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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 2/2013

01-02-2013 | Original article

MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR

Authors: Carolina M. Soto, Jennifer D. Stone, Adam S. Chervin, Boris Engels, Hans Schreiber, Edward J. Roy, David M. Kranz

Published in: Cancer Immunology, Immunotherapy | Issue 2/2013

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Abstract

Clinical studies with immunotherapies for cancer, including adoptive cell transfers of T cells, have shown promising results. It is now widely believed that recruitment of CD4+ helper T cells to the tumor would be favorable, as CD4+ cells play a pivotal role in cytokine secretion as well as promoting the survival, proliferation, and effector functions of tumor-specific CD8+ cytotoxic T lymphocytes. Genetically engineered high-affinity T-cell receptors (TCRs) can be introduced into CD4+ helper T cells to redirect them to recognize MHC-class I-restricted antigens, but it is not clear what affinity of the TCR will be optimal in this approach. Here, we show that CD4+ T cells expressing a high-affinity TCR (nanomolar K d value) against a class I tumor antigen mediated more effective tumor treatment than the wild-type affinity TCR (micromolar K d value). High-affinity TCRs in CD4+ cells resulted in enhanced survival and long-term persistence of effector memory T cells in a melanoma tumor model. The results suggest that TCRs with nanomolar affinity could be advantageous for tumor targeting when expressed in CD4+ T cells.
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Metadata
Title
MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR
Authors
Carolina M. Soto
Jennifer D. Stone
Adam S. Chervin
Boris Engels
Hans Schreiber
Edward J. Roy
David M. Kranz
Publication date
01-02-2013
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 2/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-012-1336-z

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