英国癌症研究所的科学家们最近在攻克癌症的征途上前进了一大步。据英国广播公司8月31日报道,他们利用转基因疱疹病毒治疗头颈癌的实验取得了成功。
关于该实验的报告发表在近期的《临床癌症研究》杂志上,报告称,在皇家马斯登医院,医生把这种转基因病毒注入17位淋巴癌患者的体内,同时这些参与实验患者也接受常规的放疗或化疗。结果显示,93%的实验者切除肿瘤后没有再出现癌肿。两年多后,82%的患者没有出现复发。13位接受高剂量转基因病毒疗法的患者中只有2位病情复发。目前科研人员实验的一个重点是,确定针对患者使用的推荐剂量,同时关注对癌肿的局部控制和避免扩散。
这一新的转基因疱疹病毒疗法目前也用于皮肤癌患者实验。科研人员对这种通常用于制造水痘疫苗的病毒进行了基因改造,使它只进入癌细胞繁殖,而不会对健康细胞造成感染。改造后的病毒可具有三重效力:第一,可以杀死癌细胞;第二,改造工程使它能产生一种刺激免疫系统的人体蛋白质;第三,它还可以产生一种病毒蛋白质,来引诱、激活人体免疫细胞,加强患者与癌细胞的对抗机能。
全世界每年约有65万人被诊断为头颈癌,其中有35万人死于这种不治之症。在英国,每年有约8000人罹患头颈癌,包括口腔癌、舌癌及喉癌等。这一研究项目负责人英国癌症研究所的凯文·哈林顿博士表示,通常接受标准化疗和放疗的患者约有35%到55%在两年内癌症复发,相比之下,新的实验成果更有希望治愈癌症。这种经过基因改造的病毒,不会再让患者染上疱疹。但他指出,目前的新疗法对发现较早的I期、II期癌症疗效良好,但许多患者确诊时就已经到晚期了。英国科研人员已决定,今年将进行首次针对III期癌症患者的大规模实验。
研究人员指出,目前的实验尚属小规模试验,基本上侧重于安全性测试。要得出新疗法比标准放、化疗疗法效果好的结论还为时尚早。英国科学家们已经决定,在今年晚些时候再进行规模更大的实验,以将疱疹病毒新疗法和目前通用的标准疗法效果进行比对。
英国癌症研究领域科研信息官员罗斯女士表示,转基因疱疹病毒疗法用于临床尚需时日,还需要在与常规疗法的比较方面作进一步实验。然而,目前的实验结果展示了利用转基因疱疹病毒这一生物学新武器来攻克癌症的广阔前景。据报道,新疗法也有副作用,通常表现为中轻度,不过,除了发烧和疲乏外,其他大多数副作用来自化疗或放疗。(生物谷 Bioon.com)
doi:10.1158/1078-0432.CCR-10-0196
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PMID:
Phase I/II Study of Oncolytic HSVGM-CSF in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck
Kevin J. Harrington, Mohan Hingorani, Mary Anne Tanay, Jennifer Hickey, Shreerang A. Bhide, Peter M. Clarke, Louise C. Renouf, Khin Thway, Amen Sibtain, Iain A. McNeish, Kate L. Newbold, Howard Goldsweig, Robert Coffin, and Christopher M. Nutting
Purpose: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN). Experimental Design: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43) and dose-escalating (106, 106, 106, 106 pfu/mL for cohort 1; 106, 107, 107, 107 for cohort 2; 106, 108, 108, 108 for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored. Results: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months). Conclusions: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 106, 108, 108, 108. Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN. Clin Cancer Res; 16(15); 4005–15. ©2010 AACR.