16-02-2017 | Image
Native T cells can recognize tumour-specific antigens in an MHC-dependent manner. The T cells also require co-stimulation for activation. Upon antigen recognition, without co-stimulatory signal, or with the stimulation of inhibitory molecules, such as through the PD-1–PD-L1 axis, the T cells can be induced to anergy or become exhausted. Immune-checkpoint inhibitors can block the inhibitory signal of T cells to avert T cells from anergy. BiTE® antibodies bring T cells and malignant cells into close proximity through dual antigen binding, and can induce T-cell activation without co-stimulatory signals. T-cells can also be engineered to express CARs to recognize cell-surface molecules independent of MHC. Later-generation CARs have both TCR and co-stimulatory signalling components, thereby activating the T cells without additional co-stimulatory signal. Abbreviations: ADC, antibody–drug conjugate; BiTE®, bispecific T-cell engager antibody; CAR, chimeric antigen receptor; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; mAb, monoclonal antibody; MHC, major histocompatibility complex; PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; TCR, T-cell receptor.