cellular activity. In vivo, OATD-02 showed good pharmacological properties and significant antitumor efficacy as a monotherapy in multiple tumor models. Combining OATD-02 with PD-L1 and IDO inhibitors exhibited greatly increased antitumor efficacy. The efficacy correlated with sustained pharmacodynamic effects: 3-6 fold increase in plasma and tumor arginine levels and suppression of tumor arginase activity. The arginine plasma levels exceeded several fold concentration required for the maximal stimulation of T cell proliferation. Induction of inflammatory markers (IFN-gamma, CD94, CD3) in tumors confirmed reversal of immunosuppression. Conclusions: The results provide a rationale for the clinical development of OATD-02 as a cancer immunotherapy.
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