Title |
TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines
|
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Published in |
Cancer Immunology, Immunotherapy, February 2012
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DOI | 10.1007/s00262-012-1217-5 |
Pubmed ID | |
Authors |
Kimberly R. Jordan, Jonathan D. Buhrman, Jonathan Sprague, Brandon L. Moore, Dexiang Gao, John W. Kappler, Jill E. Slansky |
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. |
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