Title:Specific Targeting of Zinc Transporter LIV-1 with Immunocytokine
Containing Anti-LIV-1 VHH and Human IL-2 and Evaluation of its In vitro
Antitumor Activity
Volume: 30
Issue: 11
Author(s): Rada Dehghan, Arezoo Beig Parikhani, Reza Ahangari Cohan, Mohammad Ali Shokrgozar, Esmat Mirabzadeh, Soheila Ajdary, Sirous Zeinali, Hajarossadat Ghaderi, Yeganeh Talebkhan*Mahdi Behdani*
Affiliation:
- Department of Medical
Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
- Venom and Biotherapeutics Molecules Laboratory, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur
Institute of Iran, Tehran, Iran
Keywords:
Immunotherapy, interleukin-2, immunocytokine, LIV-1, nanobody, pharmacokinetics.
Abstract:
Background: Interleukin 2 (IL-2) is a vital cytokine in the induction of T and NK cell responses,
the proliferation of CD8+ T cells, and the effective treatment of human cancers such as melanoma and renal
cell carcinoma. However, widespread use of this cytokine is limited due to its short half-life, severe toxicity,
lack of specific tumor targeting, and activation of Treg cells mediated by high-affinity interleukin-2 receptors.
Objective: In this study, a tumor-targeting LIV-1 VHH-mutIL2 immunocytokine with reduced CD25 (α chain
of the high-affinity IL-2 receptor) binding activity was developed to improve IL-2 half-life by decreasing its renal
infiltration in comparison with wild and mutant IL-2 molecules.
Methods: The recombinant immunocytokine was designed and expressed. The biological activity of the purified
fusion protein was investigated in in vitro and in vivo experiments.
Results: The fusion protein represented specific binding to MCF7 (the breast cancer cell line) and more efficient
cytotoxicity than wild-type IL-2 and mutant IL-2. The PK parameters of the recombinant immunocytokine
were also improved in comparison to the IL-2 molecules.
Conclusion: The observed results showed that LIV1-mIL2 immunocytokine could be considered as an effective
agent in the LIV-1-targeted treatment of cancers due to its longer half-life and stronger cytotoxicity.
