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.
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.