JRO:“自杀式基因疗法”杀死前列腺癌细胞

2015-12-16 绿谷生物 ibioo.Com
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来自美国休斯顿卫理公会医院的研究人员进行了一项长期临床研究,研究结果表明放射治疗结合"自杀基因治疗"技术可以为前列腺癌病人提供安全有效的治疗。"自杀式基因治疗"技术通过对前列腺癌细胞进行基因修饰使得癌细胞向病人免疫系统发送信号实现"自杀"过程。相关研究结果发表在国际学术期刊Journal of Radiation Oncology上。
 
共有66名前列腺癌病人参与了1999年到2003年间的II期临床研究,研究人员将参与者分为两组,其中一组病人的肿瘤细胞只存在于前列腺组织,研究人员将该组命名为Arm A,这些病人只接受放射治疗,而另外一组病人携带更具侵袭性的前列腺癌细胞,研究人员将该组命名为Arm B,这组病人要同时接受放射治疗和激素治疗。Arm A组内的病人在研究过程中接受了两次试验性基因治疗,而Arm B组的病人接受了三次基因治疗。
 
文章作者E. Brian Butler说道:"我们使用腺病毒携带能够产生胸苷激酶(TK)的疱疹病毒基因,直接靶向到肿瘤细胞,一旦基因完成导入就会开始合成TK,在此之后,我们给病人服用一种常用的抗疱疹药物--伐昔洛韦,这样就能够攻击疱疹病毒DNA,使合成TK的肿瘤细胞发生自我摧毁,所以我们把这项技术称作'自杀式基因疗法'。"
 
Butler表示,一旦伐昔洛韦开始攻击肿瘤细胞,它就会唤起病人的免疫系统,对癌细胞发起总攻。
 
根据这项研究的结果,将基因疗法与放射治疗结合使用,无论是否进行激素治疗,都非常具有应用前景。两组内完成临床试验的62名病人五年生存率都非常高,并且根据生化检测结果没有发现复发迹象。
 
除此之外,使用联合治疗方法的病人各项参数均好于单独使用放射治疗的病人,研究人员表示,大部分参与研究的病人基本没有出现副作用,目前III期临床试验正在进行,在得到FDA批准之前仍然需要对该方法的安全性和有效性进行进一步评估。
 
 
 
Long-term outcome of a phase II trial using immunomodulatory in situ gene therapy in combination with intensity-modulated radiotherapy with or without hormonal therapy in the treatment of prostate cancer
 
Bin S. Teh, Hiromichi Ishiyama, Wei-Yuan Mai, Timothy C. Thompson, E. Brian Butler
 
Objective
 
The objective of this study is to report the long-term outcome of a phase II trial of immune-modulatory in situ gene therapy (GT) in combination with intensity-modulated radiotherapy (IMRT) with or without hormonal therapy for the treatment of prostate cancer.
 
Methods
 
GT was comprised of intraprostatic injection of adenoviral vector containing herpes simplex thymidine kinase (ADV/HSV-tk) followed by valacyclovir. A mean dose of 76 Gy was delivered to the prostate with IMRT. Low-risk patients (arm A; T1-T2a, Gleason score <7, pretreatment PSA <10) were treated with two injections of ADV/HSV-tk, each followed by valacyclovir, and IMRT. Intermediate/high-risk patients (arm B; T2b-T3, Gleason score ≥7, pretreatment PSA ≥10) were treated with three injections of ADV/HSV-tk, each followed by valacyclovir, IMRT, and hormonal therapy.
 
Results
 
Sixty-six patients (33 patients in each arm) were enrolled. The median follow-up was 100 months. Five-year freedom from failure (FFF) rates were 94 and 91 % for arms A and B, respectively. Five-year overall survival (OS) rates were 97 and 94 % for arms A and B. Negative biopsy rates at 24 months were 83 and 79 % for arms A and B. One patient in arm B developed grade 3 elevation in liver enzyme. There was no grade 3 or higher hematologic toxicity. One patient had grade 3 genitourinary toxicity. There was no grade 3 or higher lower gastrointestinal toxicity.
 
Conclusion
 
The combination of immunomodulatory in situ gene therapy and IMRT with or without hormonal therapy is feasible, safe, and effective in the treatment of prostate cancer. The effectiveness of this combined approach was likely through enhanced cytotoxicity, antitumor immune response, and abscopal effects. This approach with long term follow up appears to provide better clinical outcome over historical controls. A randomized trial of this strategy is currently ongoing.