Abstract 6786: NT-I7 as an adjuvant to DNA neoantigen vaccination enhances and prolongs neoantigen-specific anti-tumor immunity

Abstract

Abstract Background: IL-7 is an essential cytokine in the development and maintenance of antigen-specific T cells. NT-I7 (efineptakin alfa; NeoImmuneTech, Inc, Rockville, MD), is a long acting IL-7 composed of recombinant human IL-7 (rhIL-7) fused to a hybrid Fc antibody platform that has significantly improved in vivo stability and half-life compared to rhIL-7. DNA cancer neoantigen vaccines are a promising personalized cancer immunotherapy capable of generating strong anti-tumor immunity, but limited by a short-lived neoantigen-specific T cell response. We hypothesize NT-I7 as an adjuvant to a DNA neoantigen vaccine will enhance the magnitude and duration of neoantigen-specific anti-tumor immunity. Methods: C57BL/6 mice were vaccinated with DNA vaccine encoding neoantigens present in E0771 murine breast cancer model on days 0, 3, and 6. NT-I7 (5 mg/kg) was administered intravenously on day 4 or 13 during T cell expansion or contraction phase respectively. Primary T cell responses to neoantigens were assessed by IFN-γ ELISPOT. Tumor protection was evaluated by inoculating mice with 5×105 E0771 cells subcutaneously after receiving DNA vaccine with or without NT-I7. Duration of neoantigen-specific CD8 T cell immunity was determined by in vivo CFSE killing assay. Results: NT-I7 administered during the T cell contraction phase following the DNA vaccine increases the magnitude of neoantigen-specific T cell responses on day 20 compared to DNA vaccine alone. DNA vaccination and NT-I7 alone prior to tumor inoculation confers partial protection against tumor growth compared to control while DNA + NT-I7 during contraction phase rejects 100% of tumors. Compared to DNA vaccine alone, DNA vaccine + NT-I7 during contraction phase induces greater neoantigen-specific killing on day 41 (34.6% vs. 11.97%, p=0.03). Conclusion: NT-I7 as an adjuvant to a DNA neoantigen vaccine increases the magnitude and duration of neoantigen-specific anti-tumor immunity in a murine model. Clinical application of NT-I7 may help overcome immunologic shortcomings of current neoantigen vaccines. Citation Format: Michael Y. Chen, Ina Chen, Suangson Supabphol, Alexandra A. Wolfarth, Sara F. Martinez, Byung Ha Lee, Lijin Li, Xiuli Zhang, Peter S. Goedgebuure, William E. Gillanders. NT-I7 as an adjuvant to DNA neoantigen vaccination enhances and prolongs neoantigen-specific anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6786.