Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity.
Monoclonal Antibody-Based Immunotherapy and Its Role in the Development of Cardiac Toxicity.
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DOI：
10.3390/cancers13010086
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发表时间：
2020-12-30
期刊：
影响因子：
5.2
通讯作者：
Sadayappan S
中科院分区：
文献类型：
--
作者：
Kumar M;Thangavel C;Becker RC;Sadayappan S
过去二十年来，免疫疗法在癌症患者治疗中的应用取得了显着改善，并延长了许多患者的寿命。单克隆抗体是用作免疫疗法的合成蛋白，用于治疗和管理癌症，需要全面了解癌症生物学和宿主的免疫系统。然而，单克隆抗体激活的免疫反应可以针对非特异性癌细胞，导致频繁的免疫相关不良事件，从而导致癌症患者出现永久性疾病。免疫相关的不良事件会带来心脏毒性的风险，包括单克隆抗体免疫治疗期间和之后的高血压、心力衰竭、心律失常和左心室功能障碍。此外，心脏病和癌症的死亡率高达47%，因此必须采用可靠、灵敏且与临床相关的模型来评估癌症免疫药物的疗效和安全性以及预防心脏毒性。免疫疗法是癌症患者最有效的治疗选择之一。五种特定类别的免疫疗法，包括基于细胞的嵌合抗原受体 T 细胞、检查点抑制剂、癌症疫苗、基于抗体的靶向疗法和溶瘤病毒。免疫疗法可以提高癌症患者的生存率。然而，与此同时，它们可能会在一些癌症患者中在免疫治疗后五到十年内引起炎症并促进不良的心脏免疫调节和心力衰竭。在这篇综述中，我们讨论了与免疫治疗相关的心脏毒性。我们还建议使用人类诱导的多能干细胞衍生的心肌细胞/心脏基质祖细胞和心脏类器官培养物作为创新的实验模型系统，以（1）模拟临床治疗，产生可重复的数据，以及（2）促进免疫治疗诱导的早期和晚期心脏毒性生物标志物的识别。最后，我们介绍了组学衍生的大量数据和心脏生物学的整合，作为发现新的高效无毒免疫疗法的途径。
The application of immunotherapies to treat cancer patients has significantly improved over the last two decades and extended many patients’ life spans. Monoclonal antibodies are synthetic proteins employed as immunotherapies to treat and manage cancers that require a complete understanding of cancer biology and the host’s immune system. However, activated immune responses, by monoclonal antibodies, can target nonspecific cancer cells, causing frequent immune-related adverse events that can lead to permanent disorders among cancer patients. The immune-related adverse events pose a risk of cardiac toxicity that includes hypertension, heart failure, arrhythmias, and left ventricular dysfunction during and after monoclonal antibody immunotherapy. Moreover, with the mortality rate of 47% attributed to heart disease and cancer, it is imperative to employ reliable, sensitive, and clinically relevant models for efficacy and safety assessment of immune drugs for cancer and the prevention of cardiotoxicities. Immunotherapy is one of the most effective therapeutic options for cancer patients. Five specific classes of immunotherapies, which includes cell-based chimeric antigenic receptor T-cells, checkpoint inhibitors, cancer vaccines, antibody-based targeted therapies, and oncolytic viruses. Immunotherapies can improve survival rates among cancer patients. At the same time, however, they can cause inflammation and promote adverse cardiac immune modulation and cardiac failure among some cancer patients as late as five to ten years following immunotherapy. In this review, we discuss cardiotoxicity associated with immunotherapy. We also propose using human-induced pluripotent stem cell-derived cardiomyocytes/ cardiac-stromal progenitor cells and cardiac organoid cultures as innovative experimental model systems to (1) mimic clinical treatment, resulting in reproducible data, and (2) promote the identification of immunotherapy-induced biomarkers of both early and late cardiotoxicity. Finally, we introduce the integration of omics-derived high-volume data and cardiac biology as a pathway toward the discovery of new and efficient non-toxic immunotherapy.
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Chen, Yongjing;Hu, Zhenhua;Zhang, Xueguang
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