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Preventing tumor escape by targeting a post-proteasomal trimming independent epitope

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Official URL:https://doi.org/10.1084/jem.20160636
PubMed:View item in PubMed
Creators Name:Textor, A. and Schmidt, K. and Kloetzel, P.M. and Weissbrich, B. and Perez, C. and Charo, J. and Anders, K. and Sidney, J. and Sette, A. and Schumacher, T.N.M. and Keller, C. and Busch, D.H. and Seifert, U. and Blankenstein, T.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Volume:213
Number:11
Page Range:2333-2348
Date:17 October 2016
Abstract:Adoptive T cell therapy (ATT) can achieve regression of large tumors in mice and humans; however, tumors frequently recur. High target peptide-major histocompatibility complex-I (pMHC) affinity and T cell receptor (TCR)-pMHC affinity are thought to be critical to preventing relapse. Here, we show that targeting two epitopes of the same antigen in the same cancer cells via monospecific T cells, which have similar pMHC and pMHC-TCR affinity, results in eradication of large, established tumors when targeting the apparently subdominant but not the dominant epitope. Only the escape but not the rejection epitope required postproteasomal trimming, which was regulated by IFN-gamma, allowing IFN-gamma-unresponsive cancer variants to evade. The data describe a novel immune escape mechanism and better define suitable target epitopes for ATT.
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Additional Information:Erratum in: J Exp Med 214(2): 567.
Item Type:Article

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