3.2CD39 mAb combined with CTLA-4 mAb
CTLA-4 is a molecule belonging to the immunoglobulin superfamily first discovered in cDNA libraries of CTLs and expressed in activated T cells, Tregs, and acute myeloid leukemia cells[24, 29].Although CTLA-4 and its homologue CD28 bind to the ligand B7 on B cells and APCs, stimulation of CTLA-4 does not result in T cell activation, but rather to T-cell-mediated antibodies that inhibit and prevent allograft rejection[19, 21].Blocking the CTLA-4-B7 interaction with an anti-CTLA-4 mAb results in an enhanced alloantigen response that inhibits negative signaling to T cells[28].However, anti-CTLA-4 is rarely effective as a single drug in highly oncogenic and immunogenic tumors. Targeting of CD39 with POM-1 has synergistic effect with anti-CTLA-4 checkpoint blocking. Specifically blocking CD39 with POM-1 significantly increased the antitumor activation of CTLA-4 mAb in a mouse model of lung metastasis, and showed better efficacy in a CD39-deficient mouse model of tumor transplanted with B16F10[35]. Recent research also shows that the expression of CTLA-4 and CD39 may be potential target molecules that inhibit Treg activity in situ[36]. Although there is a little literature on the combination of CD39 mAb with CTLA-4 mAb, according to the current study, the combination of the two mAb has great potential in tumor therapy, especially in the treatment of tumor metastasis.