Novel CTLA-4 Antibodies of Potent Antitumor Activity Were Verified in Humanized Mouse Models
CTLA-4 is a member of the immunoglobulin superfamily, and is homologous to the co-stimulatory protein CD28, and both receptors bind to the same ligands, CD80(B7-1) and CD86(B7-2). Importantly, cancer cells can be recognized and destroyed by the host’s immune system. In this setting, CTLA-4 functions as a brake to dampen anti-tumor T cell responses, which promote cancer progression.
We have interests in searching for an antibody that may work as good as or exceed the approved CTLA-4 antibody. Antibodies blocking CTLA-4 are expected to subvert T cell inhibition. Moreover, regulatory T cells residing in the tumor microenvironment are sensitive to anti-CTLA-4 antibody since they have higher expression levels of CTLA-4 comparing to the activated T cells. Yervoy, the first FDA-approved CTLA-4 antibody, protects a fraction of cancer patients when either used alone or in combination with other drugs. Here, we reported that we generated two humanized antibodies whose efficacy is equivalent or exceed that of Yervoy using the pharmacological efficacy evaluation platform established at Biocytogen. Potent inhibition and biological activity were further demonstrated by a series of tests in vitro. In conclusion, we successfully discovered two humanized antibodies that exhibit appealing anti-cancer activity in vivo. The clinical evaluation of these new entities are wanted.
