Department of Biochemistry/Cancer Therapy Research Center (CTRC), Theodor-Boveri-Institute, University of Wuerzburg, 97074 Wuerzburg, Germany.
Institute of Veterinary-Anatomy, -Histology and -Embryology, Faculty of Veterinary Medicine, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Viruses. 2020 Jul 12;12(7):750. doi: 10.3390/v12070750.
Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a "Trojan horse" for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.
几种溶瘤病毒（OVs），包括各种人源和犬源腺病毒、犬瘟热病毒、单纯疱疹病毒、呼肠孤病毒以及痘病毒家族的成员，如牛痘病毒和兔粘液瘤病毒，已在临床前和临床环境中成功用于犬类癌症治疗的测试。癌症溶瘤病毒治疗的成功依赖于溶瘤病毒克服宿主免疫系统攻击、优先感染和裂解癌细胞以及引发肿瘤特异性免疫的能力。迄今为止，已经开发了几种不同的策略来克服抗病毒宿主防御障碍。在我们的研究中，我们使用犬脂肪间充质干细胞（cAdMSCs）作为携带溶瘤痘苗病毒哥本哈根株的“特洛伊木马”，以实现对犬软组织肉瘤（CSTS）肿瘤的最大溶瘤作用。单次系统给予携带痘苗病毒的 cAdMSCs 被发现是安全的，并导致 CSTS 异种移植小鼠模型中的肿瘤显著减少和实质性抑制。这是首例证明携带痘苗病毒的 cAdMSCs 可作为 CSTS 肿瘤治疗剂的例子。
