美国科学家对痘苗病毒进行了基因改良，以此作为治疗的手段，取得了良好的治疗癌症效果。这一研究发表在近期出版的美国《临床研究杂志》上。
这项研究由宾夕法尼亚匹兹堡大学病毒学家斯蒂芬·索恩尼领导。研究人员首先从痘苗病毒中剔除了两个基因，这两个基因对于病毒在正常细胞中的生长是必要的；然后移接了一段基因，使痘苗病毒能制造粒细胞-巨噬细胞集落刺激因子，刺激机体的免疫系统，识别并攻击被病毒感染了的肿瘤。
研究人员利用肝脏癌瘤已经传播到肺部的兔子进行试验，将上述改造好的工程病毒注入野兔体内，发现肝脏和肺部的肿瘤都变小了，而没有接受注射的兔子，肝脏肿瘤扩大了4倍，肺部肿瘤也变得明显。索恩尼表示，如果加大注射剂量，或用病毒疗法再辅以其它医疗方法，我们很可能会攻克癌症。
索恩尼表示，他们正在和美国食品药品监督管理局磋商，计划明年初将这种病毒疗法在患固体肿瘤的癌症病人身上进行人体试验。他认为，人体组织研究显示，病毒不会感染正常细胞，但在治疗中，仍需要一些安全措施，如注射疫苗免疫球蛋白，以预防及少见的对疫苗的不良反应。
10多年来，科学家一直在改造病毒，使它们能有选择地感染、破坏癌细胞，但收效甚微。至今最先进的肿瘤增殖腺病毒ONYX-015是一种改造的腺病毒，中国已于2005年用它治疗头颈癌。宾夕法尼亚费城福克斯?蔡斯癌症中心的医疗肿瘤学家路易斯·维纳说，痘苗病毒可能比ONYX-015更加先进，它的抗肿瘤效果更强，但我们仍需谨慎对待，因为这些只经过了动物试验，用在人体上效果可能不太理想。（生物谷Bioon.com）
生物谷推荐原始出处：
Clinical Cancer Research 15, 1730, March 1, 2009.doi: 10.1158/1078-0432.CCR-08-2008
Oncolytic Adenoviral Mutants with E1B19K Gene Deletions Enhance Gemcitabine-induced Apoptosis in Pancreatic Carcinoma Cells and Anti-Tumor Efficacy In vivo
Stephan Leitner1, Katrina Sweeney1, Daniel ?berg1, Derek Davies2, Enrique Miranda1, Nick R. Lemoine1 and Gunnel Halldén1
Authors' Affiliations: 1 Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, and 2 FACS Laboratory, London Research Institute, Cancer Research UK, Lincolns Inn Fields, London, United Kingdom
Requests for reprints: Gunnel Halldén, Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
Purpose: Pancreatic adenocarcinoma is a rapidly progressive malignancy that is highly resistant to current chemotherapeutic modalities and almost uniformly fatal. We show that a novel targeting strategy combining oncolytic adenoviral mutants with the standard cytotoxic treatment, gemcitabine, can markedly improve the anticancer potency.
Experimental Design: Adenoviral mutants with the E1B19K gene deleted with and without E3B gene expression (AdE1B19K and dl337 mutants, respectively) were assessed for synergistic interactions in combination with gemcitabine. Cell viability, mechanism of cell death, and antitumor efficacy in vivo were determined in the pancreatic carcinoma cells PT45 and Suit2, normal human bronchial epithelial cells, and in PT45 xenografts.
Results: The E1B19K-deleted mutants synergized with gemcitabine to selectively kill cultured pancreatic cancer cells and xenografts in vivo with no effect in normal cells. The corresponding wild-type virus (Ad5) stimulated drug-induced cell killing to a lesser degree. Gemcitabine blocked replication of all viruses despite the enhanced cell killing activity due to gemcitabine-induced delay in G1/S-cell cycle progression, with repression of cyclin E and cdc25A, which was not abrogated by viral E1A-expression. Synergistic cell death occurred through enhancement of gemcitabine-induced apoptosis in the presence of both AdE1B19K and dl337 mutants, shown by increased cell membrane fragmentation, caspase-3 activation, and mitochondrial dysfunction.
Conclusions: Our data suggest that oncolytic mutants lacking the antiapoptotic E1B19K gene can improve efficacy of DNA-damaging drugs such as gemcitabine through convergence on cellular apoptosis pathways. These findings imply that less toxic doses than currently practiced in the clinic could efficiently target pancreatic adenocarcinomas when combined with adenoviral mutants.
