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successfully with corticosteroids. Commonly reported immune mediated adverse reactions include rash, itching and gastrointestinal disorders.

The CTLA-4 and PD-1/PD-L1 pathways have a similar negative effect on T-cell activity however the timing, signaling mechanism and location of immune inhibition by these two checkpoints differs. CTLA-4 is confined to T-cells whereas PD-1 is expressed on activated T cells, B cells and myeloid cells. While CTLA-4 functions during the priming phase of T-cell activation in lymph nodes, PD-1 functions during the effector phase largely in peripheral tissue. Recent studies show an enhanced antitumor response using a dual blockade compared with single agent blockade. This indicates that a blockade of both the CTLA-4 and PD-1/PD-L1 pathway could restore the immune responses of previously activated T-cells and reduce regulatory T-cell-mediated immunosuppression.

CAR-T-cell therapy does not use immune checkpoints as an alternative cancer treatment, but rather redesigns and redirects a patient’s own T-cells to specifically target and destroy tumor cells. Tumors use a variety of mechanisms to neutralize immune attacks. They can downregulate MHC molecule expression or disrupt antigen processing and presentation machineries. Chimeric antigen receptor (CAR) T-cell therapy use genetically engineered T-cells to find and destroy tumor cells in the body.

CAR-T cells are engineered to express synthetic receptors that redirect T-cells