Two recent studies titled “IGF-1R Peptide Vaccines/Mimics Inhibit the Growth of BxPC3 and JIMT-1 Cancer Cells in vitro and in vivo and Combined Therapy with HER-1 and HER-2 Peptides Induces Effective Anti-tumor Effects” and “HER-3 Peptide Vaccines/Mimics and Combined therapy with IGF-1R, HER-2, and HER-1 Peptides Induces Effective Anti-tumor Effects in vitro and in vivo and Inhibit Breast and Pancreatic Cancer Cells“, published in the September issue of OncoImmunology journal, report the successful development of two new peptide vaccines and inhibitors with anti-tumor activity.
In this study, the team of researchers from the Ohio State University Comprehensive Cancer Center evaluated the efficacy of treatment with HER-3 and IGF-1R inhibitors alone and administered together with HER-1 and HER-2 vaccines, thus targeting different cell receptors with combined peptide agents, increasing their efficiency and preventing drug resistance.
IGF-1R (insulin-like growth factor receptor 1R) and HER-3 (human epidermal growth factor receptor 3) are two receptors commonly overexpressed in cancer cells – IGF-1R in colon, breast and pancreatic cancers, and HER-3 in EGFR and HER-2 overexpressing cancers.
The team used colon cancer cell lines, along with breast and pancreatic, and two animal models (triple-negative breast cancer and pancreatic cancer) for their studies.
Pravin Kaumaya, PhD, director of the division of vaccine development at the Ohio State University Comprehensive Cancer Center, noted in a Science Direct article “Combining these novel immunotherapy peptides could significantly improve response rates and rates of durable remissions for the multiple types of cancer that depend on EGFR, HER-2, HER-3 or IGF-1R signaling.”
The authors found combining both HER-3 and IGF-1R inhibitors significantly reduced cancer cell proliferation by ate least 60%, when compared to treatment alone (40% HER-3, 30% IGF-1R); significant anti-tumor effects were also observed in other combinations – HER-2/HER-3 and HER-3/ IGF-1R for breast cancer and notably for breast cancer resistant-cell lines (such as trastuzumab-resistant).
“We believe that blocking HER-3 might provide a route for overcoming resistance to agents that target EGFR or HER-2,” Dr. Kaumaya added.
The anti-tumor activity was observed in other cancer models, with breast, pancreatic and colon cancers showing anti=tumor activities upon co-treatment with HER-3/IGF-1R and HER-1/IGF-1R in triple-negative breast cancer and pancreatic cancer. Additionally, both HER-3 and IGF-1R triggered high levels of antibody production in rabbits.
Dr. Kaumaya commented, “These two studies independently identify important HER-3 and IGF-1R vaccine epitopes that elicited significant anti-tumor responses in a variety of human cancer-cell lines and in animal models. They also provide additional evidence that combining these agents has synergistic antitumor effects in various cancer types that express HER receptors.”
These results here described highlight how combined immunotherapy is a promising therapeutical approach to treat different types of cancer and overcome resistance to cancer treatments that rely on single agents.