Title:Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases
Volume: 17
Issue: 32
Author(s): Mario E.G. Moral and Teruna J. Siahaan*
Affiliation:
- Department of Pharmaceutical Chemistry, The University of Kansas, Simons Laboratory, 2095 Constant Ave., Lawrence, Kansas 66047,United States
Keywords:
Antigenic peptide, autoimmune disease, Bifunctional Peptide Inhibitor (BPI), cell adhesion, ICAM-1, Immunological
synapse, Integrin, LFA-1, RGD.
Abstract: Overexpressed cell-surface receptors are hallmarks of many disease states and are often
used as markers for targeting diseased cells over healthy counterparts. Cell adhesion peptides, which
are often derived from interacting regions of these receptor-ligand proteins, mimic surfaces of intact
proteins and, thus, have been studied as targeting agents for various payloads to certain cell targets for
cancers and autoimmune diseases. Because many cytotoxic agents in the free form are often harmful
to healthy cells, the use of cell adhesion peptides in targeting their delivery to diseased cells has been
studied to potentially reduce required effective doses and associated harmful side-effects. In this review,
multiple cell adhesion peptides from extracellular matrix and ICAM proteins were used to selectively
direct drug payloads, signal-inhibitor peptides, and diagnostic molecules, to diseased cells
over normal counterparts. RGD constructs have been used to improve the selectivity and efficacy of
diagnostic and drug-peptide conjugates against cancer cells. From this precedent, novel conjugates of
antigenic and cell adhesion peptides, called Bifunctional Peptide Inhibitors (BPIs), have been designed
to selectively regulate immune cells and suppress harmful inflammatory responses in autoimmune
diseases. Similar peptide conjugations with imaging agents have delivered promising diagnostic
methods in animal models of rheumatoid arthritis. BPIs have also been shown to generate immune
tolerance and suppress autoimmune diseases in animal models of type-1 diabetes, rheumatoid arthritis,
and multiple sclerosis. Collectively, these studies show the potential of cell adhesion peptides in
improving the delivery of drugs and diagnostic agents to diseased cells in clinical settings.
