{
  "abstract": "Background Tumor cells evade immune surveillance by remodeling the tumor microenvironment (TME), with lipid metabolic stress emerging as a key driver of immunosuppression. Lipid metabolic stress drives CD36 upregulation on tumor-infiltrating immune cells, promoting immunosuppressive activity, T cell exhaustion, and loss of effector function. These features contribute to resistance against immune checkpoint inhibitors. We have previously shown that PLT012, a humanized anti-CD36 antibody, blocks fatty acid uptake and reprograms the TME, reducing suppressive cell populations while enhancing effector functions in both inflamed and immune-cold HCC models. 1 These findings highlight CD36 as a promising immunometabolic target for lipid-enriched cancers (figure 1).Methods PLT012, a humanized anti-CD36 antibody, was developed via phage display, followed by affinity maturation and developability optimization. It exhibits a favorable safety and pharmacokinetic profile in non-human primates. The therapeutic efficacy and durable immune response of PLT012 were evaluated in both immunotherapy-sensitive and -resistant HCC models, as well as in a syngeneic MC38 liver metastasis model. Ex vivo studies using freshly resected human HCC and liver metastasis tissues further validated immune modulatory effects.Results PLT012 significantly reduced tumor growth and remodeled the immune landscape across models. In HCC, PLT012 enhanced CD8 + T cell effector function while reducing Treg-mediated suppression, both as monotherapy and in combination with anti-PD-L1. In the liver metastasis model, PLT012 reduced tumor burden at both hepatic and subcutaneous sites, accompanied by decreased M2 macrophages and Tregs, and increased CD8+ T cell infiltration. Ex vivo human tumor cultures confirmed these immune changes. PLT012 also mitigated ICI resistance driven by liver metastases and resensitized tumors to anti-PD1 therapy. Importantly, PLT012 treatment not only elicited remarkable tumor-control immunity, leading to complete tumor clearance, but also established immune memory for long-term protection, as evidenced by reduced incidence of rechallenge tumors and strong immune recall responses.Conclusions PLT012 is a first-in-class CD36-targeting immunotherapy that reprograms the TME by disrupting immunosuppressive lipid metabolism. By enhancing effector T cell function and reducing suppressive cell populations, PLT012 overcomes ICI resistance and induces durable tumor control in both HCC and liver metastases. These findings underscore the promise of immunometabolic targeting in lipid-enriched malignancies.Reference Sheue-Fen Tzeng#, Yi-Ru Yu#, …, Ping-Chih Ho (2025) . PLT012, a humanized CD36-blocking antibody, is effective for unleashing antitumor immunity against liver cancer and liver metastasis. Cancer discovery. #, equal contribution.Abstract 1205 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Pilatus Biosciences, Lausanne, Switzerland"
      ],
      "name": "Yi-Ru Yu"
    },
    {
      "affiliations": [
        "National Defense Medical Center/NDMC, Taipei, Taiwan"
      ],
      "name": "Sheue-Fen Tzeng"
    },
    {
      "affiliations": [
        "Elixiron Immunotherapeutics, Taipei, Taiwan"
      ],
      "name": "Huey-Wen Hsiao"
    },
    {
      "affiliations": [
        "Elixiron Immunotherapeutics, Taipei, Taiwan"
      ],
      "name": "Hung-Kai Chen"
    },
    {
      "affiliations": [
        "Pilatus Biosciences, Epalinges, Switzerland"
      ],
      "name": "Yun-han Lin"
    },
    {
      "affiliations": [
        "National Defense Medical Center/NDMC, Taipei, Taiwan"
      ],
      "name": "Chin-Hsien Tsai"
    },
    {
      "affiliations": [
        "University of Lausanne and University Hospital of Lausanne, Epalinges, Switzerland"
      ],
      "name": "Ping-Chih Ho"
    }
  ],
  "title": "1205 PLT012, a humanized CD36-blocking antibody, induces durable anti-tumor immunity via immunometabolic reprogramming",
  "uid": "f2d63b23-2ca7-5ddd-adc2-0dcbe2d346b8"
}