SAN DIEGO—Polaris Group announced recently that ADI-PEG 20, arginine deiminase formulated with polyethylene glycol, can boost antitumor 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 antitumor 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 antitumor activity. We are conducting further research to assess which combinations of ADI-PEG 20 with PD1/PD-L1 blockers will further enhance these drugs’ antitumor efficacy,” said Dr. John Bomalaski, executive vice president of medical affairs at Polaris Pharmaceuticals Inc.
