[转移贴]科学家研制出新型肺癌疫苗

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原贴由论坛会员503814发表于 2011-10-25 21:08 |

英国《柳叶刀—肿瘤学》杂志日前刊登报告说，一种肺癌疫苗在人类临床试验中显出初步成效，将它与化学疗法联合使用可以更好地控制癌症病情。

本次试验由法国斯特拉斯堡大学等机构研究人员完成，共涉及148名已经到癌症后期的非小细胞肺癌患者。非小细胞肺癌是肺癌的一种，癌症后期通常采用化学疗法进行治疗。在本次试验中，一半患者采用常规化学疗法，另一半患者在接受化疗的同时还注射这种名为TG4010的疫苗。

结果显示，注射疫苗的患者病情得到了更好控制，有43%的患者在6个月后癌症没有进一步发展，而只采取化学疗法的患者中这一比例为35%。

据介绍，这种疫苗通过人体免疫系统发挥作用，它能够“训练”免疫系统辨识一些特殊的蛋白质。如果肺部细胞发生癌变，细胞表面的蛋白质会发生相应变化，经过“训练”的免疫系统就可以凭此辨别出癌变细胞，对其发起攻击，控制病情发展。

研究人员说，虽然疫苗显示出初步成效，但效果并不特别显著，接下来将继续研究，争取能让疫苗发挥更大的治疗作用。

The Lancet Oncology, Early Online Publication, 22 October 2011

Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial

Prof Elisabeth Quoix MD a , Prof Rodryg Ramlau MD b, Prof Virginie Westeel MD c, Zsolt Papai MD d, Anne Madroszyk MD e, Alain Riviere MD f, Piotr Koralewski MD g, Jean-Luc Breton MD h, Erich Stoelben MD i, Denis Braun MD j, Didier Debieuvre MD k, Hervé Lena MD l, Marc Buyse ScD m, Prof Marie-Pierre Chenard MD n, Bruce Acres PhD o, Gisèle Lacoste MD o, Bérangère Bastien MSc o, Annette Tavernaro MSc o, Nadine Bizouarne PhD o, Jean-Yves Bonnefoy PhD o, Jean-Marc Limacher MD o

[Summary]
Background
Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC.

Methods
148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (108 plaque forming units) plus cisplatin (75 mg/m2 on day 1) and gemcitabine (1250 mg/m2 on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818.

Findings
6-month PFS was 43·2% (32 of 74; 95% CI 33·4—53·5) in the TG4010 plus chemotherapy group, and 35·1% (26 of 74; 25·9—45·3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23·3%) versus six of 72 (8·3%), 12 (16·4%) versus two (2·8%), and four (5·5%) versus zero (0%), respectively. The most common grade 3—4 adverse events were neutropenia (33 [45·2%] of patients in the TG4010 plus chemotherapy group vs 31 [43·1%] in the chemotherapy alone group) and fatigue (18 [24·7%] vs 13 [18·1%]); the only grade 3—4 events that differed significantly between groups were anorexia (three [4·1%] vs 10 [13·9%]) and pleural effusion (none vs four [5·6%]). 38 of 73 patients (52·1%) in the TG4010 plus chemotherapy group and 34 of 72 (47·2%) in the chemotherapy alone group had at least one serious adverse event.

Interpretation
This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B—3 trial has been initiated.

Funding
Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.