CAR-T Cells and Recent Advances in Clinical Cellular Immunotherapy
Gu Y., Rampotas A., Sweeney C., Roberts DJ., Chakraverty R.
Cellular immunotherapy is now the focus of huge attention and investment from the biopharmaceutical industry, with many early-phase trials demonstrating impressive clinical responses. Spatial-omics demonstrate some causes of poor immunotherapy response, such as infiltration of only exhausted T cells into the tumour niche during checkpoint blockade therapy, or endogenous cytotoxic T cells and/or chimeric antigen receptor (CAR)-T cells remaining excluded from the tumour by physical barriers, such as trapping by stroma. Tumour antigens can be therapeutically targeted by vaccination or by adoptive transfer of antigen-specific T cells. A more pharmacological ‘off-the-shelf’ approach to engage native T cells against malignant cells is by using bispecific T-cell engagers and bispecific antibodies. Early trials of natural killer (NK)-cell immunotherapy were based upon infusion of autologous NK cell-activating cytokines or ex vivo activated NK cells, but were largely disappointing.