T cell receptor (TCR) gene therapy to treat melanoma: lessons from clinical and preclinical studies

Expert Opin Biol Ther. 2010 Apr;10(4):547-62. doi: 10.1517/14712591003614756.


Importance of the field: Adoptive T cell therapy (ACT) with tumour infiltrating lymphocytes is currently the best treatment option for metastatic melanoma. Despite its clinical successes, ACT has limitations in availability and generation of therapeutic T cells for a larger group of patients. Introduction of tumour-specific T cell receptors into T cells, termed TCR gene therapy, can provide an alternative for ACT that is more widely applicable and might be extended to other types of cancer.

Areas covered in this review: The current status of TCR gene therapy studies including clinical challenges, such as on-target toxicity, compromised anti-tumour T cell responses, compromised T cell persistence and potential immunogenicity of receptor transgenes. Strategies to address these challenges are covered.

What the reader will gain: A listing and discussion of strategies that aim at improving the efficacy and safety of TCR gene therapy. Such strategies address antigen choice, TCR mis-pairing, functional avidity and persistence of T cells, immune responses towards receptor transgenes, and combination of ACT with other therapies.

Take home message: To ensure further clinical development of TCR gene therapy, it is necessary to choose safe T cell target antigens, and implement (combinations of) strategies that enhance the correct pairing of TCR transgenes and the functional avidity and persistence of T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Receptors, Antigen, T-Cell / genetics*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • T-Lymphocytes / immunology
  • Transgenes


  • Receptors, Antigen, T-Cell