Genetically modified T cells in cancer therapy: opportunities and challenges

Abstract

Tumours use many strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated in particular by the successful use of genetically modified T cells to treat B cell haematological malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cell immunotherapy to many patients with different tumour types remain. These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies.

IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts

“…Previous clinical studies effort to reactivate exhausted T cells as treatment for chronic infections or tumor disease [35]. However, the mechanisms leading to T cell exhaustion are unknown.…”

New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know

“…Other incoming techniques involving genetically modified T cells to recognize antigens associated with tumours by chimeric antigen receptors (CAR) or transgenic high-affinity T-cell receptors (TCRs) have been recently applied in clinical trials in melanoma and few other cancer types [155][156][157]. Emerging immunotherapies in melanoma flagged here, even though thrilling and promising, require separate review papers, unfortunately remaining far beyond the scope of this work.…”

Cytotoxic T cells and Cancer Therapy

“…+ and CD8 + T cells is developed by associating a defined TCR (tumorassociated) that is specific for a new MHC-peptide complex and has been tested with success in several in vitro studies (Maher, 2012;Sharpe & Mount, 2015). Permission has been granted to a greater repertoire of attractive protein antigens compared to CAR and evidences suggest that in comparison to ectopic TCR the immunogenicity of CAR derived from rodent hybridoma based scFv is found to be greater.…”