KY-1044

KY-1044 (Alomfilimab; SAR 445256) is a fully human IgG1 antibody targeting inducible costimulatory receptor (ICOS). KY-1044 depletes ICOShigh cells via antibody-dependent cellular cytotoxicity (ADCC) through the engagement of FcgRIIIa. KY-1044 act as a costimulatory molecule on cells expressing lower ICOS levels, such as CD8+ TEff cells (through FcgR-dependent clustering). KY-1044 exploit the differential expression of ICOS on T-cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

KY-1044 (Alomfilimab; SAR 445256; 0-100ng/mL; 4 小时)导致表达 hICOS (5:1 效应子: 靶细胞比例) 的人类自然杀伤 (NK) 细胞诱导有效的 ADCC 介导的杀伤 (EC50=5.6 pmol/L)[1]。 KY-1044 显着诱导荧光素酶信号 (EC50 为 0.15 nmol/L)，对小鼠 ICOS (0.53 nmol/L)、大鼠 ICOS (0.48 nmol/L) 或食蟹猴 ICOS (0.22 nmol/L) 获得了相似的 EC50[1]。

KY-1044 (Alomfilimab; SAR 445256; 10 mg/kg; 腹腔注射; 每周两次; 持续 3 周) mIgG2a (效应物启用) 单一疗法可阻断淋巴瘤/骨髓瘤肿瘤模型中的肿瘤生长[1]。 在同基因小鼠肿瘤模型中，KY-1044 耗尽 ICOShigh Treg 并增加瘤内 TEff:Treg 比率，导致 T 分泌 IFNγ 和 TNFα 增加 Eff 细胞[1]。 Animal Model: 8- to 10-week-old wild-type female Balb/C or C57BL/6J mice with A20 cells[1] Dosage: 200 μg (10 mg/kg) Administration: IP; twice a week for 3 weeks starting from 6 days following tumor cell implantation Result: Triggered an antitumor response, with more than 90% of the mice being free from measurable disease at the end of the study (day 42).

[1]. Richard C.A. Sainson, et al. An Antibody Targeting ICOS Increases Intratumoral Cytotoxic to Regulatory T-cell Ratio and Induces Tumor Regression. Cancer Immunol Res. 2020 Dec;8(12):1568-1582.