Abstract SY41-02: Experimental methods for high throughput discovery and validation of tumor antigens

Abstract The discovery and validation of tumor associated T-cell antigens, which can include neoantigens, viral antigens, cancer testis antigens, and others, is fundamental to the design of both cancer vaccines and engineered cell cancer immunotherapies. However, identifying tumor specific antigens that are highly presented within tumors, and identifying and validating T cell receptors (TCRs) that are specific to those antigens, remains a non-trivial exercise. Even identifying and validating a single antigen-specific T cell clonotype for advancement into a clinic trial remains a daunting task. In this talk, I will discuss a number of new experimental and computational tools that are designed to accelerate this process. The experimental toolsets include reagents and strategies that allow for the capture and analysis of T cells specific to hundreds to thousands of tumor-associated Class I and Class II antigens simultaneously, with as many as 100 patient bloods analyzed in a single experiment. Single cell analysis of the resulting data yields a deep characterization of the captured T cells, including T cell receptor α/β genes, antigen-MHC specificity, T cell phenotype, and donor identification. This type of analysis, in turn, provides large data bases that can fuel new computational strategies that can be harnessed (at a still early stage) to predict which TCRα/β genes associate with which putative antigen-MHCs, or to extract the biochemical and biophysical characteristics of TCR-antigen pairings that influence T cell phenotype. Thus, this presentation will span both new experimental and new computational toolsets. Citation Format: James R. Heath. Experimental methods for high throughput discovery and validation of tumor antigens abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr SY41-02.