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What Lies Within: Novel Strategies in Immunotherapy for Non-Small Cell Lung Cancer

机译:内容所在:非小细胞肺癌免疫治疗的新策略

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Introduction. Immunotherapy has become an increasingly important therapeutic strategy for those with cancer, with phase III studies demonstrating survival advantages in melanoma and castration-resistant prostate cancer. Non-small cell lung cancer (NSCLC) is a promising target for the next generation of immune-based strategies. In this article, we examine the current state of the art in lung cancer immunotherapy, including vaccines that specifically target lung tumor antigens and immune checkpoint antibodies such as antiprogrammed death 1 (anti-PD-1). Both approaches harness innate immunity against tumors by suppressing tumor-induced immune paresis. Methods. To identify relevant clinical trials of immunotherapy in NSCLC, PubMed and Medline databases were searched using the terms a??immunotherapya?? and a??NSCLC,a?? and several other therapy-specific search terms (e.g., PD-1, NSCLC). Additionally, abstracts presented at international lung cancer symposia, the American Society of Clinical Oncology annual meeting, and the European Society of Medical Oncology annual meeting between 2005 and 2013 were evaluated. Results. Large international phase III trials of NSCLC vaccines have completed accrual in both the adjuvant and metastatic disease settings. Results of the START study were disappointing, but results from other studies are still awaited. Immune checkpoint modulation has shown promise, with separate phase I studies of the anti-PD-1 antibody, nivolumab, and anti-PD-L1 antibody, MPDL3280A, demonstrating good tolerance and durable responses for certain patients with NSCLC who were heavily pretreated. Conclusions. Immune-based strategies have shown initial promise for early- and advanced-stage NSCLC. Validating these findings in randomized studies and discovering durable biomarkers of response represent the next challenges for investigation.
机译:介绍。免疫疗法已成为对癌症患者越来越重要的治疗策略,III期研究证明了黑色素瘤和去势抵抗性前列腺癌的生存优势。非小细胞肺癌(NSCLC)是下一代基于免疫的策略的有希望的靶标。在本文中,我们研究了肺癌免疫治疗的最新技术,包括专门针对肺肿瘤抗原和免疫检查点抗体(例如抗程序性死亡1(anti-PD-1))的疫苗。两种方法都通过抑制肿瘤诱导的免疫轻瘫来利用对肿瘤的先天免疫。方法。为了确定NSCLC中免疫疗法的相关临床试验,使用术语“免疫疗法”搜索了PubMed和Medline数据库。还有一个?NSCLC,一个?以及其他几个特定于治疗的搜索字词(例如PD-1,NSCLC)。此外,还评估了在2005年至2013年之间的国际肺癌研讨会,美国临床肿瘤学会年会和欧洲医学肿瘤学会年会上提交的摘要。结果。 NSCLC疫苗的大型国际III期试验已经在佐剂和转移性疾病背景下完成了应计项目。 START研究的结果令人失望,但仍在等待其他研究的结果。免疫检查点调节已显示出希望,针对抗PD-1抗体nivolumab和抗PD-L1抗体MPDL3280A进行了单独的I期研究,证明了对某些经过大量预处理的NSCLC患者具有良好的耐受性和持久反应。结论。基于免疫的策略已显示出早期和晚期NSCLC的初步前景。在随机研究中验证这些发现并发现持久的反应生物标志物是研究的下一个挑战。

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