HER1 (EGFR) and/or HER2 Inclusion Potentiates the Antitumor Effect Elicited by a HER3-Specific Monovalent Vaccine

Abstract The development of active specific immunotherapies for cancer treatment has mainly focused on the design of CTL vaccines. However, the inactivation of signaling induced by membrane oncogenes highlights the value of vaccines that generate a polyclonal antibody response against these oncogenes. In this sense, the EGFR family oncogenes play a critical role in tumor biology and could, therefore, be targeted by antibodies generated through vaccination to block receptor-mediated signaling and induce an antitumor effect in cancer cells. In this study, we focus on demonstrating the antitumor properties triggered by the specific polyclonal response of vaccine candidates based on three members of the EGFR family (HER1, HER2, and HER3). We are presenting two novel HER3-based multivalent vaccine candidates: a bivalent candidate that combines the extracellular domains of HER3 and HER2 in its formulation and a trivalent candidate that includes the extracellular domains of HER3, HER2, and HER1. Both candidates are adjuvanted with a combination of VSSP and Montanide ISA 51. As part of our study, we compared the antitumor properties of both HER3-based multivalent candidates with the monovalent HER3-based vaccine candidate previously reported. Our results confirm that the polyclonal response generated by HER3-based vaccine candidates has in vitro and in vivo antitumor effects through the induction of apoptosis, especially in resistance scenarios, and indicate that these effects can be enhanced with the inclusion of HER1 and HER2 in the formulation. Our results suggest the potential use of HER3-based multivalent vaccines as a first-line treatment or after resistance to first-generation anti-HER1 tyrosine kinase inhibitor therapies appears.