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].