TT3 antigen (TT3)

TT3 is a novel, non-human (human-absent) antigen utilized as a synthetic therapeutic target in a combinatorial cancer treatment strategy developed by Betta Pharmaceuticals [40, 49]. This approach involves the use of a genetically modified oncolytic vaccinia virus, V-113, which is engineered to selectively infect tumor cells and induce the stable expression of the TT3 protein on their surface [48, 54]. Once expressed, the TT3 antigen serves as a specific "flag" for the immune system, allowing for precise targeting of the tumor [49, 50]. A companion therapeutic, BK-001, is a bispecific T-cell engager (BiTE) antibody designed to bind simultaneously to the TT3 antigen on the tumor cell and the CD3 receptor on T-cells [40, 47]. This dual binding brings T-cells into close proximity with the tumor cells, triggering T-cell activation and the subsequent destruction of the cancer cells through T-cell-dependent cellular cytotoxicity (TDCC) [48, 49]. By using a "human-absent" antigen like TT3, this technology aims to create a highly specific target that is not present in normal human tissues, thereby minimizing off-target toxicity and overcoming the challenges of identifying endogenous tumor-specific antigens [40, 54].

Other names

Human-absent antigen TT3Non-primate endogenous antigenic proteinTT3 proteinTT3 polypeptide

TT3 serves as a synthetic, human-absent target antigen that is selectively expressed on the surface of tumor cells via a genetically modified oncolytic virus (V-113). Once expressed, it is targeted by a bispecific T-cell engager (BiTE) antibody (BK-001) that simultaneously binds to TT3 and the CD3 receptor on T-cells, recruiting and activating T-cells to mediate T-cell-dependent cellular cytotoxicity (TDCC) against the tumor cells [40, 49].