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:An update on the clinical trial research of immunotherapy for glioblastoma.
采用当前标准治疗,中位总生存期不足 2 年。
多形性胶质母细胞瘤(GBM)是成人常见的原发性恶性脑肿瘤,复发率和死亡率均较高。目前标准疗法下中位总生存期不足2年。近年来,免疫疗法在非小细胞肺癌和黑色素瘤等实体瘤中开始显示良好结果,胶质母细胞瘤免疫治疗也在全面开展,主要包括免疫检查点抑制剂、癌症疫苗、CAR-T 细胞疗法和溶瘤病毒疗法。然而,颅内淋巴系统功能障碍、血脑屏障存在、高度免疫抑制性肿瘤微环境,以及GBM自身低肿瘤突变负荷和高度异质性等特征,严重阻碍了免疫疗法的应用。本综述系统评估近期发表的GBM免疫治疗临床试验结果,批判性分析试验进展和局限,深入探讨有效免疫治疗的当前障碍,并重点介绍可能指导未来治疗开发的有前景临床前研究。
Glioblastoma multiforme (GBM) is a common primary malignant brain tumor in adults, characterized by a high rate of recurrence and mortality. The median overall survival is less than 2 years with the current standard therapy. As immunotherapy has begun to show promising results in solid tumors such as non-small cell lung cancer and melanoma in recent years, immnunotherapy for patients with glioblastoma is also in full swing, which is mainly consisted of immune checkpoint inhibitors, cancer vaccines, chimeric antigen receptor T-cell and oncolytic viral therapy. However, the application of immunotherapy in glioblastoma is severely hampered by cognitive impairment of intracerebral lymphatic system, the existence of blood-brain barrier, highly immunosuppressive tumor microenvironment and GBM's intrinsic features, including low tumor mutation burden and high heterogeneity. This review systematically evaluates recently published clinical trial outcomes of GBM immunotherapy, critically analyses both the progress and limitations of these trials, thoroughly examines current barriers to effective immunotherapy, and highlights promising preclinical studies that may guide future therapeutic development.
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