ADI-PEG 20 Can Boost Anti-Tumor Immune Surveillance
SAN DIEGO, Oct. 24, 2016 /PRNewswire/ -- Polaris Group announced today that ADI-PEG 20, arginine deiminase formulated with polyethylene glycol, can boost anti-tumor immune surveillance according to research presented by Polaris at the 2016 American Association for Cancer Research Tumor Immunology and Immunotherapy conference in Boston. These findings suggest that ADI-PEG 20 could potentially enhance the activity of anti-tumor immune therapies, including checkpoint inhibitors.
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To investigate the potential effect of ADI-PEG 20 on immune cells, healthy human peripheral blood mononuclear cells were treated with ADI-PEG 20 under resting and activation conditions and were characterized by immune cell phenotyping using flow cytometry. Researchers found that under stimulation conditions ADI-PEG 20 treatment markedly boosted T cell activation (as measured by CD69 expression) while moderating T cell exhaustion (CTLA-4 and PD-1 levels remained low, similar to that at a resting state). Moreover, ADI-PEG 20 reduced accumulation of regulatory T cells, which are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. As such, it was hypothesized that ADI-PEG 20 may improve immunogenicity of non-immunogenic tumors.
The poorly immunogenic mouse melanoma B16-F10 model was used to test the hypothesis. Analysis of the tumor sections revealed that five out of six ADI-PEG 20 treated animals had a large number of T cells in their tumors; only one ADI-PEG 20 treated mouse had very little tumor T cell infiltrate, similar to the non-treated controls, demonstrating that ADI-PEG 20 can improve tumor immunogenicity. ADI-PEG 20 also inhibited growth of the B16-F10 tumor in vitro and in vivo.
"We are excited about the discovery of ADI-PEG 20's ability to regulate cellular immune response, thereby expanding its mechanism of action for its anti-tumor activity. We are conducting further research to assess which combinations of ADI-PEG 20 with PD1/PD-L1 blockers will further enhance these drugs' anti-tumor efficacy," said John Bomalaski, M.D., Executive Vice President of Medical Affairs at Polaris Pharmaceuticals, Inc.
About ADI-PEG 20
ADI-PEG 20 is a biologic being developed by Polaris Group to treat cancers, especially those carrying a major metabolic defect that renders such cancer cells, unlike normal cells, unable to internally synthesize arginine. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, it is believed these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient's normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine dependency.
About Polaris Group
Polaris Group is a multinational biotechnology company specializing in the research and development of novel pharmaceuticals to treat cancer. The company's lead therapeutic, ADI-PEG 20, is a novel biologic in late stage clinical development. It has been tested in more than twenty clinical trials globally for a wide variety of cancers, including hepatocellular carcinoma, mesothelioma, pancreatic cancer, non-small cell lung cancer, melanoma, acute myeloid leukemia and others. As a fully integrated company, Polaris is engaged in applying protein structure-based drug design technology to develop novel drug candidates for cancers, conducting clinical studies at top-tier cancer centers worldwide, and manufacturing all clinical materials at its certified cGMP facilities in northern California.
For additional information please visit www.polarispharma.com.
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