With its measurable impact on patient survival, there’s no denying that immunotherapy is already causing momentum in ways that cancer is treated. Drug researchers and developers are identifying new candidates in their growing pipelines and exploring combinations of immunotherapies, while regulatory agencies are providing expedited review and approval of these therapies for new indications at an unprecedented rate.
来自Ipilimumab的检查点抑制剂（Yervoy®) to nivolumab (Opdivo®）到Pembrozumab（Keytruda®) to the most recently approved atezolizumab (TecentriqTM），每个突破都提供了对如何激活和操纵的免疫系统如何激活和操纵来对抗各种癌症的新见解。
新发布的研究
Ongoing research strives to understand the longer-term potential of these therapies. For example, pembrolizumab, which may be prescribed when the disease relapses or fails to respond to ipilimumab, has recently shown to outperform ipilimumab as a first-line therapy. A third of patients treated with pembrolizumab showed an overall response when treated for melanoma; 73% of those responders had an ongoing response lasting as least two years.
响应持续时间范围从>1.3到>38.8个月，表明这些患者的免疫系统保留了其抗癌能力，并提供了持久的反应。此外，在一个单独的直接比较中，作为一线单药治疗的伊匹利单抗，使用pembrolizumab的转移性黑色素瘤患者的2年总生存率从43%增加到55%。
BMS also released the results of its two-year overall survival data comparing nivolumab to docetaxel in previously treated metastatic non-small cell lung cancer (NSCLC) patients, demonstrating improved overall survival: 29% vs. 16% for non-squamous NSCLC and 23% vs. 8% for squamous NSCLC.
需要更多的临床研究来确定治疗持续时间如何影响患者的反应。如果在肿瘤完全收缩或免疫系统自然会保持其抗癌活动后长期需要周期性治疗，尽管早期研究的一些患者在没有进一步治疗的情况下无需进一步治疗超过5年的患者，但仍然需要长期[1]。
Expanding the Scope
The FDA has approved many new or expanded indications for immunotherapies, such as nivolumab, for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who have relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation brentuximab vedotin.
除了更好的理解和扩大当前疗法，还存在重新检查治疗策略的潜在机会。虽然IPILIMIMAB，Nivolumab，Pembrolizumab和Atezolizumab用于各种适应症的批准验证免疫治疗方法，但现在应该考虑这些药物的不同策略。
例如，调整从疾病的前期阶段的治疗的定时可能更有效地攻击肿瘤。治疗也可以扩展到它们的重点和目前的指示之外，看看是否可以在不同的肿瘤类型中看到类似的结果。
Combinations of multiple immunotherapies are also being evaluated to see if they may provide greater efficacy potential, as has been noted in melanoma with the combination of ipilimumab and nivolumab, which increases the two-year overall survival in melanoma from 54% to 64% compared to ipilimumab alone. However, combinations will need to be carefully evaluated not only for efficacy, but also for adverse events due to the potential for increased toxicity.
其他免疫疗法从不同角度接近癌症，比检查点抑制剂，例如癌症疫苗，含彩色病毒和养护细胞转移。在后者，而不是试图通过使用检查点抑制剂刺激体内的T细胞，可以操纵患者自己的T细胞以寻求患者肿瘤细胞上的特异性抗原并杀死它们。该过程涉及将患者自己的T细胞与血液中的分离，然后将嵌合抗原受体（轿厢）遗传地工程到细胞中。
在那些T细胞成倍物之后，将它们重新注入到患者中，在那里它们被引导并破坏肿瘤细胞。初步结果表明，这种方法对具有某些晚期血液癌的成年人的潜力 - 包括儿科急性淋巴细胞白血病 - 当其他治疗不再是一种选择时。
专注于响应者
无论免疫疗法目标还是方法，当免疫系统也可能攻击健康细胞时，自身免疫不良事件仍然是一个问题。获得临床前数据并将其yaboapp体育官网与临床数据组合可能允许更好地理解导致自身免疫反应的特定作用机制。然后，这种观点可以在建立防止或减少这些不利发出的策略方面有价值，并帮助指导设计和有效监测临床试验。尽管存在这些副作用，但医生在治疗过程中早期识别和治疗它们。
Biomarkers也可用于更好的靶患者更容易响应，从而通过根据其生物标志物型材分层和治疗患者来增加治疗窗口。这将通过仅治疗最佳致力的机会来改善治疗响应。目前，PD-L1生物标志物已被用于此类评估，而在与许多肿瘤类型中的潜在反应相关的同时，这不是用于免疫基疗法的唯一相关的生物标志物。其他有前途的免疫疗法生物标志物包括基因组标志物，例如确定新抗原的突变负担和生产，以及免疫应答的基础生物标志物。
临床试验中的回顾性和前瞻性分析有望导致进一步的新型生物标志物发现和应用，并使患者早期相位筛查。然而，需要更多的工作来确定最预测的生物标志物或用于免疫疗法的生物标志物组合。
临床成功的考虑因素
With more drug candidates, possible targets, approaches and mechanisms to explore, the immuno-oncology field holds great promise for the industry and patients, yet has distinct development needs quite unlike any other oncology treatment.
药品developers must consider strategies for identifying patients in an increasingly competitive trial landscape, training and supporting investigators, providing adequate site and patient monitoring and bioinformatic needs to better support the increasing complexity of biomarker studies. Suitable site selection also factors into the equation, in that a site must be able to handle the unique volume, complexity and timeline requirements of an immunotherapy trial.
Past performance in previous trials and relevant oncology experience are key factors to consider when considering suitable sites. With a proprietary knowledgebase that has visibility to more than 40% of the world’s trials, Covance can apply its Xcellerate®信息学套件，以确定用于执行这些专门试验的最佳网站和调查人员。亚博全站官网发现患者也通过获得7500万去鉴定的患者测试结果进行了优化Labcorp.数据库使这些试验最佳地设计和更接近相关的患者人群。
在最粒度的水平，重要的是要注意免疫治疗试验的独特人员配置要求。亚博全站官网调查人员和临床研究伙伴必须了解免疫相关响应标准如何与其他肿瘤治疗的响应标准不同。治疗可能需要更多的时间来产生反应，或者肿瘤可能溶胀（“伪”疾病进展）收缩之前。
为了确保试验合规性，记录良好的计划应概述何时继续或结束基于特定响应模式的治疗。从安全角度来看，现场工作人员应熟悉在研究期间出现的任何免疫相关不良事件（IRAE）的识别，报告和治疗。
强大的临床策略只是复杂方程的一部分。通过新的指示，组合疗法，替代治疗方法以及生物标志物定义的响应标准，我们的领域具有巨大的发现和改善免疫治疗和其管理的能力。这些非常独特的特征造成了巨大和迫在眉睫的挑战，但它是与转化癌症治疗的巨大潜力并改善患者存活结果是相同的潜力。
[1]http://www.news-metical.net/news/20160530/oncologists-combine-two-different-types-of-immunotherapy-to-to-successuly-treat-merastatic-melanoma.aspx.
