Enhanced treatment of breast cancer brain metastases with oncolytic virus expressing anti-CD47 antibody and temozolomide

Jing Wang; Lei Tian; Tasha Barr; Lewei Jin; Yuqing Chen; Zhiyao Li; Ge Wang; Jian-Chang Liu; Li-Shu Wang; Jianying Zhang; David Hsu; Mingye Feng; Michael A Caligiuri; Jianhua Yu

doi:10.1016/j.omton.2024.200824

Enhanced treatment of breast cancer brain metastases with oncolytic virus expressing anti-CD47 antibody and temozolomide

Mol Ther Oncol. 2024 Jun 5;32(3):200824. doi: 10.1016/j.omton.2024.200824. eCollection 2024 Sep 19.

Authors

Jing Wang^{1

2

3}, Lei Tian^{1

2}, Tasha Barr^{1

2}, Lewei Jin^{1

2}, Yuqing Chen^{1

2}, Zhiyao Li^{1

2}, Ge Wang^{1

2}, Jian-Chang Liu⁴, Li-Shu Wang¹, Jianying Zhang⁵, David Hsu⁴, Mingye Feng⁶, Michael A Caligiuri^{1

2

7}, Jianhua Yu^{1

2

6

7}

Affiliations

¹ Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
² Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
³ Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ Center for Biomedicine and Genetics, Beckman Research Institute of City of Hope, Los Angeles, CA 91010, USA.
⁵ Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
⁶ Department of Immuno-Oncology, City of Hope, Los Angeles, CA 91010, USA.
⁷ City of Hope Comprehensive Cancer Center, Los Angeles, CA 91010, USA.

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.

Keywords: CD47; TMZ; anti-CD47 antibody; breast cancer brain metastases; don't eat me signal; oncolytic herpes simplex virus; temozolomide; tumor microenvironment.

Abstract

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