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据在瑞士日内瓦举办的2016欧洲肺癌大会（ELCC）上公布的一项Ib期研究结果，活菌免疫治疗联合化疗可使性胸膜间皮瘤（MPM）患者产生90%以上的疾病控制率，59%的缓解率。
美国加州大学旧金山分校Helen Diller家庭综合癌症中心的医学教授Thierry Jahan说道：“恶性胸膜间皮瘤是肺内层癌症，很罕见且难于治疗。培美曲塞和铂类的标准治疗可达到30%的缓解率，但是对生存影响较小。因此这类人群具有显然未被满足的需求。”
MPM患者在肿瘤中强烈表达间皮素抗原。CRS-207是一种活的，衰减单核细胞李斯特菌，包含两个基因缺失，可以减少致病性，也可以被设计来表达间皮素。
Jahan表示：“在我们的早期研究中，CRS-207在间皮素表达肿瘤患者中诱导了一种抗间皮素应答和细胞肿瘤特异性免疫。我们也有数据表明，这种免疫治疗与化疗协同作用，因此检测这种免疫靶向药物联合化疗的效应是自然的事情。”
目前的研究测定了CRS-207联合标准化疗对于晚期不可切除间皮瘤患者的疗效。有38例患者间隔两周接受两次CRS-207注射，间隔三周注射培美曲塞加顺铂，总共6个周期，接着间隔三周注射另两次CRS-207。合适的患者每8周接受维持CRS-207治疗。每8周进行随访，直至疾病进展。
在中位随访9.4个月（范围：0.2-28.1个月）后，研究人员发现59%的患者产生部分缓解，35%的患者疾病稳定，总疾病控制率为94%。中位无进展生存为8.5个月，Jahan表示：“接受CRS-207联合化疗的患者具有深度缓解，90%以上的疾病控制。”
与CRS-207相关的主要不良反应为温度尖峰和寒战。这与输液和24小时内的分解有关。
Jahan 表示：“我们看到，良好的免疫活性确认了利用该药的临床前假设。它似乎激活了先天性免疫和适应性免疫，然后与化疗发展协同效应。”他总结说：“CRS-207对间皮瘤患者来说，是一种令人振奋的药物。我们的初步结果鼓舞人心，表明当将该药加入到标准化疗中，临床活性增强了。支持随机试验对CRS-207作用的进一步评估，该研究目前处在计划阶段。”
瑞士苏黎世大学医院肿瘤学教授Rolf Stahel对此评论表示：“这些结果表明，加入这种免疫治疗与化疗相比，可提高缓解率，提供更长的无进展生存。这支持了这种疫苗能够获益的假设，这将在临床试验中得到验证。”
文献
1) 208O_PR: CRS-207 with chemotherapy (chemo) in malignant pleural mesothelioma (MPM): Results from a phase 1b trial. T. Jahan, US. Thursday 14th April 2016 – 17:45-18:00 Multidisciplinary management of thoracic malignancies Room A
摘要原文（208O_PR）
CRS-207 with chemotherapy (chemo) in malignant pleural mesothelioma (MPM): Results from a phase 1b trial
T. Jahan1, R. Hassan2, E. Alley3, H. Kindler4, S. Antonia5, C. Whiting6, L. Coussens7, A.L. Murphy6, A. Thomas2, D.G. Brockstedt6
Background: MPM is an aggressive disease with poor prognosis. CRS-207 is live, attenuated, double-deleted Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin, activating innate and adaptive immunity. The combination of CRS-207 and chemo may act synergistically to alter the tumor microenvironment to potentiate immune-mediated killing.
Methods: Eligible patients (pts) were chemo-naïve with unresectable MPM, ECOG 0-1, and adequate organ function. Patients received 2 CRS-207 infusions (1×109 CFU) 2 weeks apart, 6 cycles of pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) 3 weeks apart, followed by 2 additional CRS-207 infusions 3 weeks apart. Eligible patients received maintenance CRS-207 every 8 weeks; all patients were followed every 8 weeks until disease progression.. Study objectives include safety, immunogenicity, tumor response and tumor marker kinetics. Immune analyses included multiplexed immunohistochemistry (IHC) of tumor-infiltrating lymphocytes (TILs), flow cytometry analysis of peripheral blood mononuclear cells, and Luminex analysis of serum biomarkers.
Results: As of August 2015, 38 pts have been enrolled. The most commonly reported CRS-207-related adverse events include grades 1/2 infusion-related fever, chills/rigors, hypotension and nausea/vomiting with no treatment-related serious adverse events or deaths. Of evaluable pts, 59% (20/34) had partial response post-treatment and 35% (12/34) had stable disease for overall 94% disease control rate. Median progression-free survival (PFS) was 8.5 months (mos); median overall survival had not been reached. IHC data from 3 patients revealed an increase in TILs post-CRS-207. Treatment-associated changes in circulating immune cells and biomarkers were also observed.
Conclusions: CRS-207 has been well tolerated and in combination with chemo showed encouraging anti-tumor activity with 59% response rate and median PFS of 8.5 mos. Recruitment and expansion of TILs and changes in circulating immune cells and serum biomarkers were observed post-CRS-207. These results appear considerably better than those expected with chemo alone and will be evaluated in a Phase 3 trial.
