Cancer Immunology, Immunotherapy

, Volume 62, Issue 2, pp 359–369

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
Original article

DOI: 10.1007/s00262-012-1336-z

Cite this article as:
Soto, C.M., Stone, J.D., Chervin, A.S. et al. Cancer Immunol Immunother (2013) 62: 359. doi:10.1007/s00262-012-1336-z

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 Kd value) against a class I tumor antigen mediated more effective tumor treatment than the wild-type affinity TCR (micromolar Kd 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.

Keywords

TCR Adoptive T-cell therapy Tumor targeting Cancer immunotherapy Melanoma 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Carolina M. Soto
    • 1
  • Jennifer D. Stone
    • 2
  • Adam S. Chervin
    • 2
  • Boris Engels
    • 3
  • Hans Schreiber
    • 3
  • Edward J. Roy
    • 1
  • David M. Kranz
    • 2
  1. 1.Neuroscience ProgramUniversity of IllinoisUrbanaUSA
  2. 2.Department of BiochemistryUniversity of IllinoisUrbanaUSA
  3. 3.Department of Pathology and Committee on ImmunologyThe University of ChicagoChicagoUSA

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