Solid tumours: Building bridges to CAR-T success

Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has achieved remarkable impact in the treatment of selected blood cancers. However, meaningful clinical efficacy against nonhaematological malignancies has largely proven elusive. In this minireview, the main challenges to successful CAR-based intervention against solid tumours are considered. Obstacles are considered in four categories, namely target selection, trafficking of CAR-engineered cells to tumour deposits, the need to overcome the physical, chemical and biological hurdles to immune effector function that operate within the tumour microenvironment and selection of the best host cells for CAR engineering. A range of pre-clinical technologies that have been developed in an effort to overcome these issues are also surveyed. Although clinical progress comes dropping slow, rapid and continued advances in cellular engineering and manufacture, coupled with the emergence of several complementary interventions bodes well for the future success of CAR T-cell immunotherapy of solid tumours. In contrast to blood cancers, solid tumours have largely proven refractory to CAR-based immunotherapy. Obstacles include the lack of tumour-specific targets, difficulty in entry and infiltration of tumour deposits and the myriad of immunosuppressive factors that operate within the tumour microenvironment. We also consider various host cell types for CAR engineering that have been proposed as alternatives to conventional T-cells. image