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

Miriam Coccoris, T Straetemans, Coen Govers, Cor Lamers, Stefan Sleijfer, Reno Debets

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Scopus)

Abstract

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 antitumour 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.
Original languageUndefined/Unknown
Pages (from-to)547-562
Number of pages16
JournalExpert Opinion on Biological Therapy
Volume10
Issue number4
DOIs
Publication statusPublished - 2010

Research programs

  • EMC MM-03-86-01
  • EMC MM-03-86-08

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