T cell receptor (TCR) gene therapy to treat melanoma: Lessons from clinical and preclinical studies
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.
|Keywords||Chimeric antigen receptor, Gene therapy, Melanoma, T cell receptor|
|Persistent URL||dx.doi.org/10.1517/14712591003614756, hdl.handle.net/1765/28455|
Coccoris, M., Straetemans, G.C.M., Govers, C.C.F.M., Lamers, C.H.J., Sleijfer, S., & Debets, J.E.M.A.. (2010). T cell receptor (TCR) gene therapy to treat melanoma: Lessons from clinical and preclinical studies. Expert Opinion on Biological Therapy, 10(4), 547–562. doi:10.1517/14712591003614756