英國癌癥研究所的科學家們最近在攻克癌癥的征途上前進了一大步,。據(jù)英國廣播公司8月31日報道，他們利用轉(zhuǎn)基因皰疹病毒治療頭頸癌的實驗取得了成功,。
關(guān)于該實驗的報告發(fā)表在近期的《臨床癌癥研究》雜志上,，報告稱，在皇家馬斯登醫(yī)院,，醫(yī)生把這種轉(zhuǎn)基因病毒注入17位淋巴癌患者的體內(nèi),，同時這些參與實驗患者也接受常規(guī)的放療或化療。結(jié)果顯示,，93%的實驗者切除腫瘤后沒有再出現(xiàn)癌腫,。兩年多后，82%的患者沒有出現(xiàn)復發(fā),。13位接受高劑量轉(zhuǎn)基因病毒療法的患者中只有2位病情復發(fā),。目前科研人員實驗的一個重點是，確定針對患者使用的推薦劑量,，同時關(guān)注對癌腫的局部控制和避免擴散,。
這一新的轉(zhuǎn)基因皰疹病毒療法目前也用于皮膚癌患者實驗,。科研人員對這種通常用于制造水痘疫苗的病毒進行了基因改造,，使它只進入癌細胞繁殖,，而不會對健康細胞造成感染。改造后的病毒可具有三重效力：第一,，可以殺死癌細胞,；第二，改造工程使它能產(chǎn)生一種刺激免疫系統(tǒng)的人體蛋白質(zhì),；第三,，它還可以產(chǎn)生一種病毒蛋白質(zhì)，來引誘,、激活人體免疫細胞,，加強患者與癌細胞的對抗機能。
全世界每年約有65萬人被診斷為頭頸癌,，其中有35萬人死于這種不治之癥,。在英國，每年有約8000人罹患頭頸癌,，包括口腔癌、舌癌及喉癌等,。這一研究項目負責人英國癌癥研究所的凱文·哈林頓博士表示，通常接受標準化療和放療的患者約有35%到55%在兩年內(nèi)癌癥復發(fā),，相比之下，新的實驗成果更有希望治愈癌癥,。這種經(jīng)過基因改造的病毒，不會再讓患者染上皰疹,。但他指出,，目前的新療法對發(fā)現(xiàn)較早的I期,、II期癌癥療效良好，但許多患者確診時就已經(jīng)到晚期了,。英國科研人員已決定,，今年將進行首次針對III期癌癥患者的大規(guī)模實驗。
研究人員指出,，目前的實驗尚屬小規(guī)模試驗,，基本上側(cè)重于安全性測試,。要得出新療法比標準放、化療療法效果好的結(jié)論還為時尚早,。英國科學家們已經(jīng)決定,，在今年晚些時候再進行規(guī)模更大的實驗，以將皰疹病毒新療法和目前通用的標準療法效果進行比對,。
英國癌癥研究領域科研信息官員羅斯女士表示,，轉(zhuǎn)基因皰疹病毒療法用于臨床尚需時日，還需要在與常規(guī)療法的比較方面作進一步實驗,。然而,，目前的實驗結(jié)果展示了利用轉(zhuǎn)基因皰疹病毒這一生物學新武器來攻克癌癥的廣闊前景。據(jù)報道,，新療法也有副作用,，通常表現(xiàn)為中輕度，不過,，除了發(fā)燒和疲乏外,，其他大多數(shù)副作用來自化療或放療。(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.
