n IgG1 mAB used for the treatment of melanoma. It is currently undergoing clinical trials for the treatment of non-small cell lung carcinoma, small cell lung cancer, bladder cancer and metastatic prostate cancer. Like all immune checkpoint inhibitors, CTLA-4 inhibitors are associated with immune mediated toxicities, most of which can be managed 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 to surface antigens for tumor elimination. A CAR is a fusion protein composed of 3 domains. These include an extracellular single chain variable fragment that serves as the target binding domain, a transmembrane spacer domain and an intracellular signaling domain with cytoplasmic proteins that provide T-cell activation signals. These domains allow CAR-T cells to recognize cell surface tumor antigens leading to antigen-specific T-cell activation, proliferation, and cytokine production. Many CARs are also designed with elements that enhance T-cell persistence and activity. After a CAR is designed, it is introduced into T-cells. Initially, through leukapheresis, peripheral blood mononuclear cells from a patient are collected and the blood is separated into different components. Once>