CELL INTELLIGENCE · 肿瘤细胞治疗研究

Limited therapeutic options are available for patients with breast cancer brain metastases (BCBM), and thus there is an urgent need for novel treatment approaches. We previously engineered an effective oncolytic herpes simplex virus 1 (oHSV) expressing a full-length anti-CD47 monoclonal antibody (mAb) with a human IgG1 scaffold (OV- CD47-G1) that was used to treat both ovarian cancer and glioblastoma. Here, we demonstrate that the combination of OV- CD47-G1 and temozolomide (TMZ) improve outcomes in preclinical models of BCBM. The combination of TMZ with OV- CD47-G1 synergistically increased macrophage phagocytosis against breast tumor cells and led to greater activation of NK cell cytotoxicity. In addition, the combination of OV- CD47-G1 with TMZ significantly prolonged the survival of tumor-bearing mice when compared with TMZ or OV- CD47-G1 alone. Combination treatment with the mouse counterpart of OV- CD47-G1, termed OV-A4-IgG2b, also enhanced mouse macrophage phagocytosis, NK cell cytotoxicity, and survival in an immunocompetent model of mice bearing BCBM compared with TMZ or OV-A4-IgG2b alone. Collectively, these results suggest that OV- CD47-G1 combined with TMZ should be explored in patients with BCBM.