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

TL;DR

A long-acting form of IL-7 improves the effectiveness of personalized cancer vaccines in a mouse model of breast cancer by boosting immune responses.

Contribution

Demonstrates that rhIL-7-hyFc enhances neoantigen-specific immune memory and tumor protection when combined with DNA-based personalized cancer vaccines.

Findings

Combining rhIL-7-hyFc with DNA PCV prolonged CD8+ T cell responses and improved immune memory.

The treatment increased tumor-infiltrating lymphocytes and provided better tumor protection.

rhIL-7-hyFc shows potential as an adjuvant for personalized cancer vaccines in immunotherapy.

Abstract

Personalized cancer vaccines (PCVs) can train the immune system to attack tumors by targeting neoantigens, but their effectiveness depends on the strength and durability of the immune response. In this study, we tested whether a long-acting form of interleukin-7 (rhIL-7-hyFc), a molecule known to support T cell survival, could improve the performance of a DNA-based PCV in a mouse breast cancer model. We found that combining rhIL-7-hyFc with the vaccine led to stronger and longer-lasting CD8+ T cell responses, better immune memory, and more tumor-infiltrating lymphocytes. This combination also helped prevent tumor growth more effectively. Our results suggest that rhIL-7-hyFc could be a useful addition to PCV-based cancer treatments.

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.

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