Article Text

Download PDFPDF

836 A novel PD-L1 antibody-IL10 fusion protein, PTL011, exhibits synergized therapeutic effect in hepatocellular carcinoma mouse model
  1. Chin-Hsien Tsai1,
  2. Sheue-Fen Tzeng2,
  3. Yi-Ru Yu3,
  4. Huey-Wen Hsiao4,
  5. Jaeoh Park5,
  6. Pandelakis Koni6,
  7. Hung-Kai Chen4,
  8. Lana Kandalaft7,
  9. Claudia Lengerke8 and
  10. Ping-Chih Ho3
  1. 1University of Lausanne, Taipei City, Taiwan
  2. 2National Defense Medical Center, Taipei City, Taiwan
  3. 3University of Lausanne, Lausanne, Switzerland
  4. 4Elixiron Immunotherapeutics, Taipei, Taiwan
  5. 5Ludwig Institute for Cancer Research Lausanne Branch, Epalinges, Switzerland
  6. 6Elixiron Immunotherapeutics, Inc., Larkspur, CA, USA
  7. 7University Hospital of Lausanne (CHUV), Lausanne, Switzerland
  8. 8University Hospital Tuebingen, Tuebingen, Germany


Background Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. The liver’s immune function is known for its tolerance and immunosuppression, making it difficult for immunotherapy such as immune checkpoint inhibitors (ICIs) to be effective. Consequently, immunotherapy has limited success in treating HCC. The T-cell response is a crucial factor in this process, and therapies that counteract these immunosuppressive mechanisms and enhance tumor-specific immunity can significantly improve clinical outcomes for HCC patients. A study found that interleukin-10-Fc fusion protein can rejuvenate terminally exhausted CD8+ tumor-infiltrating lymphocytes by promoting oxidative phosphorylation. In addition, overexpression of IL-10 or treatment with pegylated IL-10 (PEG-IL-10) has led to tumor rejection and long-lasting tumor immunity in mouse models of cancer.

Methods This study focuses on a newly developed humanized PD-L1 antibody merged with IL-10 protein, which we have named PLT011. Our goal is to enhance ICI treatment and more effectively deliver IL-10 into the tumor to induce superior anti-tumor responses and prevent potential complications. To evaluate the efficacy of PLT011, we conducted tests on a murine model of hepatocellular carcinoma caused by expression of b-catenin and Myc through hydrodynamic injection. To confirm tumor suppression, we compared the effectiveness of PLT011 with that of the anti-PD-L1 antibody, IL-10-Fc, and a combination of both IL-10-Fc and anti-PD-L1 antibody. Additionally, we utilized FACS to verify the immune cell profile in the HCC murine model.

Results The use of PLT011 treatment is more effective in suppressing tumor growth than using either monotherapy or combined treatment. Additionally, this treatment does not cause significant toxicity in mice. It is important to note that PLT011 treatment also increases the population of both TCF1+/PD1- Progenitor exhausted T cells and TCF1-/PDL1+ Terminal exhausted T cells.

Conclusions PLT011 treatment triggers the activation of tumor-specific CD8 T cells and potentially restores the function of exhausted T cells in the tumor by reprogramming the metabolism. In this preclinical model, PTL011 has shown promising results in treating HCC with lower toxicity, indicating that this new approach could benefit more patients receiving immunotherapy.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.