Abstract 4351: A sex-specific role of CD36 targeting therapy in colorectal cancer

Abstract Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. Based on distinct genetic characteristics, CRC can be classified into mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR). Unfortunately, current therapies, including immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor (VEGF) antibodies, showed limited efficacy in pMMR CRC patients. CD36, a fatty acid (FA) transporter and scavenger receptor, is broadly upregulated in cancers, and inhibiting CD36-mediated lipid uptake has shown therapeutic promise. We recently developed PLT012, a humanized IgG4 antibody targeting the lipid-binding pockets of CD36, with cross-species reactivity and a superior safety profile in monkeys. Importantly, PLT012 displayed significant therapeutic efficacy in liver cancers, potentially by shifting immunosuppressive tumor microenvironment. Here, we assess the therapeutic efficacy of PLT012 in pMMR CRC. Using the pMMR CRC mouse cell line SL4, our data showed that PLT012 effectively suppressed orthotopic CRC growth in female, but not male mice. This sex-specific effect correlated with higher CD36 expression in female mice, which we also observed in CRC patient samples. Interestingly, our preliminary data further suggested that CD36 was enriched in cancer-associated fibroblasts (CAFs) in a female-biased manner. Taken together, our findings highlight CD36 as a promising therapeutic target for pMMR CRC, particularly in female patients. Citation Format: Huanyu Wang, Jingying Zhou. A sex-specific role of CD36 targeting therapy in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4351.