Open AccessCowpea Mosaic Virus Immunotherapy Combined with Cyclophosphamide Reduces Breast Cancer Tumor Burden and Inhibits Lung Metastasis
Author(s) -
Cai Hui,
Wang Chao,
Shukla Sourabh,
Steinmetz Nicole F.
Publication year - 2019
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201802281
Subject(s) - medicine , cyclophosphamide , metastasis , immunotherapy , combination therapy , cancer research , cowpea mosaic virus , in vivo , immunosuppression , chemotherapy , cancer , breast cancer , primary tumor , triple negative breast cancer , oncology , immunology , virus , biology , plant virus , microbiology and biotechnology
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.