Anti-CTLA-4 Immunotherapy

Cluster of Differentiation (CD) markers play an important role in the differentiation of B cells, T cells and NK (natural killer) cells. These markers are often responsible for the identification of certain cancers and tumors, resulting in CD markers being good candidates for cancer therapies.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)(CD152) is a protein receptor found on T cells. Both CTLA-4 and CD28 bind to B7-1/2 on antigen-presenting cells (APCs) such as dendritic cells and B cells. CTLA-4 has been shown to bind B7-1/2 with a higher affinity than CD28 does. This means that CTLA-4 'hijacks' B7 proteins away from T cell co-stimulatory CD28 receptors, resulting in T cells remaining in a resting state.

CTLA-4 functions as an immune checkpoint and it downregulates the immune response through repression of T cell proliferation and cytokine production. Mice deficient in CTLA-4 develop spontaneous lymphoproliferative disease with multiorgan infiltration within 3–4 weeks of birth, which suggests an aberrant regulation of T cell activation or proliferation.

Cancer can arise when proteins produced by tumour cells express antigens that are not normally seen by the immune system, resulting in an immune response. Cancer cells commonly use CTLA-4 to escape the adaptive immune response and it is found on roughly one third of metastatic cancer cells.

Anti-CTLA-4 monoclonal antibodies such as Yervoy® (Ipilimumab) are used for treating cancer by blocking the inhibitory effects of CTLA-4 on T cells. Ipilimumab can be used for the treatment of melanoma on it's own or else it can be used in combination with Opdivo® (nivolumab).

By activating T cells to recognize tumor cell antigens, anti-CTLA-4 therapy has shown great therapeutic potential in the treatment of melanoma, non-small cell lung cancer, prostate cancer, renal cancer, gastroesophageal carcinoma, pancreatic cancer and many others.