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

Cancer Immunology, Immunotherapy : CII
Kimberly R JordanJill 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 s...Continue Reading

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Citations

Sep 1, 2012·Immunologic Research·Jonathan D Buhrman, Jill E Slansky
Oct 10, 2013·The Journal of Biological Chemistry·Jonathan D BuhrmanJill E Slansky
Jun 5, 2013·Oncoimmunology·Jonathan D Buhrman, Jill E Slansky
Jan 25, 2014·Cancer Immunology Research·Stephanie K DouganHidde L Ploegh
Aug 30, 2017·Cancer Immunology Research·Tullia C BrunoJill E Slansky
Nov 29, 2017·Cancer Immunology Research·Nils-Petter RudqvistSandra Demaria
Jun 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Pengcheng WeiLei Yin

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Methods Mentioned

BETA
flow cytometry
FACS
PCR
454 Sequencing

Software Mentioned

Prism
Graphpad

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