Novel Cancer Immunotherapies and Antitumor Immunity
Novel Cancer Immunotherapies and Antitumor Immunity
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新型癌症免疫疗法和抗肿瘤免疫
DOI：
10.1155/2019/3742061
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发表时间：
2019-07
影响因子：
4.1
通讯作者：
Abbas Hussein A
中科院分区：
文献类型：
--
作者：
Zhao Lei;Zhang Jianjun;Xu Liang;Abbas Hussein A
近年来免疫检查点阻断治疗在临床上的成功表明，阻断肿瘤相关的免疫抑制和启动肿瘤特异性免疫可能是开发新型抗癌免疫疗法的关键。深入了解如何启动和调节肿瘤特异性免疫对于开发新的癌症免疫疗法至关重要。在这个问题上，有3篇综述文章，涵盖了关键的免疫工具：双特异性抗体，自然杀伤（NK）细胞和新抗原。S. Chen等人综述了目前对双特异性抗体的理解及其产生这些抗体的时间发展、作用机制、在癌症医学中的应用以及这些药物的经济影响。S. Matosevic回顾了NK细胞作为过继免疫细胞疗法的出现，以及其从病毒和非病毒载体工程化背后的技术背景。R.- Y. Pan等人回顾了识别肿瘤新抗原的探索，以及如何在临床前和临床模型中基于免疫治疗的平台中利用这些发现。为了补充上述文章，本期还包括6篇研究文章，涵盖癌症免疫学和治疗学的不同方面。I. Poláková等人证明了头颈癌患者血液和肿瘤组织中淋巴和骨髓成分的深度免疫分析的实用性。Y. Wu等人鉴定了可引发基于细胞毒性T淋巴细胞的应答的基于HLA-A2的表位。本文还包括动物研究中靶向EGFR的两种单克隆抗体。W. Qiu et al.讨论了一种靶向EGFR的新型单克隆抗体，在动物模型中与伊立替康联合使用时，其安全性和疗效优于西妥昔单抗。Y. Yang等人证明了在食管癌的鼠模型中融合基于假单胞菌的免疫毒素与基于EGFR的新型抗体的功效。Q. Zhang等人证明了多激酶抑制剂regorafenib与CAR-NK细胞的组合如何在结直肠癌细胞系中引起反应。总的来说，这些文章整合了当前癌症管理中基于免疫疗法的不同方面。我们目前对免疫疗法和抗肿瘤免疫的理解仍然需要大量的改进。需要更多的研究来确定对免疫疗法和基于CAR的治疗反应的生物标志物，以便无反应者可以避免不良事件的风险。还有其他检查点阻断剂可以用于癌症治疗吗？与基于CAR的治疗相比，哪些患者将受益于双特异性抗体？联合免疫疗法与靶向治疗或化疗是否有作用？这些问题与癌症患者的决策过程相关，需要更深入和广泛的研究来解决。尽管如此，目前的证据强烈表明，基于免疫的疗法是有效的，但了解其活性的背景对其成功至关重要。
Recent success of immune-checkpoint blockade therapy in clinic has revealed that blockade of tumor-associated immunosuppression and initiation of tumor-specific immunity could be critical for the development of novel immunotherapies against cancer. Deep understanding of how to initiate and modulate tumor-specific immunity would be critical for the development of novel cancer immunotherapies. In this issue, there are 3 review articles that cover key immunological tools: bispecific antibodies, natural killer (NK) cells, and neoantigens. S. Chen et al. reviewed the current understanding of bispecific antibodies and its chronological development to produce these antibodies, mechanism of action, application in cancer medicine, and the economic impact of these drugs. S. Matosevic reviewed the emergence of NK cells as an adoptive immune-cellular therapy and the technical background behind its engineering from viral and nonviral vectors. R.-Y. Pan et al. reviewed the quest to identify tumor neoantigens and how to leverage these findings in immunotherapy-based platforms in preclinical and clinical models. In order to complement the aforementioned articles, this issue also included 6 research articles that span different aspects of cancer immunology and therapeutics. I. Poláková et al. demonstrated the utility of deep immune-profiling of lymphoid and myeloid components in the blood and tumor tissue of head and neck cancer patients. Y. Wu et al. identified HLA-A2-based epitopes that can elicit cytotoxic T lymphocyte-based responses. Two monoclonal antibodies targeting EGFR in animal studies were also included here. W. Qiu et al. discussed a novel monoclonal antibody targeting EGFR with better safety and efficacy profiles than cetuximab when combined with irinotecan in animal models. Y. Yang et al. demonstrated the efficacy of fusing Pseudomonas-based immunotoxin with a novel EGFRbased antibody in a murine model of esophageal cancer. Q. Zhang et al. demonstrated how combining the multikinase inhibitor, regorafenib, with CAR-NK cells could elicit responses in colorectal cancer cell lines. Collectively, these articles integrate different aspects of immune-based therapies in the current management of cancer. Our current understanding of immune therapies and antitumoral immunity still requires significant refining. More studies are needed to identify the biomarkers of response to immunotherapies and CAR-based treatments so that nonresponders could be spared the risks of adverse events. Are there other checkpoint blockers that one could leverage in cancer treatment? Which patients would benefit from bispecific antibodies compared to CAR-based treatments? Is there a role for combination immune-based therapies with targeted therapy or chemotherapy? These are questions that are relevant in the decision process for cancer patients and require more in-depth and extensive research to address. Nevertheless, the current evidence strongly suggests that immune-based therapies work but understanding the context of its activity is vital for its success.