Next generation cellular therapies for cancer

Therapies that enhance the immune response to tumours have revolutionised the management of cancer. However, most tumours do not have a high mutational burden and are therefore not ‘visible’ to the immune system or evolve alternate immunosuppressive mechanisms to escape immune-surveillance. As a consequence, such tumours remain largely unresponsive to current class-leading immunotherapies, including those targeting immune checkpoints. Chimeric antigen receptor (CAR) T cell therapy has emerged as an exciting immunotherapy approach for ‘non-immunogenic’ cancers, as it does not rely on endogenous anti-tumour immunity. CAR T cells are autologous T cells engineered to express a CAR specific for a tumour antigen. CAR T cells targeting CD19 have transformed the treatment of acute lymphoblastic leukaemia, with clinical response rates of up to 90%. However, there are several limitations that prohibit the widespread use of CAR T cells. In particular, CAR T cell generation is cumbersome, costly, the side effects can be life threatening and most importantly, their effectiveness in solid tumours is yet to be realised Some of these limitations can be overcome using CAR Natural Killer (NK) cells. NK cells elicit rapid anti-tumour responses and offer an alternative to T cells in adoptive cell therapy. Projects focussed on the development of next generation CAR T and CAR NK cell therapies for solid tumours are available.