Immunodominance hierarchy of endogenous BBN963 bladder cancer antigens remain stable under anti-PD1 and anti-CTLA4 immunotherapy 3737

Abstract Description Personalized neoantigen vaccines for cancer have been used in clinical trials to induce de novo T cell responses and broaden the endogenous repertoire of tumor specific T cells. While computational approaches can predict MHC-restricted neoantigens, the breadth of T cell responses across a full neoantigen landscape has not been evaluated. This is due to limitations of computational methods to predict a comprehensive set of neoantigens and experimental methods to assess hundreds of neoantigens in parallel. The set of antigens a T cell population responds to ordered by the relative magnitude of response to each antigen is known as the immunodominance hierarchy. We developed a high throughput matrixed ELISpot design utilizing an in house matrixing and deconvoluting program, ACE, to evaluate CD8+ T cell responses against 140 predicted neoantigens in the BBN963 murine model of bladder cancer. We found the immunodominance hierarchy remained stable from animal to animal and under anti-PD1 and anti-CTLA treatment conditions, with anti-PD1 and anti-CTLA4 both boosting responses to antigens that already elicited responses in untreated groups. Our results highlight the need to further evaluate antigen-specific T cell responses in the context of cancer immunotherapy clinical trials. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)