Peptide vaccines and targeting HER and VEGF proteins may offer a potentially new paradigm in cancer immunotherapy.
The ErbB family (HER-1, HER-2, HER-3 and HER-4) of receptor tyrosine kinases has been the focus of cancer immunotherapeutic strategies while antiangiogenic therapies have focused on VEGF and its receptors VEGFR-1 and VEGFR-2. Agents targeting receptor tyrosine kinases in oncology include therapeutic antibodies to receptor tyrosine kinase ligands or the receptors themselves, and small-molecule inhibitors. Many of the US FDA-approved therapies targeting HER-2 and VEGF exhibit unacceptable toxicities, and show problems of efficacy, development of resistance and unacceptable safety profiles that continue to hamper their clinical progress. The combination of different peptide vaccines and peptidomimetics targeting specific molecular pathways that are dysregulated in tumors may potentiate anticancer immune responses, bypass immune tolerance and circumvent resistance mechanisms. The focus of this review is to discuss efforts in our laboratory spanning two decades of rationally developing peptide vaccines and therapeutics for breast cancer. This review highlights the prospective benefit of a new, untapped category of therapies biologically targeted to EGF receptor (HER-1), HER-2 and VEGF with potential peptide 'blockbusters' that could lay the foundation of a new paradigm in cancer immunotherapy by creating clinical breakthroughs for safe and efficacious cancer cures.
Departments of Obstetrics & Gynecology, OSU Wexner Medical Center, James Cancer Hospital & Solove Research Institute & the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. pravin.kaumaya@osumc.edu
Pravin T P
PT
Kaumaya
Kevin Chu
KC
Foy
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D018716:Molecular Mimicry / Q000276:immunology; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D022223:Vaccines, Subunit / Q000494:pharmacology / Q000627:therapeutic use*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology
D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D022223:Vaccines, Subunit; D042442:Vascular Endothelial Growth Factors