5.3A2aR mAb combined with TIGIT mAb
The frequency of TIGIT+NK cells in patients’ blood was
negatively related to the prognosis of AML. Compared with healthy
subjects, AML patients had abnormal NK cell populations in peripheral
blood (PB) and bone marrow (BM), which were shown as increased frequency
of TIGIT+, PVRIG+, CD39+ and CD69+NK cells. This makes TIGIT a target
for AML treatment[38]. Purinergic pathway also regulate the function
of NK cells. Proliferation and hypoxia of tumor cells increase the
utilization of ATP and activate cancer-related CD39 and CD73, which
catalyze the continuous dephosphorylation of ATP to AMP and then to
eADO. Extracellular adenosine accumulation interacts with adenosine
receptors expressed on the surface of NK cells and inhibits signaling
through A2aR, so A2aR antibodies are also an important target for tumor
therapy[51]. It has been demonstrated that combined blocking of
TIGIT and A2aR could enhance NK-92 cell-mediated cytotoxicity in
AML[38]. In other tumors, the combination of TIGIT mAb and A2aR mAb
is still being explored[51].