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癌症免疫疗法毒性综述 II:过继细胞疗法、激酶抑制剂、单克隆抗体和溶瘤病毒。

A Review of Cancer Immunotherapy Toxicity II: Adoptive Cellular Therapies, Kinase Inhibitors, Monoclonal Antibodies, and Oncolytic Viruses.

机构信息

Department of Emergency Medicine, Division of Medical Toxicology, Cook County Health, 1950 W Polk Street, 7th Floor, Chicago, IL, 60612, USA.

Toxikon Consortium, Chicago, IL, USA.

出版信息

J Med Toxicol. 2022 Jan;18(1):43-55. doi: 10.1007/s13181-021-00835-6. Epub 2021 Apr 5.

DOI:10.1007/s13181-021-00835-6
PMID:33821435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8021214/
Abstract

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.

摘要

癌症的免疫疗法在种类、药物和适应证方面都取得了快速发展。通过利用人体固有免疫系统的各个方面,免疫疗法提高了多种癌症患者的预期寿命和生活质量。过继性细胞疗法,包括嵌合抗原受体 T 细胞(CAR T)疗法,涉及对患者 T 细胞进行基因工程,从而能够靶向肿瘤细胞。在进行淋巴清除治疗之前和输注 CAR T 细胞之后,需要对患者进行监测,以检测治疗的毒性。特定的毒性包括细胞因子释放综合征和神经毒性,两者都可能危及生命。对于中重度毒性,应考虑使用托珠单抗和/或皮质类固醇。激酶抑制剂毒性可能是由于“靶内”效应或“靶外”效应对多个器官系统的影响,因为这些药物具有共同的蛋白质表位。治疗是针对特定器官的。在使用单克隆抗体治疗期间,常会出现输注反应,且治疗主要是支持性的。溶瘤病毒的临床经验有限,但已观察到局部反应,包括蜂窝织炎和全身流感样综合征,但通常是轻微的。尽管由于新型免疫疗法药物引起的不良反应的临床经验在不断增加,但对其机制和潜在毒性的最新了解至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3596/8758887/1394e6104d3b/13181_2021_835_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3596/8758887/1394e6104d3b/13181_2021_835_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3596/8758887/1394e6104d3b/13181_2021_835_Fig1_HTML.jpg

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