Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Mol Ther. 2010 Apr;18(4):692-9. doi: 10.1038/mt.2009.318. Epub 2010 Jan 19.
Cancer therapy using oncolytic viruses represents a promising new approach for controlling ovarian cancer. In this study, we have circumvented the limitation of repeated vaccination by employing different virus vectors, Semliki Forest Virus (SFV) and vaccinia virus (VV) for boosting the immune response. We found that infection of tumor-bearing mice with VV followed by infection with SFV or vice versa leads to enhanced antitumor effects against murine ovarian surface epithelial carcinoma (MOSEC) tumors. Furthermore, infection with VV-ovalbumin (OVA) followed by infection with SFV-OVA or vice versa was found to lead to enhanced OVA-specific CD8(+) T-cell immune responses. In addition, we found that infection with SFV-OVA followed by infection with VV-OVA leads to enhanced antitumor effects in vivo and enhanced tumor killing in vitro through a combination of viral oncolysis and antigen-specific immunity. The clinical implications of this study are discussed.
溶瘤病毒在癌症治疗中的应用为控制卵巢癌提供了一种很有前途的新方法。在这项研究中,我们通过使用不同的病毒载体(辛德毕斯森林病毒(SFV)和痘苗病毒(VV))来增强免疫反应,克服了重复接种的限制。我们发现,用 VV 感染荷瘤小鼠,然后用 SFV 或反之亦然,可增强对小鼠卵巢表面上皮癌(MOSEC)肿瘤的抗肿瘤作用。此外,我们发现,用 VV-卵清蛋白(OVA)感染,然后用 SFV-OVA 或反之亦然感染,可导致增强的 OVA 特异性 CD8+T 细胞免疫反应。此外,我们发现,用 SFV-OVA 感染,然后用 VV-OVA 感染,可通过溶瘤病毒和抗原特异性免疫的联合作用,在体内增强抗肿瘤作用,并在体外增强肿瘤杀伤作用。讨论了这项研究的临床意义。