决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs.
Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs.
肿瘤免疫治疗对改善肿瘤患者的预后有显著贡献。
癌症免疫疗法显著改善了癌症患者的预后。免疫疗法包括人表皮生长因子受体2(HER2)靶向治疗、免疫检查点抑制剂(ICI)和嵌合抗原受体修饰T细胞(CAR-T);这些疗法共同利用免疫系统的能力杀伤癌细胞。曲妥珠单抗是一种抗HER2单克隆抗体,可阻断HER2介导的信号传导,主要用于HER2阳性癌症,如乳腺癌、结直肠癌、胆道癌和非小细胞肺癌。免疫检查点抑制剂通过抑制CTLA-4或PD-1与PD-L1结合,使T细胞能够杀伤癌细胞;可用于黑色素瘤、非小细胞肺癌、尿路上皮癌以及头颈癌。T细胞转移疗法主要有两种:TIL(肿瘤浸润淋巴细胞)疗法和CAR-T细胞疗法,后者主要用于B细胞淋巴瘤、白血病和套细胞淋巴瘤。HER2靶向治疗(主要是曲妥珠单抗)可能导致左心室功能障碍,通常可逆且极少危及生命。PD/PDL-1抑制剂可能引发心肌炎,虽罕见,但可能暴发且死亡率高。CAR-T治疗也与多种心脏毒性有关,主要发生于全身性不良反应背景下的细胞因子释放综合征。
Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.
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