Novel arginase inhibitor alone and in combination with an immune check point inhibitor reduces tumour growth in murine experimental gliomas

Arginase as a Potential Biomarker of Disease Progression: A Molecular Imaging Perspective

“…Another novel Arg1 and Arg2 inhibitor, OATD-02 by OncoArendi Therapeutics SA (undisclosed structure, IC 50 < 50 nM [ 182 ]), is also expected to enter phase I trials mid-2020 to evaluate its ability to inhibit the proliferation and immune escape of cancer cells [ 172 ]. The combination of third-generation arginase inhibitors with other immune checkpoint inhibitors in a mouse glioma model recently suggested improving therapeutic response [ 183 ], which opens new doors for the development and use of arginase inhibitors. There is, for example, a potential for the clinical synergy between PD1/PDL1 checkpoint antagonists combined with arginase inhibitors to remodel pathologically impaired M2 macrophage compartments in several tumors [ 184 , 185 ].…”

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression

“…Our data agree with other studies showing the prognostic potential of ARG2, 22 , 43 , 44 , 45 while a recent study showed that ARG2 promotes melanoma progression and metastasis through STAT3 signalling, also involved in BM. 46 , 47 Since arginase has been identified as a potential biomarker of disease progression, investigating the therapeutic efficacy of arginase inhibitors as monotherapy or in combination with PD-1/PD-L1 inhibitors has been of great research interest 38 , 40 , 48 , 49 , 50 , 51 , 52 and a number of clinical trials are ongoing ( Supplementary Table S2 , available at https://doi.org/10.1016/j.esmoop.2022.100636 ) in advanced solid tumours and glioblastoma. Finally, we observed that there was a significant difference between the transcript levels of ARG2 and cytotoxic cells and T cells in both BC and BCBM samples ( Figure 4 ) indicative of a depleted T-cell response.…”