Engineered T cells for anti-cancer therapy

Curr Opin Immunol. 2012 Oct;24(5):633-9. doi: 10.1016/j.coi.2012.06.004. Epub 2012 Jul 18.

Abstract

Recent advances enabling efficient delivery of transgenes to human T cells have created opportunities to address obstacles that previously hindered the application of T cell therapy to cancer. Modification of T cells with transgenes encoding TCRs or chimeric antigen receptors allows tumor specificity to be conferred on functionally distinct T cell subsets, and incorporation of costimulatory molecules or cytokines can enable engineered T cells to bypass local and systemic tolerance mechanisms. Clinical studies of genetically modified T cell therapy for cancer have shown notable success; however, these trials demonstrate that tumor therapy with engineered high avidity tumor-reactive T cells may be accompanied by significant on-target toxicity, necessitating careful selection of target antigens and development of strategies to eliminate transferred cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Engineering / methods*
  • Genetic Engineering / trends
  • HLA Antigens / biosynthesis
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation*
  • Transduction, Genetic

Substances

  • HLA Antigens
  • Receptors, Antigen, T-Cell