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 china: innovations, challenges, and strategic pathways.
在中国,国产CAR-T疗法进展迅速,临床结局已达到与全球基准相当的水平,B细胞恶性肿瘤的ORR为79-89%,多发性骨髓瘤的12个月PFS为64%。
癌症免疫治疗改变了肿瘤学,其中 CAR-T 已成为血液系统恶性肿瘤个体化治疗的基石。在中国,国产 CAR-T 快速发展,临床结局已达到全球基准水平:B 细胞恶性肿瘤 ORR 为 79%–89%,多发性骨髓瘤 12 个月 PFS 为 64%。尽管取得这些成功,CAR-T 用于实体瘤仍受抗原异质性、免疫抑制性微环境及靶向肿瘤外毒性阻碍。为克服这些障碍,中国率先探索创新策略,包括双靶点 CAR-T、分泌免疫调节细胞因子的装甲 CAR-T,以及与中医药的协同整合;中医药可通过抑制髓源性抑制细胞和减少 CRS 增强 CAR-T 疗效。值得注意的是,临床前研究显示,黄芩与 CAR-T 联合可使肺癌模型肿瘤消退率从 40% 提高至 65%。与此同时,中国通过“1+3+N”多层级支付体系和区域保险试点等政策创新改善可及性,使患者费用降低 50%。对自动化生产和全球监管协调的战略投入,进一步使中国成为高性价比 CAR-T 开发的领先者。但实体瘤靶向、国际市场整合及长期安全监测仍面临挑战。未来方向包括精准工程设计、AI 驱动治疗优化和跨境合作,以推进下一代疗法。通过平衡创新、可负担性和政策灵活性,中国有望推动全球癌症免疫治疗发展,并应对血液系统和实体恶性肿瘤领域未满足的需求。
Cancer immunotherapy has transformed oncology, with CAR-T cell therapy emerging as a cornerstone of personalized treatment for hematologic malignancies. In China, rapid advancements in domestically developed CAR-T therapies have achieved clinical outcomes comparable to global benchmarks, with overall response rates (ORR) of 79-89% in B-cell malignancies and 64% 12-month progression-free survival in multiple myeloma. Despite these successes, CAR-T application in solid tumors remains hindered by antigen heterogeneity, immunosuppressive microenvironments, and on-target/off-tumor toxicity. To address these barriers, China has pioneered innovative strategies, including dual-target CAR-T constructs, armored CAR-Ts secreting immunomodulatory cytokines, and synergistic integration with traditional Chinese medicine, which enhances CAR-T efficacy by inhibiting myeloid-derived suppressor cells and reducing cytokine release syndrome. Notably, preclinical studies demonstrate that Huangqin increases tumor regression rates from 40 to 65% in lung cancer models when combined with CAR-T therapy. Concurrently, China is reshaping accessibility through policy innovations such as the "1 + 3 + N" multi-tiered payment system and regional insurance pilots, which reduce patient costs by 50%. Strategic investments in automated manufacturing and global regulatory harmonization further position China as a leader in cost-effective CAR-T development. However, challenges persist in solid tumor targeting, international market integration, and long-term safety monitoring. Future directions emphasize precision engineering, AI-driven treatment optimization, and cross-border collaborations to advance next-generation therapies. By balancing innovation, affordability, and policy agility, China is poised to drive the global evolution of cancer immunotherapy while addressing unmet needs in both hematologic and solid malignancies.
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