Abstract LB348: Discovery and in vitro efficacy validation of anti-CD39 monoclonal antibody for improving the tumor microenvironment

Abstract

Abstract In the tumor microenvironment (TME), the accumulation of adenosine inhibits anti-tumor immune responses, thereby reducing the effectiveness of immune-based cancer therapies. CD39 is involved in inducing excessive adenosine production in tumor cells and immune cells, causing an immune-suppressive environment. As a result, cancer cells are able to evade the immune system, and immune cells are impaired in their ability to kill cancer cells. Therefore, the discovery of outstanding antibodies targeting CD39 has great potential for cancer immunotherapy. To this end, we have discovered antibodies that effectively inhibit the hydrolysis of ATP to adenosine.We confirmed the binding affinity of the anti-CD39 mAb to the CD39 antigen. BLI measurements revealed that anti-CD39 mAb had binding kinetics of KD = 9.40 x 10-11 M, which is better than those of comparative antibodies, competitor 1 (2.39x10-10 M) and competitor 2 (2.27x10-9 M). The cell binding affinity of anti-CD39 mAb was evaluated using SK-MEL-28 cells, which endogenously express high levels of surface CD39. The results showed that the anti-CD39 mAb exhibited superior cell binding affinity compared to the two comparative antibodies. Furthermore, anti-CD39 mAb demonstrated greater efficacy in inhibiting ATP hydrolysis by membrane CD39 and soluble CD39 when compared to the comparative antibodies. In vitro functional assays using human PBMCs demonstrated that inhibiting CD39 enhances T cell proliferation. The anti-CD39 mAb showed superior efficacy in promoting proliferation in CD4+ cells compared to the competitor antibody. Similarly, in CD8+ cells, anti-CD39 mAb exhibited more efficacy compared to competitor 1 antibody. In conclusion, our data indicates that anti-CD39 mAb exhibits excellent characteristics, including superior antigen binding affinity, inhibitory efficacy of ATP hydrolysis and promotion of T cell proliferation. In the future, we will validate the efficacy and stability of this antibody in preclinical studies. The use of this antibody is expected to contribute to immune-based cancer therapy by inhibiting the generation of adenosine in the tumor microenvironment. Citation Format: Seonmi Yu, Wanki Park, Jaeho Song, Sooyoung Kim, Bumchan Park. Discovery and in vitro efficacy validation of anti-CD39 monoclonal antibody for improving the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB348.