AI Article Synopsis
- Limited treatment options for breast cancer brain metastases (BCBM) highlight the need for new therapies, leading researchers to investigate an engineered oncolytic herpes simplex virus (oHSV) that expresses an anti-CD47 monoclonal antibody.* -
- The combination of this engineered virus (OV-αCD47-G1) with the chemotherapy drug temozolomide (TMZ) showed improved effectiveness in preclinical models, increasing macrophage and NK cell activity against breast tumor cells.* -
- Results indicated that this combination therapy not only enhanced immune response but also significantly extended survival in tumor-bearing mice, suggesting potential benefits for BCBM patients.*
Article Abstract
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-αCD47-G1) that was used to treat both ovarian cancer and glioblastoma. Here, we demonstrate that the combination of OV-αCD47-G1 and temozolomide (TMZ) improve outcomes in preclinical models of BCBM. The combination of TMZ with OV-αCD47-G1 synergistically increased macrophage phagocytosis against breast tumor cells and led to greater activation of NK cell cytotoxicity. In addition, the combination of OV-αCD47-G1 with TMZ significantly prolonged the survival of tumor-bearing mice when compared with TMZ or OV-αCD47-G1 alone. Combination treatment with the mouse counterpart of OV-αCD47-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-αCD47-G1 combined with TMZ should be explored in patients with BCBM.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11260018 | PMC |
| http://dx.doi.org/10.1016/j.omton.2024.200824 | DOI Listing |
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