Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor

Sci Rep. 2014 Jan 6;4:3571. doi: 10.1038/srep03571.

Abstract

Genetically modified T cells to recognize tumor-associated antigens by transgenic TCRs or chimeric antigen receptors (CAR) have been successfully applied in clinical trials. However, the disadvantages of either TCR mismatching or the requirement of a surface tumor antigen limit their wider applications in adoptive T cell therapy. A TCR-like chimeric receptor, specific for the melanoma-related gp100/HLA-A2 complex was created by joining a TCR-like antibody GPA7 with the endodomains of CD28 and CD3-ζ chain. This TCR-like CAR, GPA7-28z, was subsequently introduced into human T cells. Retargeted T cells expressing GPA7-28z could exhibit efficient cytotoxic activities against human melanoma cells in vitro in the context with HLA-A2. Furthermore, infusion of GPA7-28z-transduced T cells suppressed melanoma progression in a xenograft mouse model. Redirecting human T cells with TCR-like CARs would be a promising alternative approach to TCR-mediated therapy for melanoma patients, which is also feasible for targeting a variety of other tumor antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Humans
  • Melanoma / immunology*
  • Melanoma / pathology
  • Mice
  • Mice, SCID
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured

Substances

  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins