Abstract 6340: Preclinical development of a monoclonal antibody targeting CD24 as cancer immunotherapy

Abstract CD24 is a novel immune checkpoint that suppresses activation of macrophages, natural killer (NK) cells, T cells and B cells by binding to inhibitory receptor Siglec-10. CD24 is highly expressed on cancers of genitourinary (GU) and gastrointestinal (GI) systems, breast, and lung. High expression of CD24 is also known to be associated with poor prognosis for many types of cancers including breast, lung, GU and GI systems, bone, skin and brain. Mouse models of breast and lung cancer in literature revealed that CD24 attenuation in vivo leads to tumor inhibition and prolonged survival. To address the limited (~25%) overall response rate (ORR) of approved PD-1/PD-L1 antibodies for solid tumors, we developed IMM47, an IgG1 antibody that differentially targets phagocytosis and cytotoxicity onto CD24-expressing cancer cells. At doses between 3 mg/kg to 10mg/kg, IMM47 significantly reduced tumor volume in a MC38 mouse model of colon cancer. Mice treated with 10mg/kg IMM47 produced tumor-specific immune response that prevented growth of re-inoculation of colon cancer cells. Further mechanism of action studies showed that IMM47 selectively and differentially increased M1 spleen macrophages quantity to 7-10 folds higher in that induced by PBS control. In contrast, IMM47 only increased M2 spleen macrophages to less than 1.5 folds higher than induced by PBS control. Expression of MHC II in M1 macrophages was also increased in IMM47-treated mice, suggesting significant activation and antigen presentation by macrophages. Our data has also confirmed that IMM47 specifically binds to and induces ADCC (antibody-dependent cellular cytotoxicity),ADCP (antibody-dependent cellular phagocytosis), and CDC (complement-dependent cytotoxicity) against a variety of cancer cells. Taken together, our data show that targeting CD24 on tumor cells using our IMM47 antibody may serve as potent immunotherapy for multiple cancer indications. Citation Format: Wenzhi Tian, Song Li, Dianze Chen, Dandan Liu, Huiqin Guo, Chunmei Yang, Li Zhang, Wei Zhang, Xiaoping Tu, Liang Peng, Gui Zhao, Ruliang Zhang, Fan Zhang, Frank X. Gan. Preclinical development of a monoclonal antibody targeting CD24 as cancer immunotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6340.