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].