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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]. | [in vivo]
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]. | 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).
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| [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. DOI:10.1158/2326-6066.CIR-20-0034 |
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