Abstract 596: IOH-001, a novel CD47/PD-L1 bispecific antibody, enhances anti-tumor activity in solid tumors

Background: The survived cancer cells after cytotoxic chemotherapy are known to promote immune evasion phenotype by increasing the expression of PD-L1 and CD47. Targeting of CD47 and PD-L1 is predicted to overcome immune evasion by coordinately restoring each innate and adaptive immunity. IOH-001, a CD47/PD-L1 dual-targeting bispecific antibody, has been shown to activate immune cells in tumor microenvironment by blocking PD-1/PD-L1 signals that inhibit cytotoxic T-cells, while also blocking interaction with CD47/SIRPa between cancer cells and macrophages. We have investigated whether IOH-001 inhibits tumor growth via co-targeting tumor cells or not. Methods: To assess the function of IOH-001, a series of in vitro functional assays including cell surface binding, antibody-dependent cellular cytotoxicity (ADCC), phagocytosis assays and mixed lymphocyte reaction (MLR) assay were performed compared with the parent antibody. In vivo efficacy of IOH-001 was tested in colon cancer mouse models with human genes KI. Results: IOH-001 has been shown to be bound strongly to various types of PD-L1/CD47-expressing cancer cells including the ones in solid and hematological cancers. In most cancer cells, IOH-001 was demonstrated to have a lower EC50 than the parental antibodies and to be bound in a dose-dependent manner as well. Interestingly, IOH-001 also has shown the selectivity to bind only to cancer cells even under the conditions of co-culturing RBC and cancer cells. IOH-001 has induced phagocytosis of cancer cells by human blood CD14+ monocyte-derived macrophages. Since IOH-001 is an IgG1 type antibody, ADCC and IFN-r expression have been increased compared with the parental antibodies. Consistent with the in vitro data, IOH-001 has more strongly suppressed tumor growth than the combination treatment of the parental antibodies in a dose-dependent manner in syngeneic animal models. Moreover, the tumor of the CR mouse has been identified not to be re-generated in the re-challenge model. Conclusion: IOH-001, dual-blockage of anti-CD47 and anti-PD-L1, has shown the benefits in treating some solid tumors. Bispecific antibody IOH-001 is more likely to work better in targeting tumor cells than the combination of anti-CD47 and anti-PD-L1. Preclinical efficacy results of IOH-001 provide a strong rationale for assessing therapeutic potential in clinical studies. Citation Format: Jeong-kook Kim, A-Ra Jeon, Jihyun Park, Ji Yea Choi, Ji Eun Park, Sun Kwang Song, Ji Hye Choi, Heewook Shin, Ji Hye Lee, Ji Hye Yun, Yoen Hee Ahn, Heung Tae Kim. IOH-001, a novel CD47/PD-L1 bispecific antibody, enhances anti-tumor activity in solid tumors [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 596.