Cai Hui, Wang Chao, Shukla Sourabh, Steinmetz Nicole F
Department of NanoEngineering/Department of Radiology/Moores Cancer Center/Department of Bioengineering University of California, San Diego La Jolla CA 92093 USA.
Department of Biomedical Engineering Case Western Reserve University 10900 Euclid Avenue Cleveland OH 44106 USA.
Adv Sci (Weinh). 2019 Jun 19;6(16):1802281. doi: 10.1002/advs.201802281. eCollection 2019 Aug 21.
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.
转移性三阴性乳腺癌（TNBC）患者预后较差，因此迫切需要能实现更有效且持久反应的新疗法或药物组合。在此，研发了一种使用豇豆花叶病毒（CPMV）和低剂量环磷酰胺（CPA）的联合疗法，其在体内对4T1小鼠肿瘤具有显著的协同疗效。该联合疗法不仅能抑制原发性肿瘤生长并延长生存期，还能抑制远处肿瘤生长并减少肺转移。机制分析表明，CPMV与CPA的联合可增加多种细胞因子的分泌，激活抗原呈递细胞，增加肿瘤浸润T细胞的丰度，并系统性地逆转免疫抑制。这些结果表明，CPMV原位疫苗接种与化疗相结合可能成为治疗TNBC的一种有效新策略。
