Abstract 1642: Evaluating in vivo efficacy of anti-VSIG4 antibodies in humanized B-hVSIG4 mice

Abstract

Abstract V-set and immunoglobulin domain containing 4 (VSIG4) protein is an immune checkpoint molecule that is related to the B7 family of immune regulatory proteins. B7 family members have been implicated in both positive and negative regulation of T cell activation, particularly VSIG4 is a known negative regulator of T cell proliferation and IL-2 production. Pathological consequences of VSIG4 expression are associated with inflammatory disorders, lung cancer development, high-grade glioma, and multiple myeloma, suggesting VSIG4 is a potential target for drug development. Therefore, Biocytogen developed humanized VSIG4 mice (B-hVSIG4 mice) by replacing the murine Vsig4 gene with the human VSIG4 gene through homologous recombination. Flow cytometry analysis showed human VSIG4 was detectable in peritoneal exudate macrophages (PEMs) in homozygous B-hVSIG4 mice compared to wild type mice. Additionally, percentages of T cells, B cells, NK cells, DCs, granulocytes, monocytes, macrophages, CD8+ T cells, CD4+ T cells and Tregs in homozygous B-hVSIG4 mice were similar to those in wild type mice, demonstrating that introduction of human VSIG4 in place of its mouse counterpart does not change the overall development, differentiation or distribution of these cell types. For in vivo efficacy evaluation of an anti-human VSIG4 antibody (Ab-A, synthesized in house) using B-hVSIG4 mice, mouse colon adenocarcinoma MC38 cells were subcutaneously implanted into homozygous B-hVSIG4 mice (female, 7-week-old, n=5). Mice were grouped and treated when the tumor volume reached approximately 100 mm3. Results showed that an anti-hVSIG4 antibody was efficient at inhibiting tumor growth in B-hVSIG4 mice. In conclusion, B-hVSIG4 mice are as a promising model for preclinical in vivo studies to assess pharmacodynamic of anti-hVSIG4 antibodies. Keywords: VSIG4, humanized mice, immune checkpoint molecule Citation Format: Ruili Lyu, Chengzhang Shang, Leila Kokabee, Yanhui Nie, Yi Yang. Evaluating in vivo efficacy of anti-VSIG4 antibodies in humanized B-hVSIG4 mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1642.