The binding of Programmed Cell Death Protein 1 (PD-1), a receptor expressed on activated T cells, to its ligands, PD-L1 and PD-L2, negatively regulates immune responses. The PD-1 ligands are found on most cancers, and PD-1:PD-L1/2 interaction inhibits T cell activity and allows cancer cells to escape immune surveillance. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for a number of cancers, as well as multiple sclerosis, arthritis, lupus, and type I diabetes.

CTLA4 is a member of the immunoglobulin superfamily. It is expressed by activated T cells and transmits an inhibitory signal to T cells. CTLA4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells. CTLA-4 binds CD80 and CD86 with greater affinity and avidity than CD28 thus enabling it to outcompete CD28 for its ligands and act as an “off” switch when bound to CD80 or CD86. Not surprisingly, CTLA-4 is an important drug target for the regulation of the host’s response to cancer.

Figure 1. Dose Response of Blocking Antibodies in PD-1/CTLA4 Dual Effector Reporter Cells (C16) With PD-L1/CD80&CD86 aAPC Cells.