3.3CD39 mAb combined with TIGIT mAb
TIGIT is an inhibitory receptor and is expressed on lymphocytes, it has recently attracted attention as the latest target for tumor immunotherapy. It shows interplay between TIGHT and CD155, which is expressed on APCs or tumor cells, reducing T and NK cell function. TIGIT, a significant inhibitor of antitumor response, blocks the tumor immune cycle in multiple steps[56-58]. Several studies have shown that blocking TIGIT can prevent various solid tumors and hematologic malignancies. In AML, inhibition of CD39 combined with TIGIT can apparently increase AML cell lysis in 2/3 cell lines, and combined inhibition of TIGIT and CD39 significantly improved NK cell killing activity in vitro, thus further enhancing NK cell killing effect on AML cells[37, 38, 59].Due to the difference in the expression of the TIGIT/PVRIG axis and CD39 in different NK cell subsets, joint blocking of these pathways may enhance the cytotoxic function of different NK cell subsets in vivo. In addition, it has been preliminarily proved that RORγ agonists can simultaneously reduce the expression of CD39, TIGIT and other immune checkpoints on lymphocytes, and integrate multiple anti-tumor mechanisms into one therapy, which can not only enhance immune activity, but also reduce immunosuppression, thus effectively inhibiting tumor growth[60].