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Abstract 3571: Prevention of non-small cell lung cancer with kras mutation using a novel peptide vaccine


 Non-small cell lung cancer (NSCLC) is a significant health issue associated with morbidity and mortality. One of the important findings to emerge in NSCLC is that specific genetic mutations that lead to cancer development occur early in the disease process. Unfortunately, identifying NSCLC at its earliest stages when it is curable has been a challenge even in high risk individuals. These gene mutations, especially those involving the Kras protein, can “drive” the development of NSCLC cancer as they alter the regulation of cell growth or block programmed cell death. Mutations in Kras have been reported in 30% of lung cancer cases and are associated with worse outcomes. This neo-antigen cannot generate effective anti-tumor immunity, suggesting lack of a cellular, cytotoxic immune response to cancer cells on mucosal/epithelial surfaces. No effective therapies specifically targeting mutant Kras have been developed. To overcome poor immunogenicity of neo-antigen, newer adjuvants (NA), biocompatible nanoparticles, were used to enhance immune response. It has been reported NA can produce cytotoxic and mucosal immunity safely in humans. Producing this type of immune response to mutated Kras through immunization could produce a significant anti-tumor effect. In the current study, we first tested NA combined with mutated and wild type (MHC II) Kras peptides vaccine for immunogenicity on the same genetic background as the animals in the inducible tumor model. Our data have demonstrated that NA in combination with multiple Kras peptides can increase CD4+ and CD8+ T cell numbers in the draining lymph node cells and enhance antigen specific TH1 and TH17 responses by luminex and ELISpot to increase the ability of the vaccine to kill tumor cells and elicit long-lasting immune memory. Furthermore, we evaluated anti-tumor efficacy of this vaccine in tetracycline-inducible mouse model with Kras mutation. In this challenge model, vaccinated mice showed higher IFNɤ and IL-17 levels and decreased the tumor incidence significantly compared to PBS or peptides alone group. In conclusion, we have demonstrated the antigen-specific cellular immune responses and mononuclear cell infiltrates correlate with tumor prevention. Our data suggest that this novel vaccine could prevent the development of NSCLC after validation in an appropriate animal model.
 Citation Format: Suhe Wang, Zhengyi Cao, Jesse Chen, Janczak Katarzyna, James Baker. Prevention of non-small cell lung cancer with kras mutation using a novel peptide vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3571.