2. Academic Validation
  3. PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Antitumor Immunity Against Liver Cancer and Liver Metastasis

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. doi: 10.1158/2159-8290.CD-24-1409.
Sheue-Fen Tzeng # 1 2,  Yi-Ru Yu # 3 4 5,  Jaeoh Park 4 5,  Janusz von Renesse 4 5,  Huey-Wen Hsiao 6,  Chen-Hsuan Hsu 2,  Josep Garnica 4 5 7,  Jintian Chen 8,  Lu-Ting Chiu 3,  Jonas Santol 9 10 11,  Tse-Yu Chen 12 13,  Pei-Han Chung 6,  Lana E Kandalaft 14,  Patrick Starlinger 10 15 16,  Rodney Cheng-En Hsieh 12 13,  Ming-Chin Yu 17,  Pei-Wen Hsiao 18,  Santiago J Carmona 4 5 7,  Hung-Kai Chen 6,  Zhen Meng 19,  Yun-Han Lin 3,  Jingying Zhou 8,  Chin-Hsien Tsai 2 20 21,  Ping-Chih Ho 4 5
Affiliations

Affiliations

  • 1 Tumor Immune Analysis Core, Office of Research & Development, Taipei Medical University, Taipei, Taiwan.
  • 2 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
  • 3 Pilatus Biosciences SA, Epalinges, Switzerland.
  • 4 Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland.
  • 5 Ludwig Institute of Cancer Research Lausanne Branch, Epalinges, Switzerland.
  • 6 Elixiron Immunotherapeutics Inc., Taipei, Taiwan.
  • 7 Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • 8 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
  • 9 Department of Surgery, HPB Center, Vienna Health Network, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.
  • 10 Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
  • 11 Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
  • 12 Department of Medical Imaging and Radiological Sciences, Cancer Genome Research Center, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan.
  • 13 Department of Radiation Oncology, Cancer Genome Research Center, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan.
  • 14 Department of Oncology, University of Lausanne, CHUV, Lausanne, Switzerland.
  • 15 Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria.
  • 16 Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
  • 17 Department of surgery, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan.
  • 18 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
  • 19 Society of Toxicology, Reston, Virginia.
  • 20 International Ph.D./Master Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • 21 The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
  • # Contributed equally.
PMID: 40294022 DOI: 10.1158/2159-8290.CD-24-1409
Abstract

Tumor cells develop various strategies to evade immune surveillance, one of which involves altering the metabolic state of the tumor microenvironment. In response to metabolic stress in the tumor microenvironment, several tumor-infiltrating immune subsets upregulate CD36 to take up lipids. This leads to impaired antitumor immunity, as intratumoral regulatory T cells exhibit increased survival and suppressive activity, whereas CD8+ T cells become more susceptible to Ferroptosis and exhaustion. In this study, we develop a humanized anti-CD36 IgG4 antibody, PLT012, against the lipid-binding domain of CD36 with excellent safety and favorable pharmacokinetic features in mice and cynomolgus monkeys. PLT012 alone or in combination with PD-L1 blockade or standard-of-care immunotherapy results in robust antitumor immunity in both immunotherapy-sensitive and -resistant hepatocellular carcinomas (HCC). Notably, PLT012 also reprograms the immune landscape of human HCC ex vivo. Our findings provide proof-of-concept evidence that PLT012 reprograms antitumor immunity in HCC, positioning it as a first-in-class immunotherapy targeting CD36.

Significance: Despite the success of Cancer immunotherapies, like immune checkpoint inhibitors, many patients still fail to demonstrate significant responses because of metabolic constraints in tumors. PLT012 rejuvenates antitumor immunity by targeting metabolic pathways to reprogram the immune landscape of liver Cancer and liver metastasis, with potential to influence future HCC immunotherapy.

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