Anti-CD96 Neutralizing Antibody

CD96, also known as Tactile (T cell activation, increased late expression), is an immune checkpoint receptor of the immunoglobulin superfamily of proteins found in T and NK cells. Other proteins of the same superfamily include CD226 (also known as DNAM-1) and TIGIT (T cell immunoglobulin and ITM domain), with CD96 and TIGIT acting as inhibitory receptors and CD226 as a co-stimulatory receptor. CD96 binds to CD155, competing with CD226. CD96 plays a role in NK-cell adhesion to target cells, inhibiting NK cell cytokine release. It also plays an inhibitory role in Th9 cells and is a cancer stem cell marker. An imbalance in CD155/CD96 and CD155/CD226 can lead to lack of or to excessive immune responses. In LUAD (lung adenocarcinoma) the levels of CD96 in CD8+T cells are elevated compared to healthy individuals, possibly promoting a hypo-immune response. CD96, together with TIGIT, has become a widely researched target in immunotherapy, and blockage of CD96 binding to CD155 combined with other therapies, such as anti-PD-1 (programmed death protein 1) or doxorubicin chemotherapy, has shown great promise. The development of strategies to block CD96 inhibitory immune responses will continue to be an active area de research, opening new avenues of treatment for cancer patients.