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:Neurologic Complications of Cancer and Its Treatment.
本文讨论癌症相关神经系统并发症的诊断和治疗,包括(1)脑、脊髓和软脑膜转移的诊断与管理;
**目的:**本文讨论癌症相关神经系统并发症的诊断与治疗,包括:(1)脑、脊髓及软脑膜转移的诊断和管理;(2)传统细胞毒性、生物制剂及靶向治疗的毒性,重点关注免疫疗法(免疫检查点抑制剂和嵌合抗原受体[CAR]T细胞疗法);(3)副肿瘤综合征;以及(4)急性和长期后遗症,包括癫痫发作、卒中、神经病变,以及青少年和儿童癌症治疗的长期影响。 **最新进展:**脑转移灶的基因特征可能与原发肿瘤不同,部分脑转移可对全身治疗而非局部治疗产生应答。免疫检查点抑制剂的应用日益增加,也使包括副肿瘤神经综合征在内的免疫介导性神经系统并发症发生率上升。CAR-T细胞疗法最初用于白血病和淋巴瘤,目前正应用于更多癌症,可引起细胞因子释放综合征和免疫效应细胞相关神经综合征等并发症;针对这些并发症已有特定治疗方案。 **要点:**及时识别全身性癌症及其不断演进治疗直接或间接引起的神经系统并发症,对改善结局至关重要。神经科医生应熟悉传统化疗、免疫检查点抑制剂和CAR-T细胞疗法常见及罕见的神经毒性。
OBJECTIVE: This article discusses the diagnosis and treatment of cancer-related neurologic complications including (1) diagnosis and management of brain, spinal, and leptomeningeal metastases; (2) toxicities of conventional cytotoxic, biologic, and targeted therapies with a focus on immunotherapies (immune checkpoint inhibitors and chimeric antigen receptor [CAR] T-cell therapy); (3) paraneoplastic syndromes; and (4) acute and long-term sequelae, including seizures, stroke, neuropathy, and long-term effects of young adult and childhood cancer treatment. LATEST DEVELOPMENTS: Brain metastases can differ genetically from the primary neoplasm, with some responding to systemic rather than local therapies. Increasing use of immune checkpoint inhibitors has increased the incidence of immune-mediated neurologic complications, including paraneoplastic neurologic syndromes. CAR T-cell therapy, initially developed for leukemia and lymphoma, is being applied to an increasing range of cancers and can cause complications such as cytokine release syndrome and immune effector cell-associated neurologic syndrome, for which specific therapeutic protocols are available. ESSENTIAL POINTS: Prompt recognition of direct and indirect neurologic complications of systemic cancers and their evolving treatments is essential to maximize favorable outcomes. Neurologists should be familiar with common and rare neurologic toxicities of conventional chemotherapy, immune checkpoint inhibitors, and CAR T-cell therapy.
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