KY-1044 (Alomfilimab; SAR 445256) is a fully human IgG1 monoclonal antibody that targets the inducible costimulatory receptor (ICOS). This compound selectively depletes cells with high ICOS expression through antibody-dependent cellular cytotoxicity (ADCC), mediated by FcγRIIIa engagement. Meanwhile, it acts as a costimulatory molecule for cells with lower ICOS levels, such as CD8+ T Effector cells, via FcγR-dependent clustering. KY-1044 leverages varying ICOS expression levels across T-cell subsets to enhance the intratumoral immune milieu and reinvigorate antitumor immune responses [1].

KY-1044（Alomfilimab; SAR 445256; 0-100ng/mL; 4小时）在hICOS（5:1 效应子:靶细胞比率）表达的人类NK细胞上引发高效ADCC介导的细胞杀伤（EC50=5.6 pmol/L）[1]。

KY-1044 (Alomfilimab; SAR 445256; 10 mg/kg; 腹腔注射; 每周两次; 持续3周)作为mIgG2a（效应物启用）的单一疗法，在淋巴瘤/骨髓瘤肿瘤模型中能够有效抑制肿瘤生长[1]。在同基因小鼠模型中，该化合物能够减少ICOS high Treg的数量，并提高瘤内T Eff :Treg比率，促进T细胞分泌IFNγ和TNFα，从而增强Eff细胞的功能[1]。