PLT012 is a humanized IgG4 antibody targeting CD36. PLT012 inhibits the lipid-binding domain of CD36. PLT012 blocks CD36-mediated metabolic adaptation in regulatory T cells (Tregs) and CD8 + tumor-infiltrating lymphocytes (TILs), thereby inhibiting tumor growth and shifting the tumor microenvironment from immunosuppressive to immunosupportive. PLT012 reduces intratumoral Tregs, enhances CD8 + T cell infiltration and cytotoxic function, and increases the abundance of progenitor-exhausted T cells. PLT012 exerts robust antitumor activity and synergizes with anti-PD-L1 or standard-of-care regimens (anti-VEGF + anti-PD-L1). PLT012 can be used for hepatocellular carcinoma, colorectal cancer and solid tumor research [1].
In Vivo, PLT012 promisingly exhibited anti-tumor responses in both Yumm1.7 melanoma and MC38 colorectal cancer models[1]. PLT012 (10 mg/kg, i.p. once) has the potential to restore anti-tumor immunity against HCC by targeting CD36-mediated immune regulations in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 (10 mg/kg, i.p., once every three days, 18 days) is capable of restoring anti-tumor responses in HCC and might also improve responsiveness to PD-1 blockade in the MYCOE/p53KO HCC mice model[1]. PLT012 (10 mg/kg, i.p., once every three days for 5 doses) remodels the immunosuppressive TME in β-catenin-mutant HCC, effectively activating anti-tumor T-cell immunity in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 significantly enhances anti-tumor efficacy when combination with an anti-PD-L1 monoclonal antibody or anti-VEGF and anti-PD-L1, and achieved a >70% overall positive response rate and a 45% complete response rate when combinates with anti-PD-L1 and anti-VEGF in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 restrains HCC progression under conditions of high dietary lipid intake in CTNNB1N90/MYCOE HCC-bearing mice, whether fed a standard chow diet (CD) or a high-fat Western (WD) diet[1]. PLT012 reprograms the tumor immune microenvironment, thereby restricting colon cancer liver metastasis and enhancing sensitivity to PD-1 blockade in mice MC38 xenografts models[1]. PLT012 (0-200 mg/kg, once a week, for 5 weeks) is well-tolerated in non-human primates (cynomolgus monkeys)[1].
In Vitro, PLT012 (0.001-100 μg/mL, 30 min) strongly inhibits the binding (IC50: 1.798nM) and uptake (IC50: 1.357nM) of fluorochrome-labeled oxidized low-density lipoprotein (oxLDL) in F293 cells (overexpress human CD36)[1]. PLT012 (5 mg/mL, 30 min) significantly represses oxLDL uptake in primary tumor-infiltrating immune cells, including myeloid cells, CD3+ T lymphocytes, and intratumoral Tregs isolated from MC38 tumor-bearing mice[1]. PLT012 can restore effector functions in exhausted T cells and induce CD8 T cell-mediated anti-HCC responses in isolated CD45+ tumor-infiltrating cells by using single-cell RNA sequencing (scRNA seq)[1]. PLT012 (2 days) effectively modulates the TME in HCCs by targeting CD36 in human HCC tumors, induces increase in CD8+ T cell percentage and GrB expression occurred in 45.4% of the patients[1].
References:
[1]. Tzeng SF, et al. PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Antitumor Immunity Against Liver Cancer and Liver Metastasis. Cancer Discov. 2025 Aug 4;15(8):1676-1696.
In Vivo, PLT012 promisingly exhibited anti-tumor responses in both Yumm1.7 melanoma and MC38 colorectal cancer models[1]. PLT012 (10 mg/kg, i.p. once) has the potential to restore anti-tumor immunity against HCC by targeting CD36-mediated immune regulations in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 (10 mg/kg, i.p., once every three days, 18 days) is capable of restoring anti-tumor responses in HCC and might also improve responsiveness to PD-1 blockade in the MYCOE/p53KO HCC mice model[1]. PLT012 (10 mg/kg, i.p., once every three days for 5 doses) remodels the immunosuppressive TME in β-catenin-mutant HCC, effectively activating anti-tumor T-cell immunity in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 significantly enhances anti-tumor efficacy when combination with an anti-PD-L1 monoclonal antibody or anti-VEGF and anti-PD-L1, and achieved a >70% overall positive response rate and a 45% complete response rate when combinates with anti-PD-L1 and anti-VEGF in CTNNB1N90/MYCOEHCC-bearing mice[1]. PLT012 restrains HCC progression under conditions of high dietary lipid intake in CTNNB1N90/MYCOE HCC-bearing mice, whether fed a standard chow diet (CD) or a high-fat Western (WD) diet[1]. PLT012 reprograms the tumor immune microenvironment, thereby restricting colon cancer liver metastasis and enhancing sensitivity to PD-1 blockade in mice MC38 xenografts models[1]. PLT012 (0-200 mg/kg, once a week, for 5 weeks) is well-tolerated in non-human primates (cynomolgus monkeys)[1].
In Vitro, PLT012 (0.001-100 μg/mL, 30 min) strongly inhibits the binding (IC50: 1.798nM) and uptake (IC50: 1.357nM) of fluorochrome-labeled oxidized low-density lipoprotein (oxLDL) in F293 cells (overexpress human CD36)[1]. PLT012 (5 mg/mL, 30 min) significantly represses oxLDL uptake in primary tumor-infiltrating immune cells, including myeloid cells, CD3+ T lymphocytes, and intratumoral Tregs isolated from MC38 tumor-bearing mice[1]. PLT012 can restore effector functions in exhausted T cells and induce CD8 T cell-mediated anti-HCC responses in isolated CD45+ tumor-infiltrating cells by using single-cell RNA sequencing (scRNA seq)[1]. PLT012 (2 days) effectively modulates the TME in HCCs by targeting CD36 in human HCC tumors, induces increase in CD8+ T cell percentage and GrB expression occurred in 45.4% of the patients[1].
References:
[1]. Tzeng SF, et al. PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Antitumor Immunity Against Liver Cancer and Liver Metastasis. Cancer Discov. 2025 Aug 4;15(8):1676-1696.