470 Botensilimab, an Fc-enhanced CTLA-4 antibody, enhances innate and adaptive immune activation to promote superior anti-tumor immunity in cold and I-O refractory tumors

Next-generation CTLA-4 targeting molecules and combination therapy: promising strategies for improving cancer immunotherapy

“…In preclinical models, Fc-enhancement provided a more favorable environment for anti-tumor T cells to eliminate cancer cells. 7 …”

“… 8 , 9 Botensilimab’s novel FcyR-dependent mechanisms of action promoted superior priming and activation of T cells, as indicated by the expansion of new peripheral T cell clones in patients with advanced solid cancers. 7 Notably, botensilimab preferentially reduced suppressive intratumoral Tregs, a mechanism that remains controversial for conventional anti-CTLA-4. 7 Lastly, clinical response to botensilimab was independent of tumor neoantigen-burden and FCGR3A allele status, 7 unlike that reported for ipilimumab.…”

“… 7 Notably, botensilimab preferentially reduced suppressive intratumoral Tregs, a mechanism that remains controversial for conventional anti-CTLA-4. 7 Lastly, clinical response to botensilimab was independent of tumor neoantigen-burden and FCGR3A allele status, 7 unlike that reported for ipilimumab. 5 …”

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer

“…Botensilimab (BOT) is an Fc-enhanced next-generation anti– cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody [ 4 ]. It is a novel fragment crystallizable molecule and its binding with Fc gamma receptor IIIA (FcyRIIIA) leads to differential immune effector functions promoting a response in otherwise so called ‘cold tumors’ [ 5 ]. The multi-functionality of the CTLA-4 inhibitor is considered responsible for the differential efficacy and toxicity profile seen with the BOT [ 4 , 5 ].…”