CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cardiotoxicity of Cancer Treatments: Focus on Anthracycline Cardiomyopathy.
Cardiotoxicity of Cancer Treatments: Focus on Anthracycline Cardiomyopathy.
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在开发新疗法和优化现有疗法用于抗癌方面已取得重大进展。这些疗法的成功应用以及癌症患者生存期的延长,伴随着新心脏毒性反应的报道以及对既往已知心脏并发症更深入的描述。针对特定促癌基因的单克隆抗体免疫疗法、CAR-T 细胞以及免疫检查点抑制剂已被开发用于对抗癌细胞,但它们也可能对心脏产生脱靶效应。其中一些心脏毒性被认为是由非特异性免疫激活和炎症损伤所致。与免疫疗法相关的心脏毒性是相对较新的实体不同,关于蒽环类药物诱导的心肌病已有大量文献。
在此,我们简要概述免疫疗法的心脏毒性,目的是将其与蒽环类心肌病区分开来。这一点尤其重要,因为肿瘤治疗的扩展给确定癌症幸存者心功能障碍的病因带来了更大的诊断挑战,这些幸存者有多重癌症治疗史,包括蒽环类药物和免疫疗法同时或随时间序贯给药。随后,我们基于主要来自小鼠模型的实验数据,对蒽环类心肌病发病机制的相关假说进行聚焦综述。对其发病机制的深入理解可能促进新策略的开发,以识别易患蒽环类心肌病的患者,同时使心脏低风险患者能够接受其癌症的最佳治疗。
Significant progress has been made in developing new treatments and refining the use of preexisting ones against cancer. Their successful use and the longer survival of cancer patients have been associated with reports of new cardiotoxicities and the better characterization of the previously known cardiac complications.
Immunotherapies with monoclonal antibodies against specific cancer-promoting genes, chimeric antigen receptor T cells, and immune checkpoint inhibitors have been developed to fight cancer cells, but they can also show off-target effects on the heart. Some of these cardiotoxicities are thought to be due to nonspecific immune activation and inflammatory damage. Unlike immunotherapy-associated cardiotoxicities which are relatively new entities, there is extensive literature on anthracycline-induced cardiomyopathy.
Here, we provide a brief overview of the cardiotoxicities of immunotherapies for the purpose of distinguishing them from anthracycline cardiomyopathy. This is especially relevant as the expansion of oncological treatments presents greater diagnostic challenges in determining the cause of cardiac dysfunction in cancer survivors with a history of multiple cancer treatments including anthracyclines and immunotherapies administered concurrently or serially over time.
We then provide a focused review of the mechanisms proposed to underlie the development of anthracycline cardiomyopathy based on experimental data mostly in mouse models. Insights into its pathogenesis may stimulate the development of new strategies to identify patients who are susceptible to anthracycline cardiomyopathy while permitting low cardiac risk patients to receive optimal treatment for their cancer.
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