Commentary on “A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors”

The field of adoptive immunotherapy has grown from the early days of a few academic groups administering cytotoxic lymphocytes (CTL) or tumor infiltrating lymphocytes (TIL), to the use of genetically engineered T cells being developed as drug products by multinational pharmaceutical companies. The first demonstration of the effective use of gene engineered T cells was reported in 2006 when T-cell receptor (TCR) engineered cells were shown to mediate cancer regression in 2 of 13 patients with malignant melanoma (1). In the subsequent years, several groups spearheaded the clinical developed an alternative antigen targeting technology based on chimeric antigen receptors (CAR), which mediate tumor antigen recognition via ligand binding domains (generally antibodies) and bypass the TCR complex by being fusion proteins with T cell signaling domains such as CD3zeta (2-4). CARs based on anti-CD19 mAbs have been shown to mediate durable cancer regression in leukemia and lymphoma in multiple clinical trials and it is these results that most stimulated the excitement of this therapy as a new treatment modality for cancer (5-7).