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:CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.
胶质母细胞瘤(GBM)是最常见的原发性脑肿瘤,但当前治疗下预后仍然很差。
胶质母细胞瘤(GBM)是最常见的原发性脑肿瘤,但现有治疗下预后仍极差。迄今免疫治疗策略治疗GBM的效果有限,但近期进展带来希望。其中一项免疫治疗进展是嵌合抗原受体(CAR)T细胞疗法:提取患者自体T细胞,经工程化改造表达可识别GBM抗原的特异性受体,再回输患者体内。大量临床前研究显示出有希望的结果,其中多种CAR-T疗法正在针对GBM及其他脑癌开展临床试验。虽然治疗淋巴瘤和弥漫性内生性脑桥胶质瘤等肿瘤的结果令人鼓舞,GBM早期试验尚未显示临床获益。潜在原因包括GBM中特异性抗原数量有限、抗原表达异质,以及抗原特异性治疗开始后肿瘤通过免疫编辑丢失抗原。本文综述CAR-T细胞疗法治疗GBM的现有临床前和临床经验,并讨论开发更有效GBM CAR-T细胞的潜在策略。
Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.
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