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:Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.
Blood-Brain Barrier in Brain Tumors: Biology and Clinical Relevance.
然而,这些策略大多仅在临床前模型或 1-2 期试验中接受过测试,尚无一种获批用于脑肿瘤的治疗。
血脑屏障(BBB)和脑肿瘤屏障(BTB)等屏障会限制抗肿瘤药物进入脑组织,导致治疗应答不佳。为克服这些屏障,研究者开发了多种技术,包括经鼻或鞘内直接注射物质、化学修饰药物或BBB组成成分、抑制外排泵、利用射频电磁辐射造成物理性BBB破坏、激光诱导热疗(LITT)、聚焦超声(FUS)联合微泡,以及对流增强递送(CED)。但多数策略仅在临床前模型或Ⅰ~Ⅱ期试验中评估,尚无任何一种获批用于脑肿瘤治疗。在脑转移瘤治疗方面,近年研发的多种分子具有更强的BBB穿透能力,例如用于非小细胞肺癌的第三代酪氨酸激酶抑制剂奥希替尼,以及用于乳腺癌的奈拉替尼和图卡替尼;与早期药物相比,这些药物改善了无进展生存期和总生存期。神经干细胞、CAR-T(嵌合抗原受体)策略及免疫检查点抑制剂治疗等前景良好的研究仍在进行。
The presence of barriers, such as the blood-brain barrier (BBB) and brain-tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1-2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.
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