A novel CSF-1R neutralizing antibody, DCB-AB21, inhibits colony stimulating factor 1 receptor signaling activity

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.135-135.19
• Main Authors: Chen-Hsuan, HO, Liao, Chu-Bin, Chen, Yu-Kai, Huang, Chen-Wei, Yang, Tze-Pin
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.135.19

Tumor-associated macrophages (TAMs) represent the major cell components of immune infiltrate in solid tumors, and it has been reported that high TAMs density is associated with poor clinical prognosis. Within the tumor microenvironment, TAMs rely on signaling through colony stimulating factor 1 receptor (CSF-1R)/CSF-1 axis for various tumor promoting processes such as tumor growth, angiogenesis, and metastasis. Therefore, decrease of TAMs density in tumors through CSF-1R inhibition is considered an attractive therapeutic target for drug development. In this study, we report that a novel anti-CSF-1R monoclonal antibody DCB-AB21 which specifically binds to CSF-1R and inhibits CSF-1R downstream signaling. Anti-proliferative activity was measured on murine Ba/F3 cells engineered to be dependent on CSF-1R, and our results showed DCB-AB21 can blocks the CSF-1 and IL-34-induced cell proliferation. Potent inhibition of CSF-1R-dependent signaling was observed in the Ba/F3 CSF-1R driven model cells, and in human THP-1 leukemia monocytic cell lines. Humanization engineering further improves this antibody’s affinity and anti-proliferative efficacy. The discovery of novel binding epitope of DCB-AB21 differentiates itself from the current CSF-1R targeting antibodies testing in clinical trials. In vivo efficacy of DCB-AB21 is now in progress. Together, these data demonstrate that DCB-AB21 can potently inhibit CSF-1R in cellular contexts and that this activity has the potential to induce a phenotypic effect on macrophages. These data suggest that DCB-AB21 is a promising new agent with possibility to combine with immune checkpoint inhibitors to relief macrophage-dependent immune suppression and would yield clinical benefit.