Centre for Molecular Oncology & Imaging, Institute of Cancer, Barts and the London School of Medicine and Dentistry, London, UK.
Gene Ther. 2009 Oct;16(10):1223-33. doi: 10.1038/gt.2009.74. Epub 2009 Jul 9.
Survival after pancreatic cancer remains poor despite incremental advances in surgical and adjuvant therapy, and new strategies for treatment are needed. Oncolytic virotherapy is an attractive approach for cancer treatment. In this study, we have evaluated the effectiveness of the Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of vaccinia virus was effective against all human pancreatic carcinoma cells tested in vitro, especially those insensitive to oncolytic adenovirus. The virus displayed inherently high selectivity for cancer cells, sparing normal cells both in vitro and in vivo, with effective infection of tumors after both intravenous (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin-angiostatin fusion protein was confirmed in a pancreatic cancer model both in vitro and in vivo, with evidence of inhibition of angiogenesis. This novel vaccinia virus showed significant antitumor potency in vivo against the Suit-2 model by i.t. administration. This study suggests that the novel Lister strain of vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential therapeutic agent for pancreatic cancer.
尽管在手术和辅助治疗方面取得了渐进式的进展，但胰腺癌的生存率仍然很差，需要新的治疗策略。溶瘤病毒治疗是癌症治疗的一种有吸引力的方法。在这项研究中，我们评估了携带内皮抑素-血管生成素融合基因的李斯特疫苗株痘苗病毒（VVhEA）作为治疗胰腺癌的新方法的有效性。李斯特疫苗株痘苗病毒对体外测试的所有人类胰腺癌细胞均有效，特别是对溶瘤腺病毒不敏感的细胞。该病毒对癌细胞具有内在的高选择性，在体外和体内均能保护正常细胞，静脉（i.v.）和肿瘤内（i.t.）给药后均可有效感染肿瘤。在体外和体内的胰腺癌模型中均证实了内皮抑素-血管生成素融合蛋白的表达，并证实了血管生成的抑制。通过肿瘤内给药，新型痘苗病毒在 Suit-2 模型中显示出显著的体内抗肿瘤活性。这项研究表明，携带内皮抑素-血管生成素融合基因的新型李斯特株痘苗病毒是一种治疗胰腺癌的潜在治疗剂。
