Abstract
Abstract The CD47/Signal regulatory protein α (SIRPα) axis regulates myeloid cell activation and functions as a crucial myeloid specific immune checkpoint. CD47 is highly expressed on many different types of cancer and upon binding with SIRPα which is abundantly expressed on myeloid cells, transduces inhibitory signals that protect cancer cells from phagocytosis by macrophages and other myeloid cells. Therefore, antibodies that block CD47 and SIRPα binding become encouraging tools for cancer immunotherapy. Biocytogen developed humanized SIRPα B-NDG mice and double humanized SIRPα/CD47 B-NDG mice to provide solid platforms for in vivo efficacy assessment of SIRPα antibodies with or without other immune checkpoint regulators. These mice have a B-NDG mouse background (completely lacking mature T, B and NK cells and were deficient in cytokine signaling) and express human SIRPα protein only or with human CD47 IgV domain and no mouse counterpart expressed. Raji-Luc cells were injected into these mouse models for tumor xenografting and anti-tumor efficacy of anti SIRPα antibody in combination with other antibodies was evaluated. The results showed that the combination of antibodies could effectively control tumor growth in the two mouse models. In addition, B-NDG hSIRPα/hCD47 mice can be used for toxicity assessment for SIRPα or CD47 antibodies. In summary, both B-NDG hSIRPA and B-NDG hSIRPA/hCD47 mice are promising models for preclinical in vivo evaluation of SIRPα antibodies and combined therapy. Citation Format: Yuting Hu, Lei Zhao, Yujie Liu, Li Hui, Zhaoxue (Luke) Yu. Humanized SIRPA and double humanized SIRPA/CD47 B-NDG mouse models are promising tools for anti-SIRPα antibody in vivo efficacy studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 496.
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