H3 Biomedicine and University of British Columbia Scientists Report Preclinical Data Describing Immune Evasion Mechanism in Muscle-Invasive Bladder Cancer

Article published in current issue of Nature Communications details that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC

CAMBRIDGE, Mass. & VANCOUVER, British Columbia--()--H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of precision medicines for oncology and a member of Eisai’s global Oncology Business Group, and the Vancouver Prostate Centre and Vancouver Coastal Health Research Institute (VCHRI) announced today, that data on one of H3’s pre-clinical programs focusing on muscle-invasive bladder cancer, has been published in the current issue of Nature Communications. The paper, which is titled “Evasion of immunosurveillance by genomic alterations of PPARγ/RXRα in bladder cancer,” can be found at http://www.nature.com/articles/s41467-017-00147-w.

“The fact that PPARγ and its binding partner RXRα can so potently suppress immune cell infiltration into tumors may explain the lack of response to immune-directed therapies in this class of tumor”

“While the majority of the field was focused on manipulating function of immune cells, H3 explored a novel paradigm by focusing on tumor cells and their potential to effectively inhibit immune cell function,” said Ping Zhu, Ph. D., Executive Director of Target Discovery at H3 Biomedicine. “Years ago when we built our immuno-oncology platform, our hope was to identify genomically-altered genes in tumors that may extend their reach beyond the tumor cell to influence immune response.”

Muscle-invasive bladder cancer is an aggressive form of cancer with limited therapeutic options available to patients. In the past year, agents designed to target the immune system have been approved for bladder cancer; however, the median survival in patients with second-line disease remains less than a year, and less than a third of first-line patients respond to treatment. Based on this unmet need, researchers at H3 Biomedicine took a novel approach to understanding how tumors can overcome the debilitating effects of the immune system.

The publication in Nature Communications reports that a significant proportion of bladder tumors showing focal amplification of PPARγ and hotspot mutations in RXRα, lead to hyperactivity of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. Deep molecular characterization in cell lines and clinical samples also showed that tumors increased the activity of this pathway to prevent immune cells from infiltrating the tumors increasing the survival of the tumor cells. In collaboration with a team of Drs. Mads Daugaard and Peter Black at the University of British Columbia, the Vancouver Prostate Centre and VCHRI, the scientists further confirmed the association of PPARγ pathway activity with immune evasion in additional cohorts of bladder tumors.

“The fact that PPARγ and its binding partner RXRα can so potently suppress immune cell infiltration into tumors may explain the lack of response to immune-directed therapies in this class of tumor,” said Manav Korpal, Ph. D., Senior Investigator at H3 Biomedicine. “One way to potentially combat this class of tumor is to combine immune-directed therapies with compounds that modulate PPARγ function.”

About H3 Biomedicine Inc.

H3 Biomedicine is a Cambridge, Massachusetts-based biopharmaceutical company specializing in the discovery and development of precision oncology treatments, which was established as a subsidiary of Eisai’s U.S. pharmaceutical operation Eisai Inc. Leveraging this collaboration with Eisai Co., Ltd., who through this partnership provides essential research funding and access to the capabilities and resources of this global pharmaceutical company, H3 Biomedicine combines long-term vision with operational independence. Using modern synthetic chemistry, chemical biology, and human genetics, H3 Biomedicine seeks to bring the next generation of cancer treatments to market with the goal of improving the lives of patients. For more information, please visit www.h3biomedicine.com.

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