SUMMARY
Chimeric antigen receptor (CAR) T-cell therapy is a new cancer immunotherapy targeting specific cell surface antigens. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukaemia (ALL) and is currently being studied in other cancer types, including multiple myeloma and chronic lymphocytic leukaemia. With the unprecedented success of CAR T cells in haematological malignancies, a growing number of (pre)clinical studies are focusing on translating this treatment to solid tumours. However, response rates to CAR T-cell therapy have so far been much less favourable in non-haematologic malignancies, mainly due to a paucity of unique tumour target antigens, limited CAR T-cell trafficking to tumour sites, tumour heterogeneity, antigen loss, the presence of an immune suppressive tumour microenvironment and recognition of normal cells expressing the targeted antigen. A broad range of strategies is currently being explored to overcome these hurdles. For example, TCR-CAR-T hybrids have been developed that can also target intracellular antigens which broadens the potential scope of the CAR-T cell strategy. This article reviews completed and ongoing CAR T-cell trials in solid tumours and discusses the strategies to improve the efficacy of this treatment modality in solid tumours, including accelerated production flows. CAR-T’s might very well be the upcoming major advance in cancer treatment.
