Relapse or eradication of cancer is predicted by peptide-MHC affinity

Cancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro . We found that tumor eradication by T cells required high affinities of the targeted peptides for MHC class I. Affinities of at least 10 nM were required for relapse-free...

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Bibliographic Details
Published in:Cancer cell 2013-04, Vol.23 (4), p.516-526
Main Authors: Engels, Boris, Engelhard, Victor H., Sidney, John, Sette, Alessandro, Binder, David C., Liu, Rebecca B., Kranz, David M., Meredith, Stephen C., Rowley, Donald A., Schreiber, Hans
Format: Article
Language:English
Online Access:Get full text
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Summary:Cancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro . We found that tumor eradication by T cells required high affinities of the targeted peptides for MHC class I. Affinities of at least 10 nM were required for relapse-free regression. Only high-affinity peptide-MHC interactions led to efficient cross-presentation of antigen, thereby stimulating cognate T cells to secrete cytokines. These findings highlight the importance of targeting peptides with high affinity for MHC class I when designing T cell-based immunotherapy.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2013.03.018