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:Challenges in the Treatment of Glioblastoma by Chimeric Antigen Receptor T-Cell Immunotherapy and Possible Solutions.
胶质母细胞瘤(GBM)是成人最致命的脑癌之一,占每年诊断的所有恶性原发性中枢神经系统肿瘤的 48.6%。
胶质母细胞瘤(GBM)是成人最致命的脑癌之一,占每年诊断的原发性恶性中枢神经系统肿瘤的48.6%。即使接受最大安全切除、辅助放疗及替莫唑胺化疗等标准治疗,GBM患者5年生存率仍低于10%,亟需新的治疗方式。过去十年,CAR-T(CAR-T)细胞免疫治疗血液系统恶性肿瘤取得重大进展。迄今美国FDA已批准6种CAR-T产品治疗B细胞急性淋巴细胞白血病、淋巴瘤和多发性骨髓瘤等血液肿瘤。CAR-T临床试验数量也大幅增加,其中超过80%来自中国和美国。CAR-T治疗液体肿瘤取得成功后,其治疗包括GBM在内多种实体瘤的临床疗效也在探索中,但目前GBM中的结果仍不及血液肿瘤。与其他实体瘤类似,GBM CAR-T仍面临肿瘤异质性、免疫抑制性TME和CAR-T持久性等挑战。因此,需要开发克服这些困难的策略,加速GBM CAR-T从实验室走向临床。
Glioblastoma (GBM), one of the most lethal brain cancers in adults, accounts for 48.6% of all malignant primary CNS tumors diagnosed each year. The 5-year survival rate of GBM patients remains less than 10% even after they receive the standard-of-care treatment, including maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide. Therefore, new therapeutic modalities are urgently needed for this deadly cancer. The last decade has witnessed great advances in chimeric antigen receptor T (CAR-T) cell immunotherapy for the treatment of hematological malignancies. Up to now, the US FDA has approved six CAR-T cell products in treating hematopoietic cancers including B-cell acute lymphoblastic leukemia, lymphoma, and multiple myeloma. Meanwhile, the number of clinical trials on CAR-T cell has increased significantly, with more than 80% from China and the United States. With its achievements in liquid cancers, the clinical efficacy of CAR-T cell therapy has also been explored in a variety of solid malignancies that include GBMs. However, attempts to expand CAR-T cell immunotherapy in GBMs have not yet presented promising results in hematopoietic malignancies. Like other solid tumors, CAR-T cell therapies against GBM still face several challenges, such as tumor heterogeneity, tumor immunosuppressive microenvironment, and CAR-T cell persistence. Hence, developing strategies to overcome these challenges will be necessary to accelerate the transition of CAR-T cell immunotherapy against GBMs from bench to bedside.
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