Abstract 6077: PLT012, a humanized CD36-blocking antibody, is effective for unleashing anti-tumor immunity and against liver metastasis

Abstract Tumor cells employ various mechanisms to evade immune surveillance, including metabolic modulation of the tumor microenvironment (TME). Lipid metabolic stress in the TME leads to upregulation of CD36 in tumor-infiltrating immune cells, impairing anti-tumor immunity by enhancing the survival and suppressive activity of regulatory T cells (Tregs) and promoting ferroptosis and exhaustion in CD8+ T cells. Here, we developed PLT012, a humanized anti-CD36 IgG4 antibody targeting the lipid-binding domain of CD36, with a remarkable safety profile and favorable pharmacokinetics demonstrated in cynomolgus monkey models. Moreover, PLT012 significantly reduces tumor growth and reprograms the immune landscape, enhancing CD8+ T cell effector functions while reducing Treg-mediated suppression. In both immunotherapy-sensitive and resistant hepatocellular carcinoma (HCC) models, PLT012 alone or in combination with PD-L1 blockade induces robust anti-tumor immunity. Importantly, in a syngeneic liver metastasis model, PLT012 decreases immunosuppressive populations, enhances effector T cell responses, and reduces ICI resistance. Notably, ex vivo studies with human HCC samples further confirm PLT012’s capacity to remodel the immune microenvironment. Taken together, these findings position PLT012 as a first-in-class immunotherapy targeting CD36, addressing critical challenges in HCC and liver metastasis treatment. Citation Format: Yi-Ru Yu, Sheue-Fen Tzeng, Zheng Meng, Jaeoh Park, Lana Kandalaft, Yun-Han Lin, Chin-Hsien Tsai, Ping-Chih Ho. PLT012, a humanized CD36-blocking antibody, is effective for unleashing anti-tumor immunity and against liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6077.