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:A Review of Cancer Immunotherapy Toxicity II: Adoptive Cellular Therapies, Kinase Inhibitors, Monoclonal Antibodies, and Oncolytic Viruses.
A Review of Cancer Immunotherapy Toxicity II: Adoptive Cellular Therapies, Kinase Inhibitors, Monoclonal Antibodies, and Oncolytic Viruses.
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癌症免疫治疗的类别、药物和适应证迅速扩展。免疫治疗利用机体先天免疫系统的某些机制,改善了多种癌症患者的预期寿命和生活质量。过继性细胞疗法包括CAR-T(CAR-T)细胞治疗,通过基因工程改造患者 T 细胞,使其靶向肿瘤细胞。治疗前淋巴细胞清除期间及 CAR-T 输注后均需监测患者,以发现治疗毒性。特定毒性包括细胞因子释放综合征和神经系统毒性,两者都可能危及生命。出现中度至重度毒性时应考虑托珠单抗和/或皮质类固醇。激酶抑制剂可因共有蛋白表位产生“靶内”或“脱靶”效应,影响多个器官系统,治疗需针对具体器官。单克隆抗体治疗期间常见输注反应,处理主要为支持治疗。溶瘤病毒的临床经验有限;已观察到蜂窝织炎等局部反应以及流感样全身症状,但通常较轻。随着新型免疫治疗药物相关不良反应的临床经验不断增加,及时掌握其机制和潜在毒性仍至关重要。
Immunotherapy for cancer has undergone a rapid expansion in classes, agents, and indications. By utilizing aspects of the body's innate immune system, immunotherapy has improved life expectancy and quality of life for patients with several types of cancer. Adoptive cellular therapies, including chimeric antigen receptor T (CAR T) cell therapy, involve the genetic engineering of patient T cells to allow for targeting of neoplastic cells. Monitoring of patients during the lymphodepletion prior to therapy and following CAR T cell infusion is necessary to detect toxicity of therapy. Specific toxicities include cytokine release syndrome and neurologic toxicity, both of which may be life-threatening.
Tocilizumab and/or corticosteroids should be considered for moderate to severe toxicity. Kinase inhibitor toxicity can occur as "on target" effects or "off target" effects to multiple organ systems due to shared protein epitopes. Treatments are organ-specific. Infusion reactions are common during treatment with monoclonal antibodies and treatment is largely supportive.
Clinical experience with oncolytic viruses is limited, but local reactions including cellulitis as well as systemic influenza-like syndromes have been seen but are typically mild. Although clinical experience with adverse effects due to newer immunotherapy agents is growing, an up-to-date understanding of their mechanisms and potential toxicities is critical.
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