4.1CD73 mAb combined with PD-1/PD-L1 mAb
As is mentioned above, CD73-derived adenosine strongly mediates tumor
immune status and metastasis, and weak patient response to PD-1
antibodies may also be associated with elevated intratomatous adenosine
levels. In this context, the combination of CD73 mAb and PD-1 mAb may be
particularly effective in the immunotherapy of tumors. Currently,
various studies are focusing on the clinical effect of combining
treatment of CD73 inhibition with PD-1 blockade. In melanoma, breast
cancer, colon cancer, non-small cell lung cancer (NSCLC), prostate
cancer and other malignant tumors[20, 39, 41], Combining CD73 mAb
with PD-1 mAb has shown a more significant effect than these drugs
alone. The high expression of CD73 on the surface of tumor cells shows a
weaker effect of immunotherapy with PD-1 antibody, and the combined use
of PD-1 mAb and CD73 mAb prominently inhibited tumor
growth[42],increased gene expression related to inflammation and T
cell function, causing an increase in the number and activity of
tumor-infiltrating CD8+T cells and the production of IFN-γ and TNF-α of
them[16, 42].It is also reported that MEDI9447, when combined with
anti-PD-1 antibodies, can produce a better antitumor effect, which is
supported by multiple phase I/II trials based on MEDI9447. Preliminary
phase I data for MEDI9447(NCT02503774) have recently been
reported[20].The safety of MEDI9447 and duvacizumAb (anti-PD-L1)
treatment is controllable, and PD-1 is consistent with its mechanism of
function. BMS-986179 was also found to enhance the antineoplastic
activity of anti-PD-1mAb in preclinical animal models[15,
67].Interestingly, the combination of A2AR antagonist and PD-1
antibody also showed an anti-metastasis effect. However, the combination
therapy with A2AR antagonists was effective only when tumors expressed
high CD73 levels, suggesting that CD73 can also be used as a potential
tumor indicator to assess patients’ benefit from combination therapy and
prognosis[12, 15, 40].