Cowpea Mosaic Virus Immunotherapy Combined with Cyclophosphamide Reduces Breast Cancer Tumor Burden and Inhibits Lung Metastasis

Patients with metastatic triple‐negative breast cancer (TNBC) have a poor prognosis, so new therapies or drug combinations that achieve more effective and durable responses are urgently needed. Here, a combination therapy using cowpea mosaic virus (CPMV) and low doses of cyclophosphamide (CPA) is de...

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Published inAdvanced science Vol. 6; no. 16; pp. 1802281 - n/a
Main Authors Cai, Hui, Wang, Chao, Shukla, Sourabh, Steinmetz, Nicole F.
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 21.08.2019
John Wiley and Sons Inc
Wiley
Subjects
Antigens
Breast cancer
cancer immunotherapy
Cancer therapies
Chemotherapy
Drug dosages
Ethanol
Immune system
Immunotherapy
in situ vaccination
Medical prognosis
Metastasis
Mortality
Software
Statistical analysis
triple‐negative breast cancer
Tumors
Variance analysis
Viruses
in situ vaccination
triple‐negative breast cancer
chemotherapy
cancer immunotherapy
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Summary:Patients with metastatic triple‐negative breast cancer (TNBC) have a poor prognosis, so new therapies or drug combinations that achieve more effective and durable responses are urgently needed. Here, a combination therapy using cowpea mosaic virus (CPMV) and low doses of cyclophosphamide (CPA) is developed with remarkable synergistic efficacy against 4T1 mouse tumors in vivo. The combination therapy not only attenuates the growth of primary tumor and increases survival, but also suppresses distant tumor growth and reduces lung metastasis. Mechanistic analysis indicates that the combination of CPMV and CPA increases the secretion of several cytokines, activates antigen‐presenting cells, increases the abundance of tumor infiltrating T cells, and systematically reverses the immunosuppression. These results show that the combination of CPMV in situ vaccination with chemotherapy may become a potent new strategy for the treatment of TNBC. A combination therapy is developed to treat metastatic triple‐negative breast cancer by combining cowpea mosaic virus in situ vaccination and chemo‐induced immunogenic cell death. The combination therapy induces systematic antitumor immunity with synergistic efficacy against both the treated and nontreated tumor, and can also reduce the lung metastasis.
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ISSN:2198-3844
2198-3844
DOI:10.1002/advs.201802281