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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)359-369
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume62
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

T-Cell Antigen Receptor
T-Lymphocytes
Neoplasms
Histocompatibility Antigens Class I
Helper-Inducer T-Lymphocytes
Adoptive Transfer
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Immunotherapy
Melanoma
Cytokines

Keywords

  • Adoptive T-cell therapy
  • Cancer immunotherapy
  • Melanoma
  • TCR
  • Tumor targeting

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

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

In: Cancer Immunology, Immunotherapy, Vol. 62, No. 2, 01.02.2013, p. 359-369.

Research output: Contribution to journalArticle

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