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HiFiBiO and Gustave Roussy Researchers Demonstrate the Contribution of Galectin-9 (Gal-9) in Tumor Immune Escape

Research published in Nature Scientific Reports demonstrates the ablation of Gal-9 produced by malignant cells is linked with reduction in tumor growth in a MB49 murine model.

Paris, France – March 19, 2021 – HiFiBiO Therapeutics in collaboration with researchers at Gustave Roussy have uncovered galectin-9’s contribution to tumor immune escape in a MB49 murine model. By comparing isogenic clones – either positive or negative for gal-9 – in both syngeneic mice and nude mice, the researchers linked tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. The results are detailed in an article on Nature Scientific Reports.

Gal-9 has been shown in previous reports to play a major role in the immune system, acting like a cytokine with mainly immunosuppressive effects. Normally, gal-9 is expressed at low levels in most tissues and organs but is ramped up under inflammatory conditions. In the context of cancer, the contribution of gal-9 to immune evasion has been reported in several malignancies including lung, breast and pancreatic carcinomas, melanomas and acute myeloid leukemias. However, the exact role of gal-9 in the malignant process has been difficult to discern, especially the respective contributions of gal-9 produced either by malignant cells or infiltrating cells.

The researchers (Gustave Roussy, CNRS and Université Paris-Saclay – UMR9018) used a gene editing approach to create isogenic gal-9 positive and gal-9 negative clones derived from the murine bladder carcinoma cell line MB49. Gal-9 gene ablation made MB49 cells more sensitive to an anti-tumor immune response and serial transplants further increased this sensitivity. Gal-9 ablation also led to enhanced T-cell activity and transcription of genes related to interferon-γ response. This response was not observed when the serial transplantation was made in nude mice.

The results further support the development of our HFB2009 program, which includes a potential first-in-class anti-gal-9 neutralizing antibody for AML and solid tumors which has demonstrated single agent anti-tumor activity in a mouse cancer model.

“We were excited to further uncover the important role of gal-9 in tumor immune escape and develop a novel experimental system shedding new light on the underlying mechanisms,” said Dr Pierre Busson, “working closely with HFiBiO enables us to explore potential therapeutics implications.”

Liang Schweizer, PhD, CEO and CSO for HiFiBiO Therapeutics said, “These results further support our therapeutic rationale for our HFB2009 program as we continue to advance this exciting program. We are actively working with top academic institutions such as Gustave Roussy to explore and validate further disease mechanisms. This publication is another showcase of our open innovation strategy for developing novel therapeutics for unmet needs.”

 

About HiFiBiO Therapeutics

HiFiBiO Therapeutics is transforming the field of immunotherapy by combining proprietary single-cell profiling technologies with advanced data intelligence and deep knowledge of immune system biology. This approach enables the development of novel antibody therapies that are paired with biomarkers to predict patient response. HiFiBiO Therapeutics is working actively to address unmet medical needs around the world through its own innovative pipeline programs and open-innovation partnerships with world-renowned industry and academic researchers. The company’s strong global footprint features cutting-edge laboratories on three continents, in Cambridge, Mass., Paris, Shanghai, and Hong Kong. To learn more, please visit www.hifibio.com.

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