Adoptive T-cell therapy for cancer: The era of engineered T cells

Eur J Immunol. 2015 Sep;45(9):2457-69. doi: 10.1002/eji.201545552. Epub 2015 Aug 21.

Abstract

Tumors originate from a number of genetic events that deregulate homeostatic mechanisms controlling normal cell behavior. The immune system, devoted to patrol the organism against pathogenic events, can identify transformed cells, and in several cases cause their elimination. It is however clear that several mechanisms encompassing both central and peripheral tolerance limit antitumor immunity, often resulting into progressive diseases. Adoptive T-cell therapy with either allogeneic or autologous T cells can transfer therapeutic immunity. To date, genetic engineering of T cells appears to be a powerful tool for shaping tumor immunity. In this review, we discuss the most recent achievements in the areas of suicide gene therapy, and TCR-modified T cells and chimeric antigen receptor gene-modified T cells. We provide an overview of current strategies aimed at improving the safety and efficacy of these approaches, with an outlook on prospective developments.

Keywords: Adoptive T-cell therapy; Chimeric antigen receptor; Genetic engineering; Immunotherapy; T cells; T-cell receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Cell Engineering / methods*
  • Cell- and Tissue-Based Therapy / methods
  • Forecasting
  • Gene Expression
  • Genes, Transgenic, Suicide*
  • Genetic Therapy / methods
  • Humans
  • Immunotherapy, Adoptive / methods
  • Immunotherapy, Adoptive / trends*
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / immunology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*

Substances

  • Antigens, Neoplasm
  • Mutant Chimeric Proteins
  • Receptors, Antigen, T-Cell