In combination with conventional therapies (e.g., targeted therapy, chemotherapy, and angiogenesis inhibitors etc.), immunotherapies targeting checkpoint molecules have shown promise in the treatment of solid or liquid tumors. However, apoptotic regulatory T cells (Treg) induced by such therapies often become more suppressive in the tumor microenvironment (TME), through increased generation of adenosine tightly controlled by ectonucleotidases, viz. CD39 and CD73. CD39/ENTPD1, a novel checkpoint molecule, is highly expressed and activated on the tumor vasculature and infiltrating immune cells, promoting tumor growth. Deletion or blockade of CD39 enhances anti-tumor activity by augmenting anti-tumor immune responses and inhibiting tumor angiogenesis. The present invention is based at least in part on the development of anti-CD39 antibodies which mediate CD39 downregulation on immune cells, such as T-cells with markers of T-cell exhaustion, and the demonstrated utility of these antibodies in blocking tumor growth with minimal side effects in pre-clinical models.與習知療法(例如靶向療法、化學療法及血管生成抑制劑等)組合，靶向檢查點分子之免疫療法已展示在實體或液體腫瘤治療中之前景。然而，由此類療法誘導之凋亡性調控T細胞(Treg)在腫瘤微環境(TME)中通過受外核苷酸酶，亦即CD39及CD73嚴密控制之腺苷的產生增加而常常變為更抑制性的。新穎檢查點分子CD39/ENTPD1在腫瘤脈管系統及浸潤免疫細胞上高度表現及活化，從而促進腫瘤生長。CD39之缺失或阻斷藉由加強抗腫瘤免疫反應及抑制腫瘤血管生成而增強抗腫瘤活性。本發明至少部分係基於介導具有T細胞耗竭標記物之諸如T細胞之免疫細胞上的CD39下調之抗CD39抗體之研發，及此等抗體在臨床前模型中所展現之以最小副作用阻斷腫瘤生長的效用。
