.; Zigon, G.; Tasciotti, A.; Giovannoni, L.; Lovato, V.; Elia, G.; Menssen, H.D.; Neri, D.; Cascinu, S.; Conte, P.F.; Braud, Fd. The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer. Cell Adhes. Migr., 2015, 9(1-2), 14-21.
[143]
Gutbrodt, K.L.; Schliemann, C.; Giovannoni, L.; Frey, K.; Pabst, T.; Klapper, W.; Berdel, W.E.; Neri, D. Antibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia. Sci. Transl. Med., 2013, 5(201), 201ra118.
[144]
Schliemann, C.; Gutbrodt, K.L.; Kerkhoff, A.; Pohlen, M.; Wiebe, S.; Silling, G.; Angenendt, L.; Kessler, T.; Mesters, R.M.; Giovannoni, L.; Schäfers, M.; Altvater, B.; Rossig, C.; Grünewald, I.; Wardelmann, E.; Köhler, G.; Neri, D.; Stelljes, M.; Berdel, W.E. Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Cancer Immunol. Res., 2015, 3(5), 547-556.
[145]
Johannsen, M.; Spitaleri, G.; Curigliano, G.; Roigas, J.; Weikert, S.; Kempkensteffen, C.; Roemer, A.; Kloeters, C.; Rogalla, P.; Pecher, G.; Miller, K.; Berndt, A.; Kosmehl, H.; Trachsel, E.; Kaspar, M.; Lovato, V.; González-Iglesias, R.; Giovannoni, L.; Menssen, H.D.; Neri, D.; de Braud, F. The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma. Eur. J. Cancer, 2010, 46(16), 2926-2935.
[146]
Eigentler, T.K.; Weide, B.; de Braud, F.; Spitaleri, G.; Romanini, A.; Pflugfelder, A.; González-Iglesias, R.; Tasciotti, A.; Giovannoni, L.; Schwager, K.; Lovato, V.; Kaspar, M.; Trachsel, E.; Menssen, H.D.; Neri, D.; Garbe, C. A dose-escalation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine for the therapy of patients with metastatic melanoma. Clin. Cancer Res., 2011, 17(24), 7732-7742.
[147]
Weide, B.; Eigentler, T.K.; Pflugfelder, A.; Zelba, H.; Martens, A.; Pawelec, G.; Giovannoni, L.; Ruffini, P.A.; Elia, G.; Neri, D.; Gutzmer, R.; Becker, J.C.; Garbe, C. Intralesional treatment of stage III metastatic melanoma patients with L19-IL2 results in sustained clinical and systemic immunologic responses. Cancer Immunol. Res., 2014, 2(7), 668-678.
[148]
Schliemann, C.; Palumbo, A.; Zuberbühler, K.; Villa, A.; Kaspar, M.; Trachsel, E.; Klapper, W.; Menssen, H.D.; Neri, D. Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2. Blood, 2009, 113(10), 2275-2283.
[149]
Danielli, R.; Patuzzo, R.; Di Giacomo, A.M.; Gallino, G.; Maurichi, A.; Di Florio, A.; Cutaia, O.; Lazzeri, A.; Fazio, C.; Miracco, C.; Giovannoni, L.; Elia, G.; Neri, D.; Maio, M.; Santinami, M. Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study. Cancer Immunol. Immunother., 2015, 64(8), 999-1009.
[150]
Larson, S.M.; Carrasquillo, J.A.; Cheung, N.K.; Press, O.W. Radioimmunotherapy of human tumours. Nat. Rev. Cancer, 2015, 15(6), 347-360.
[151]
Goldenberg, D.M.; Sharkey, R.M.; Paganelli, G.; Barbet, J.; Chatal, J.F. Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy. J. Clin. Oncol., 2006, 24(5), 823-834.
[152]
Orcutt, K.D.; Slusarczyk, A.L.; Cieslewicz, M.; Ruiz-Yi, B.; Bhushan, K.R.; Frangioni, J.V.; Wittrup, K.D. Engineering an antibody with picomolar affinity to DOTA chelates of multiple radionuclides for pretargeted radioimmunotherapy and imaging. Nucl. Med. Biol., 2011, 38(2), 223-233.
[153]
Sharkey, R.M.; McBride, W.J.; Karacay, H.; Chang, K.; Griffiths, G.L.; Hansen, H.J.; Goldenberg, D.M. A universal pretargeting system for cancer detection and therapy using bispecific antibody. Cancer Res., 2003, 63(2), 354-363.
[154]
Orcutt, K.D.; Ackerman, M.E.; Cieslewicz, M.; Quiroz, E.; Slusarczyk, A.L.; Frangioni, J.V.; Wittrup, K.D. A modular IgG-scFv bispecific antibody topology. Protein Eng. Des. Sel., 2010, 23(4), 221-228.
[155]
Cheal, S.M.; Xu, H.; Guo, H.F.; Zanzonico, P.B.; Larson, S.M.; Cheung, N.K. Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using an IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex. Mol. Cancer Ther., 2014, 13(7), 1803-1812.
[156]
Allen, T.M. Ligand-targeted therapeutics in anticancer therapy. Nat. Rev. Cancer, 2002, 2(10), 750-763.
[157]
Schindler, J.; Sausville, E.; Messmann, R.; Uhr, J.W.; Vitetta, E.S. The toxicity of deglycosylated ricin A chain-containing immunotoxins in patients with non-Hodgkin’s lymphoma is exacerbated by prior radiotherapy: A retrospective analysis of patients in five clinical trials. Clin. Cancer Res., 2001, 7(2), 255-258.
[158]
Kowalski, M.; Guindon, J.; Brazas, L.; Moore, C.; Entwistle, J.; Cizeau, J.; Jewett, M.A.; MacDonald, G.C. A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Guérin. J. Urol., 2012, 188(5), 1712-1718.
[159]
Borghaei, H.; Alpaugh, K.; Hedlund, G.; Forsberg, G.; Langer, C.; Rogatko, A.; Hawkins, R.; Dueland, S.; Lassen, U.; Cohen, R.B. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer. J. Clin. Oncol., 2009, 27(25), 4116-4123.
[160]
Eisen, T.; Hedlund, G.; Forsberg, G.; Hawkins, R. Naptumomab estafenatox: Targeted immunotherapy with a novel immunotoxin. Curr. Oncol. Rep., 2014, 16(2), 370.
[161]
Chandramohan, V.; Bigner, D.D. A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma. OncoImmunology, 2013, 2(12), e26852.
[162]
Garnett, M.C. Targeted drug conjugates: principles and progress. Adv. Drug Deliv. Rev., 2001, 53(2), 171-216.
[163]
Kim, E.G.; Kim, K.M. Strategies and advancement in anti-body-drug conjugate optimization for targeted cancer thera-peutics. Biomol. Ther. (Seoul), 2015, 23(6), 493-509.
[164]
Kim, K.M.; McDonagh, C.F.; Westendorf, L.; Brown, L.L.; Sussman, D.; Feist, T.; Lyon, R.; Alley, S.C.; Okeley, N.M.; Zhang, X.; Thompson, M.C.; Stone, I.; Gerber, H.P.; Carter, P.J. Anti-CD30 diabody-drug conjugates with potent antitumor activity. Mol. Cancer Ther., 2008, 7(8), 2486-2497.
[165]
Richards, D.A.; Maruani, A.; Chudasama, V. Antibody fragments as nanoparticle targeting ligands: a step in the right direction. Chem. Sci. (Camb.), 2017, 8(1), 63-77.
[166]
Shargh, V.H.; Hondermarck, H.; Liang, M. Antibody-targeted biodegradable nanoparticles for cancer therapy. Nanomedicine (Lond.), 2016, 11(1), 63-79.
[167]
Wang, W.; Wang, E.Q.; Balthasar, J.P. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin. Pharmacol. Ther., 2008, 84(5), 548-558.
[168]
Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol., 2007, 2(12), 751-760.
[169]
Cheng, W.W.; Allen, T.M. Targeted delivery of anti-CD19 liposomal doxorubicin in B-cell lymphoma: A comparison of whole monoclonal antibody, Fab’ fragments and single chain Fv. J. Control. Release, 2008, 126(1), 50-58.
[170]
Sapra, P.; Moase, E.H.; Ma, J.; Allen, T.M. Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab’ fragments. Clin. Cancer Res., 2004, 10(3), 1100-1111.
[171]
Miller, K.; Cortes, J.; Hurvitz, S.A.; Krop, I.E.; Tripathy, D.; Verma, S.; Riahi, K.; Reynolds, J.G.; Wickham, T.J.; Molnar, I.; Yardley, D.A. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer, 2016, 16, 352.
[172]
Xiangbao, Y.; Linquan, W.; Mingwen, H.; Fan, Z.; Kai, W.; Xin, Y.; Kaiyang, W.; Huaqun, F. Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles, an antibody conjugate with potent and selective anti-hepatocellular carcinoma activity. Biomed. Pharmacother., 2014, 68(5), 597-602.
[173]
Quarta, A.; Bernareggi, D.; Benigni, F.; Luison, E.; Nano, G.; Nitti, S.; Cesta, M.C.; Di Ciccio, L.; Canevari, S.; Pellegrino, T.; Figini, M. Targeting FR-expressing cells in ovarian cancer with Fab-functionalized nanoparticles: A full study to provide the proof of principle from in vitro to in vivo. Nanoscale, 2015, 7(6), 2336-2351.
[174]
Rabenhold, M.; Steiniger, F.; Fahr, A.; Kontermann, R.E.; Rüger, R. Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and fibroblast activation protein (FAP) simultaneously. J. Control. Release, 2015, 201, 56-67.
[175]
Iden, D.L.; Allen, T.M. In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach. Biochim. Biophys. Acta, 2001, 1513(2), 207-216.
[176]
Li, W.M.; Mayer, L.D.; Bally, M.B. Prevention of antibody-mediated elimination of ligand-targeted liposomes by using poly(ethylene glycol)-modified lipids. J. Pharmacol. Exp. Ther., 2002, 300(3), 976-983.
[177]
Ludwig, D.L.; Pereira, D.S.; Zhu, Z.; Hicklin, D.J.; Bohlen, P. Monoclonal antibody therapeutics and apoptosis. Oncogene, 2003, 22(56), 9097-9106.
[178]
Reichert, J.M.; Rosensweig, C.J.; Faden, L.B.; Dewitz, M.C. Monoclonal antibody successes in the clinic. Nat. Biotechnol., 2005, 23(9), 1073-1078.
[179]
Adams, G.P.; Weiner, L.M. Monoclonal antibody therapy of cancer. Nat. Biotechnol., 2005, 23(9), 1147-1157.
[180]
Salomon, D.S.; Brandt, R.; Ciardiello, F.; Normanno, N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol., 1995, 19(3), 183-232.
[181]
Polanovski, O.L.; Lebedenko, E.N.; Deyev, S.M. ERBB oncogene proteins as targets for monoclonal antibodies. Biochemistry (Mosc.), 2012, 77(3), 227-245.
[182]
Rocha-Lima, C.M.; Soares, H.P.; Raez, L.E.; Singal, R. EGFR targeting of solid tumors. Cancer Contr., 2007, 14(3), 295-304.
[183]
Mendelsohn, J. Blockade of receptors for growth factors: an anticancer therapy--the fourth annual Joseph H Burchenal American Association of Cancer Research Clinical Research Award Lecture. Clin. Cancer Res., 2000, 6(3), 747-753.
[184]
Keating, G.M. Panitumumab: a review of its use in metastatic colorectal cancer. Drugs, 2010, 70(8), 1059-1078.
[185]
Mandal, M.; Adam, L.; Mendelsohn, J.; Kumar, R. Nuclear targeting of Bax during apoptosis in human colorectal cancer cells. Oncogene, 1998, 17(8), 999-1007.
[186]
Tortora, G.; Caputo, R.; Pomatico, G.; Pepe, S.; Bianco, A.R.; Agrawal, S.; Mendelsohn, J.; Ciardiello, F. Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth. Clin. Cancer Res., 1999, 5(4), 875-881.
[187]
Reichert, J.M.; Dhimolea, E. The future of antibodies as cancer drugs. Drug Discov. Today, 2012, 17(17-18), 954-963.
[188]
Slamon, D.J.; Clark, G.M.; Wong, S.G.; Levin, W.J.; Ullrich, A.; McGuire, W.L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987, 235(4785), 177-182.
[189]
Hynes, N.E.; Lane, H.A. ERBB receptors and cancer: The complexity of targeted inhibitors. Nat. Rev. Cancer, 2005, 5(5), 341-354.
[190]
Cho, H.S.; Mason, K.; Ramyar, K.X.; Stanley, A.M.; Gabelli, S.B.; Denney, D.W., Jr; Leahy, D.J. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature, 2003, 421(6924), 756-760.
[191]
Agus, D.B.; Akita, R.W.; Fox, W.D.; Lewis, G.D.; Higgins, B.; Pisacane, P.I.; Lofgren, J.A.; Tindell, C.; Evans, D.P.; Maiese, K.; Scher, H.I.; Sliwkowski, M.X. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell, 2002, 2(2), 127-137.
[192]
Leung, K.M.; Batey, S.; Rowlands, R.; Isaac, S.J.; Jones, P.; Drewett, V.; Carvalho, J.; Gaspar, M.; Weller, S.; Medcalf, M.; Wydro, M.M.; Pegram, R.; Mudde, G.C.; Bauer, A.; Moulder, K.; Woisetschläger, M.; Tuna, M.; Haurum, J.S.; Sun, H. HER2-specific modified Fc fragment (Fcab) in-duces antitumor effects through degradation of HER2 and apoptosis. Mol. Ther., 2015, 23(11), 1722-1733.
[193]
Riedl, S.J.; Shi, Y. Molecular mechanisms of caspase regulation during apoptosis. Nat. Rev. Mol. Cell Biol., 2004, 5(11), 897-907.
[194]
de Miguel, D.; Lemke, J.; Anel, A.; Walczak, H.; Martinez-Lostao, L. Onto better TRAILs for cancer treatment. Cell Death Differ., 2016, 23(5), 733-747.
[195]
Liu, F.; Si, Y.; Liu, G.; Li, S.; Zhang, J.; Ma, Y. The tetravalent anti-DR5 antibody without cross-linking direct induces apoptosis of cancer cells. Biomed. Pharmacother., 2015, 70, 41-45.
[196]
Chuntharapai, A.; Dodge, K.; Grimmer, K.; Schroeder, K.; Marsters, S.A.; Koeppen, H.; Ashkenazi, A.; Kim, K.J. Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4. J. Immunol., 2001, 166(8), 4891-4898.
[197]
Dobson, C.L.; Main, S.; Newton, P.; Chodorge, M.; Cadwallader, K.; Humphreys, R.; Albert, V.; Vaughan, T.J.; Minter, R.R.; Edwards, B.M. Human monomeric antibody fragments to TRAIL-R1 and TRAIL-R2 that display potent in vitro agonism. MAbs, 2009, 1(6), 552-562.
[198]
Cheng, X.; Meng, Q.; Gao, C.; Zhuang, G.; Huang, X.; Zhang, J.; Liu, B.; Fan, X.; Zhang, M. Analysis of aDR5scFv with specific identification and function. Monoclon. Antib. Immunodiagn. Immunother., 2016, 35(1), 25-31.
[199]
Wang, W.; He, W.; Wang, L.; Zhang, G.; Gao, B. Pentamerisation of a scFv directed against TRAIL receptor 2 increases its antitumour efficacy. Immunol. Cell Biol., 2013, 91(5), 360-367.
[200]
Stieglmaier, J.; Bremer, E.; Kellner, C.; Liebig, T.M.; ten Cate, B.; Peipp, M.; Schulze-Koops, H.; Pfeiffer, M.; Bühring, H.J.; Greil, J.; Oduncu, F.; Emmerich, B.; Fey, G.H.; Helfrich, W. Selective induction of apoptosis in leukemic B-lymphoid cells by a CD19-specific TRAIL fusion protein. Cancer Immunol. Immunother., 2008, 57(2), 233-246.
[201]
Yan, C.; Li, S.; Li, Z.; Peng, H.; Yuan, X.; Jiang, L.; Zhang, Y.; Fan, D.; Hu, X.; Yang, M.; Xiong, D. Human umbilical cord mesenchymal stem cells as vehicles of CD20-specific TRAIL fusion protein delivery: A double-target therapy against non-Hodgkin’s lymphoma. Mol. Pharm., 2013, 10(1), 142-151.
[202]
ten Cate, B.; Bremer, E.; de Bruyn, M.; Bijma, T.; Samplonius, D.; Schwemmlein, M.; Huls, G.; Fey, G.; Helfrich, W. A novel AML-selective TRAIL fusion protein that is superior to Gemtuzumab Ozogamicin in terms of in vitro selectivity, activity and stability. Leukemia, 2009, 23(8), 1389-1397.
[203]
Schneider, B.; Münkel, S.; Krippner-Heidenreich, A.; Grunwald, I.; Wels, W.S.; Wajant, H.; Pfizenmaier, K.; Gerspach, J. Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins. Cell Death Dis., 2010, 1, e68.
[204]
Siegemund, M.; Pollak, N.; Seifert, O.; Wahl, K.; Hanak, K.; Vogel, A.; Nussler, A.K.; Göttsch, D.; Münkel, S.; Bantel, H.; Kontermann, R.E.; Pfizenmaier, K. Superior antitumoral activity of dimerized targeted single-chain TRAIL fusion proteins under retention of tumor selectivity. Cell Death Dis., 2012, 3, e295.
[205]
de Bruyn, M.; Wei, Y.; Wiersma, V.R.; Samplonius, D.F.; Klip, H.G.; van der Zee, A.G.; Yang, B.; Helfrich, W.; Bremer, E. Cell surface delivery of TRAIL strongly augments the tumoricidal activity of T cells. Clin. Cancer Res., 2011, 17(17), 5626-5637.
[206]
El-Mesery, M.; Trebing, J.; Schäfer, V.; Weisenberger, D.; Siegmund, D.; Wajant, H. CD40-directed scFv-TRAIL fusion proteins induce CD40-restricted tumor cell death and activate dendritic cells. Cell Death Dis., 2013, 4(11), e916.
[207]
Zhu, Y.; Choi, S.H.; Shah, K. Multifunctional receptor-targeting antibodies for cancer therapy. Lancet Oncol., 2015, 16(15), e543-e554.
[208]
Byrd, J.C.; Kitada, S.; Flinn, I.W.; Aron, J.L.; Pearson, M.; Lucas, D.; Reed, J.C. The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction. Blood, 2002, 99(3), 1038-1043.
[209]
Alas, S.; Ng, C.P.; Bonavida, B. Rituximab modifies the cisplatin-mitochondrial signaling pathway, resulting in apoptosis in cisplatin-resistant non-Hodgkin’s lymphoma. Clin. Cancer Res., 2002, 8(3), 836-845.
[210]
Liu, Y.X.; Xiong, D.S.; Fan, D.M.; Xu, Y.F.; Yang, C.Z. Apoptosis of Raji cells by an anti-CD20 antibody HI47 and its fragments. Leuk. Res., 2004, 28(2), 209-211.
[211]
Cardarelli, P.M.; Quinn, M.; Buckman, D.; Fang, Y.; Colcher, D.; King, D.J.; Bebbington, C.; Yarranton, G. Binding to CD20 by anti-B1 antibody or F(ab’)(2) is sufficient for induction of apoptosis in B-cell lines. Cancer Immunol. Immunother., 2002, 51(1), 15-24.
[212]
Liu, Y.; Zheng, M.; Lai, Z.; Xiong, D.; Fan, D.; Xu, Y.; Peng, H.; Shao, X.; Xu, Y.; Yang, M.; Wang, J.; Liu, H.; Xie, Y.; Yang, C.; Zhu, Z. Inhibition of human B-cell lymphoma by an anti-CD20 antibody and its chimeric F(ab’)2 fragment via induction of apoptosis. Cancer Lett., 2004, 205(2), 143-153.
[213]
Bremer, E.; ten Cate, B.; Samplonius, D.F.; Mueller, N.; Wajant, H.; Stel, A.J.; Chamuleau, M.; van de Loosdrecht, A.A.; Stieglmaier, J.; Fey, G.H.; Helfrich, W. Superior activity of fusion protein scFvRit: sFasL over cotreatment with rituximab and Fas agonists. Cancer Res., 2008, 68(2), 597-604.
[214]
Mateo, V.; Lagneaux, L.; Bron, D.; Biron, G.; Armant, M.; Delespesse, G.; Sarfati, M. CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia. Nat. Med., 1999, 5(11), 1277-1284.
[215]
Roué, G.; Bitton, N.; Yuste, V.J.; Montange, T.; Rubio, M.; Dessauge, F.; Delettre, C.; Merle-Béral, H.; Sarfati, M.; Susin, S.A. Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release. Biochimie, 2003, 85(8), 741-746.
[216]
Kikuchi, Y.; Uno, S.; Kinoshita, Y.; Yoshimura, Y.; Iida, S.; Wakahara, Y.; Tsuchiya, M.; Yamada-Okabe, H.; Fukushima, N. Apoptosis inducing bivalent single-chain antibody fragments against CD47 showed antitumor potency for multiple myeloma. Leuk. Res., 2005, 29(4), 445-450.
[217]
Sagawa, M.; Shimizu, T.; Fukushima, N.; Kinoshita, Y.; Ohizumi, I.; Uno, S.; Kikuchi, Y.; Ikeda, Y.; Yamada-Okabe, H.; Kizaki, M. A new disulfide-linked dimer of a single-chain antibody fragment against human CD47 induces apoptosis in lymphoid malignant cells via the hypoxia inducible factor-1α pathway. Cancer Sci., 2011, 102(6), 1208-1215.
[218]
Ahmed, M.; Cheung, N.K. Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. FEBS Lett., 2014, 588(2), 288-297.
[219]
Cheever, M.A.; Allison, J.P.; Ferris, A.S.; Finn, O.J.; Hastings, B.M.; Hecht, T.T.; Mellman, I.; Prindiville, S.A.; Viner, J.L.; Weiner, L.M.; Matrisian, L.M. The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res., 2009, 15(17), 5323-5337.
[220]
Doronin, I.I.; Vishnyakova, P.A.; Kholodenko, I.V.; Ponomarev, E.D.; Ryazantsev, D.Y.; Molotkovskaya, I.M.; Kholodenko, R.V. Ganglioside GD2 in reception and transduction of cell death signal in tumor cells. BMC Cancer, 2014, 14, 295.
[221]
Mora, J. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma. Expert Rev. Clin. Pharmacol., 2016, 9(5), 647-653.
[222]
Brown, B.S.; Patanam, T.; Mobli, K.; Celia, C.; Zage, P.E.; Bean, A.J.; Tasciotti, E. Etoposide-loaded immunoliposomes as active targeting agents for GD2-positive malignancies. Cancer Biol. Ther., 2014, 15(7), 851-861.
[223]
Brignole, C.; Pastorino, F.; Marimpietri, D.; Pagnan, G.; Pistorio, A.; Allen, T.M.; Pistoia, V.; Ponzoni, M. Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. J. Natl. Cancer Inst., 2004, 96(15), 1171-1180.
[224]
Di Paolo, D.; Ambrogio, C.; Pastorino, F.; Brignole, C.; Martinengo, C.; Carosio, R.; Loi, M.; Pagnan, G.; Emionite, L.; Cilli, M.; Ribatti, D.; Allen, T.M.; Chiarle, R.; Ponzoni, M.; Perri, P. Selective therapeutic targeting of the anaplastic lymphoma kinase with liposomal siRNA induces apoptosis and inhibits angiogenesis in neuroblastoma. Mol. Ther., 2011, 19(12), 2201-2212.
[225]
Baiu, D.C.; Artz, N.S.; McElreath, M.R.; Menapace, B.D.; Hernando, D.; Reeder, S.B.; Grüttner, C.; Otto, M. High specificity targeting and detection of human neuroblastoma using multifunctional anti-GD2 iron-oxide nanoparticles. Nanomedicine (Lond.), 2015, 10(19), 2973-2988.
[226]
Tivnan, A.; Orr, W.S.; Gubala, V.; Nooney, R.; Williams, D.E.; McDonagh, C.; Prenter, S.; Harvey, H.; Domingo-Fernández, R.; Bray, I.M.; Piskareva, O.; Ng, C.Y.; Lode, H.N.; Davidoff, A.M.; Stallings, R.L. Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One, 2012, 7(5), e38129.
[227]
Pastorino, F.; Brignole, C.; Loi, M.; Di Paolo, D.; Di Fiore, A.; Perri, P.; Pagnan, G.; Ponzoni, M. Nanocarrier-mediated targeting of tumor and tumor vascular cells improves uptake and penetration of drugs into neuroblastoma. Front. Oncol., 2013, 3, 190.
[228]
Zubareva, A.A.; Boyko, A.A.; Kholodenko, I.V.; Rozov, F.N.; Larina, M.V.; Aliev, T.K.; Doronin, I.I.; Vishnyakova, P.A.; Molotkovskaya, I.M.; Kholodenko, R.V. Chitosan na-noparticles targeted to the tumor-associated ganglioside GD2. Russ. J. Bioorganic Chem., 2016, 42, 532.
[229]
Zeng, Y.; Huebener, N.; Fest, S.; Weixler, S.; Schroeder, U.; Gaedicke, G.; Xiang, R.; Schramm, A.; Eggert, A.; Reisfeld, R.A.; Lode, H.N. Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. Cancer Res., 2007, 67(5), 2331-2338.
[230]
Otto, M.; Barfield, R.C.; Martin, W.J.; Iyengar, R.; Leung, W.; Leimig, T.; Chaleff, S.; Gillies, S.D.; Handgretinger, R. Combination immunotherapy with clinical-scale enriched human gammadelta T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma. Clin. Cancer Res., 2005, 11(23), 8486-8491.
[231]
Wargalla, U.C.; Reisfeld, R.A. Rate of internalization of an immunotoxin correlates with cytotoxic activity against human tumor cells. Proc. Natl. Acad. Sci. USA, 1989, 86(13), 5146-5150.
[232]
Mujoo, K.; Reisfeld, R.A.; Cheung, L.; Rosenblum, M.G. A potent and specific immunotoxin for tumor cells expressing disialoganglioside GD2. Cancer Immunol. Immunother., 1991, 34(3), 198-204.
[233]
Thomas, P.B.; Delatte, S.J.; Sutphin, A.; Frankel, A.E.; Tagge, E.P. Effective targeted cytotoxicity of neuroblastoma cells. J. Pediatr. Surg., 2002, 37(3), 539-544.
[234]
Tur, M.K.; Sasse, S.; Stöcker, M.; Djabelkhir, K.; Huhn, M.; Matthey, B.; Gottstein, C.; Pfitzner, T.; Engert, A.; Barth, S. An anti-GD2 single chain Fv selected by phage display and fused to Pseudomonas exotoxin A develops specific cytotoxic activity against neuroblastoma derived cell lines. Int. J. Mol. Med., 2001, 8(5), 579-584.
[235]
Modak, S.; Cheung, N.K. Antibody-based targeted radiation to pediatric tumors. J. Nucl. Med., 2005, 46(Suppl. 1), 157S-163S.
[236]
Perez Horta, Z.; Goldberg, J.L.; Sondel, P.M. Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy. Immunotherapy, 2016, 8(9), 1097-1117.
[237]
Louis, C.U.; Savoldo, B.; Dotti, G.; Pule, M.; Yvon, E.; Myers, G.D.; Rossig, C.; Russell, H.V.; Diouf, O.; Liu, E.; Liu, H.; Wu, M.F.; Gee, A.P.; Mei, Z.; Rooney, C.M.; Heslop, H.E.; Brenner, M.K. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood, 2011, 118(23), 6050-6056.
[238]
Yankelevich, M.; Kondadasula, S.V.; Thakur, A.; Buck, S.; Cheung, N.K.; Lum, L.G. Anti-CD3 × anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets. Pediatr. Blood Cancer, 2012, 59(7), 1198-1205.
[239]
Cheng, M.; Santich, B.H.; Xu, H.; Ahmed, M.; Huse, M.; Cheung, N.K. Successful engineering of a highly potent single-chain variable-fragment (scFv) bispecific antibody to target disialoganglioside (GD2) positive tumors. OncoImmunology, 2016, 5(6), e1168557.
[240]
Yoshida, S.; Fukumoto, S.; Kawaguchi, H.; Sato, S.; Ueda, R.; Furukawa, K.; Ganglioside, G.; Ganglioside, G. D2) in small cell lung cancer cell lines: enhancement of cell proliferation and mediation of apoptosis. Cancer Res., 2001, 61(10), 4244-4252.
[241]
Kowalczyk, A.; Gil, M.; Horwacik, I.; Odrowaz, Z.; Kozbor, D.; Rokita, H. The GD2-specific 14G2a monoclonal antibody induces apoptosis and enhances cytotoxicity of chemotherapeutic drugs in IMR-32 human neuroblastoma cells. Cancer Lett., 2009, 281(2), 171-182.
[242]
Aixinjueluo, W.; Furukawa, K.; Zhang, Q.; Hamamura, K.; Tokuda, N.; Yoshida, S.; Ueda, R.; Furukawa, K. Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: Roles of anoikis. J. Biol. Chem., 2005, 280(33), 29828-29836.
[243]
Vishnyakova, P.A.; Doronin, I.I.; Kholodenko, I.V.; Rya-zantsev, D.Y.; Molotkovskaya, I.M.; Kholodenko, R.V. Caspases participation in the cell death, induced by GD2-specific monoclonal antibody. Bioorg. Khim., 2014, 40, 1-10.
[244]
Horwacik, I.; Rokita, H. Targeting of tumor-associated gangliosides with antibodies affects signaling pathways and leads to cell death including apoptosis. Apoptosis, 2015, 20(5), 679-688.
[245]
Tsao, C.Y.; Sabbatino, F.; Cheung, N.K.; Hsu, J.C.; Villani, V.; Wang, X.; Ferrone, S. Anti-proliferative and pro-apoptotic activity of GD2 ganglioside-specific monoclonal antibody 3F8 in human melanoma cells. OncoImmunology, 2015, 4(8), e1023975.
[246]
Sorkin, L.S.; Otto, M.; Baldwin, W.M., III; Vail, E.; Gillies, S.D.; Handgretinger, R.; Barfield, R.C.; Ming , Yu. H.; Yu, A.L. Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia. Pain, 2010, 149(1), 135-142.
[247]
Cochonneau, D.; Terme, M.; Michaud, A.; Dorvillius, M.; Gautier, N.; Frikeche, J.; Alvarez-Rueda, N.; Bougras, G.; Aubry, J.; Paris, F.; Birklé, S. Cell cycle arrest and apoptosis induced by O-acetyl-GD2-specific monoclonal antibody 8B6 inhibits tumor growth in vitro and in vivo. Cancer Lett., 2013, 333(2), 194-204.
[248]
Doronin, I.I.; Kholodenko, I.V.; Molotkovskaya, I.M.; Kholodenko, R.V. Preparation of Fab-fragments of GD2-specific antibodies and analysis of their antitumor activity in vitro. Bull. Exp. Biol. Med., 2013, 154(5), 658-663.
[249]
Kholodenko, I.V.; Doronin, I.I.; Vishnyakova, P.A.; Bolkhovitina, E.L.; Molotkovskaya, I.M.; Kholodenko, R.V. Antitumor activity of GD2-specific antibodies and their Fab-fragments in the mouse tumor model. Immunologiya (Russia), 2013, 34, 199-203.
[250]
Strohl, W.R.; Strohl, L.M. Therapeutic antibody engineering: Current and future advances driving the strongest growth area in the pharmaceutical industry 2012. 11
[251]
Jawa, V.; Cousens, L.; De Groote, A.S. Immunogenicity of therapeutic fusion proteins: Contributory factors and clinical experience Fusion protein technolo-gies for biopharmaceuticals: applications and challenges, 2013. 150-175
[252]
Boder, E.T.; Midelfort, K.S.; Wittrup, K.D. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc. Natl. Acad. Sci. USA, 2000, 97(20), 10701-10705.
[253]
Rader, C. Overview on concepts and applications of Fab antibody fragments.. Curr. Protoc. Protein Sci; , 2009. Chapter 6, Unit 6.9
[254]
Strohl, W.R. Fusion proteins for half-life extension of bio-logics as a strategy to make biobetters. BioDrugs, 2015, 29(4), 215-239.
[255]
Chapman, A.P.; Antoniw, P.; Spitali, M.; West, S.; Stephens, S.; King, D.J. Therapeutic antibody fragments with prolonged in vivo half-lives. Nat. Biotechnol., 1999, 17(8), 780-783.
[256]
Kontermann, R.E. Strategies to extend plasma half-lives of recombinant antibodies. BioDrugs, 2009, 23(2), 93-109.
[257]
Werle, M.; Bernkop-Schnürch, A. Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids, 2006, 30(4), 351-367.
[258]
Chapman, A.P. PEGylated antibodies and antibody fragments for improved therapy: A review. Adv. Drug Deliv. Rev., 2002, 54(4), 531-545.
[259]
Jevsevar, S.; Kunstelj, M.; Porekar, V.G. PEGylation of therapeutic proteins. Biotechnol. J., 2010, 5(1), 113-128.
[260]
Schlapschy, M.; Binder, U.; Börger, C.; Theobald, I.; Wachinger, K.; Kisling, S.; Haller, D.; Skerra, A. PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins. Protein Eng. Des. Sel., 2013, 26(8), 489-501.
[261]
Schellenberger, V.; Wang, C.W.; Geething, N.C.; Spink, B.J.; Campbell, A.; To, W.; Scholle, M.D.; Yin, Y.; Yao, Y.; Bogin, O.; Cleland, J.L.; Silverman, J.; Stemmer, W.P. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat. Biotechnol., 2009, 27(12), 1186-1190.
[262]
Mishraa, P.; Nayakb, B.; Deya, R.K. PEGylation in anti-cancer therapy: An overview. Asian. J. Pharm. Sci., 2016, 11(3), 337-348.
[263]
Rudmann, D.G.; Alston, J.T.; Hanson, J.C.; Heidel, S. High molecular weight polyethylene glycol cellular distribution and PEG-associated cytoplasmic vacuolation is molecular weight dependent and does not require conjugation to proteins. Toxicol. Pathol., 2013, 41(7), 970-983.
[264]
Davé, E.; Adams, R.; Zaccheo, O.; Carrington, B.; Compson, J.E.; Dugdale, S.; Airey, M.; Malcolm, S.; Hailu, H.; Wild, G.; Turner, A.; Heads, J.; Sarkar, K.; Ventom, A.; Marshall, D.; Jairaj, M.; Kopotsha, T.; Christodoulou, L.; Zamacona, M.; Lawson, A.D.; Heywood, S.; Humphreys, D.P. Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding. MAbs, 2016, 8(7), 1319-1335.
[265]
Adams, R.; Griffin, L.; Compson, J.E.; Jairaj, M.; Baker, T.; Ceska, T.; West, S.; Zaccheo, O.; Davé, E.; Lawson, A.D.; Humphreys, D.P.; Heywood, S. Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life. MAbs, 2016, 8(7), 1336-1346.
[266]
Czajkowsky, D.M.; Hu, J.; Shao, Z.; Pleass, R.J. Fc-fusion proteins: New developments and future perspectives. EMBO Mol. Med., 2012, 4(10), 1015-1028.
[267]
Hutt, M.; Färber-Schwarz, A.; Unverdorben, F.; Richter, F.; Kontermann, R.E. Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains. J. Biol. Chem., 2012, 287(7), 4462-4469.
[268]
Nguyen, A.; Reyes, A.E., II; Zhang, M.; McDonald, P.; Wong, W.L.; Damico, L.A.; Dennis, M.S. The pharmacokinetics of an albumin-binding Fab (AB.Fab) can be modulated as a function of affinity for albumin. Protein Eng. Des. Sel., 2006, 19(7), 291-297.
[269]
Andersen, J.T.; Cameron, J.; Plumridge, A.; Evans, L.; Sleep, D.; Sandlie, I. Single-chain variable fragment albumin fusions bind the neonatal Fc receptor (FcRn) in a species-dependent manner: implications for in vivo half-life evaluation of albumin fusion therapeutics. J. Biol. Chem., 2013, 288(33), 24277-24285.
[270]
Tijink, B.M.; Laeremans, T.; Budde, M.; Stigter-van Walsum, M.; Dreier, T.; de Haard, H.J.; Leemans, C.R.; van Dongen, G.A. Improved tumor targeting of anti-epidermal growth factor receptor nanobodies through albumin binding: Taking advantage of modular nanobody technology. Mol. Cancer Ther., 2008, 7(8), 2288-2297.
[271]
Müller, D.; Karle, A.; Meissburger, B.; Höfig, I.; Stork, R.; Kontermann, R.E. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. J. Biol. Chem., 2007, 282(17), 12650-12660.
[272]
Kenanova, V.E.; Olafsen, T.; Salazar, F.B.; Williams, L.E.; Knowles, S.; Wu, A.M. Tuning the serum persistence of human serum albumin domain III: Diabody fusion proteins. Protein Eng. Des. Sel., 2010, 23(10), 789-798.
[273]
Sleep, D.; Cameron, J.; Evans, L.R. Albumin as a versatile platform for drug half-life extension. Biochim. Biophys. Acta, 2013, 1830(12), 5526-5534.
[274]
Zhao, S.; Zhang, Y.; Tian, H.; Chen, X.; Cai, D.; Yao, W.; Gao, X. Extending the serum half-life of G-CSF via fusion with the domain III of human serum albumin. BioMed Res. Int., 2013, 2013, 107238.
[275]
Podust, V.N.; Balan, S.; Sim, B.C.; Coyle, M.P.; Ernst, U.; Peters, R.T.; Schellenberger, V. Extension of in vivo half-life of biologically active molecules by XTEN protein polymers. J. Control. Release, 2016, 240, 52-66.
[276]
Floss, D.M.; Schallau, K.; Rose-John, S.; Conrad, U.; Scheller, J. Elastin-like polypeptides revolutionize recombinant protein expression and their biomedical application. Trends Biotechnol., 2010, 28(1), 37-45.
[277]
Yuen, K.C.; Conway, G.S.; Popovic, V.; Merriam, G.R.; Bailey, T.; Hamrahian, A.H.; Biller, B.M.; Kipnes, M.; Moore, J.A.; Humphriss, E.; Bright, G.M.; Cleland, J.L. A long-acting human growth hormone with delayed clearance (VRS-317): Results of a double-blind, placebo-controlled, single ascending dose study in growth hormone-deficient adults. J. Clin. Endocrinol. Metab., 2013, 98(6), 2595-2603.
[278]
Cleland, J.L.; Silverman, J.; Wang, C-W.; Geething, N.; Spink, B.; Campbell, A.; To, W.; Scholle, M.D.; Yin, Y.; Yao, Y.; Stemmer, W.P.C.; Schellenberger, V. An extended halflife exenatide construct for weekly administration in the treatment of diabetes mellitus. 2009. American Diabetes Association 69th Scientific Sessions New Orleans, LA.

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