tumor-selective anti-CTLA-4 monoclonal antibody

Tumor-selective anti-CTLA-4 monoclonal antibodies represent a next-generation class of immune checkpoint inhibitors engineered to provide localized immune activation within the tumor microenvironment while minimizing systemic immune-related adverse events (irAEs). Conventional CTLA-4 inhibitors, such as ipilimumab, are often limited by significant systemic toxicities due to broad T-cell activation. Tumor-selective variants employ various engineering strategies to achieve this specificity: XTX101 (developed by Xilio Therapeutics) and ADG116 (Adagene) utilize "masking" technologies where the antibody remains inactive in systemic circulation and is selectively activated by proteases prevalent in the tumor milieu. Another candidate, gotistobart (ONC-392/BNT316, developed by OncoC4 and BioNTech), is designed to avoid interference with CTLA-4 recycling in peripheral tissues, thereby maintaining peripheral tolerance while effectively depleting intratumoral regulatory T cells. These agents are primarily being investigated for the treatment of advanced solid tumors, both as monotherapy and in combination with PD-(L)1 inhibitors, to improve the therapeutic index of CTLA-4 blockade.

Other names

tumor-selective CTLA-4 inhibitornext-generation anti-CTLA-4 mAbtumor-activated anti-CTLA-4 antibody