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 cells: engineered immune cells to treat brain cancers and beyond.
恶性脑肿瘤属于治疗难度最大的恶性肿瘤类型。
恶性脑肿瘤是最难治疗的恶性肿瘤之一。目前常见治疗方案为手术后接受放疗和/或化疗,但患者中位生存情况不佳。近期多种肿瘤免疫治疗的发展令人乐观,提示免疫策略或可帮助脑癌患者。嵌合抗原受体(CAR)T细胞利用抗体或受体配体的肿瘤靶向特异性,引导T细胞发挥细胞溶解功能。研究者已发现多种免疫疗法潜在靶分子,包括但不限于EGFRvIII、IL13Rα2和HER2。血液系统恶性肿瘤患者接受CAR T细胞治疗取得显著临床反应,引发了将该方法用于实体瘤治疗的兴趣。迄今研究结果支持CD19靶向CAR T细胞具有极高临床反应率;脑肿瘤早期临床研究显示其安全性和疾病修饰活性证据,并有望进一步进步以最终惠及患者。然而,若干变异因素似乎减缓了CAR T细胞治疗脑癌的进展。本综述全面分析CAR T细胞治疗脑癌的前景,包括设计和递送考量、当前临床与临床前研究进展、遇到的问题及潜在解决方案。
Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13R 2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells' promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.
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