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.
KY-1044 (Alomfilimab; SAR 445256; 0-100ng/mL; 4 hours) causes human natural killer (NK) cells expressing hICOS (5:1 effector:target cell ratio) to induce potent ADCC-mediated killing (EC50=5.6 pmol/L)[1]. KY-1044 significantly induces the luciferase signal (EC50 of 0.15 nmol/L). A similar EC50 is obtained against mouse ICOS (0.53 nmol/L), rat ICOS (0.48 nmol/L), or cynomolgus monkey ICOS (0.22 nmol/L)[1].
KY-1044 (Alomfilimab; SAR 445256; 10 mg/kg; ip; twice a week for 3 weeks) mIgG2a (effector enable) monotherapy blocks tumor growth in lymphoma/myeloma tumor models[1]. In syngeneic mouse tumor models, KY-1044 depletes ICOShigh Treg and increases the intratumoral TEff:Treg ratio, resulting in increased secretion of IFNγ and TNFα by TEff cells[1].
References:
[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.