Long-Acting Recombinant IL-7 (rhIL-7-hyFc) Enhances the Primary and Memory Neoantigen-Specific Immune Response to Breast Cancer Personalized Cancer Vaccines

Background: Personalized cancer vaccines (PCVs) are a promising form of cancer immunotherapy, capable of eliciting robust neoantigen-specific immune responses. However, cancer neoantigens are variable in terms of immunogenicity, and PCVs may be less effective when targeting weak neoantigens. Strong and durable immune responses are also likely to be critical for vaccine efficacy. Interleukin-7 (IL-7) is a common gamma-chain cytokine known to support T cell development and survival, and a long-acting form of recombinant human IL-7 fused with hybrid Fc (rhIL-7-hyFc) has shown potential to enhance immune responses in early-stage clinical trials. Methods: In this study, we evaluated the ability of rhIL-7-hyFc to serve as a molecular adjuvant to a DNA PCV in the E0771 murine breast cancer model. Results: We found that the combination of rhIL-7-hyFc and DNA PCV treatment prolonged neoantigen-specific CD8+ T cell responses, improved functional memory as measured based on in vivo cytotoxicity, and increased the number of neoantigen-specific tumor-infiltrating lymphocytes (TILs), resulting in improved prophylactic tumor protection and durable memory responses. Conclusions: Our findings support the potential of rhIL-7-hyFc to enhance the efficacy of PCVs and suggest clinical utility for adjuvant rhIL-7-hyFc in cancer immunotherapy.