TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines

Abstract

A major goal of immunotherapy for cancer is the activation of T cell responses against tumor-associated antigens (TAAs). One important strategy for improving antitumor immunity is vaccination with peptide variants of TAAs. Understanding the mechanisms underlying the expansion of T cells that respond to the native tumor antigen is an important step in developing effective peptide-variant vaccines. Using an immunogenic mouse colon cancer model, we compare the binding properties and the TCR genes expressed by T cells elicited by peptide variants that elicit variable antitumor immunity directly ex vivo. The steady-state affinity of the natural tumor antigen for the T cells responding to effective peptide vaccines was higher relative to ineffective peptides, consistent with their improved function. Ex vivo analysis showed that T cells responding to the effective peptides expressed a CDR3β motif, which was also shared by T cells responding to the natural antigen and not those responding to the less effective peptide vaccines. Importantly, these data demonstrate that peptide vaccines can expand T cells that naturally respond to tumor antigens, resulting in more effective antitumor immunity. Future immunotherapies may require similar stringent analysis of the responding T cells to select optimal peptides as vaccine candidates.

DOI: 10.1007/s00262-012-1217-5

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@inproceedings{Jordan2012TCRHR, title={TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines}, author={Kimberly R Jordan and Jonathan D. Buhrman and Jonathan Sprague and Brandon L. Moore and Dexiang Gao and John W. Kappler and Jill E. Slansky}, booktitle={Cancer Immunology, Immunotherapy}, year={2012} }