Dai Zhi, Liu Xue-Meng, Zhao Yun-Li, Zhao Li-Xing, Luo Xiao-Dong
Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, People's Republic of China.
Nat Prod Bioprospect. 2024 Aug 19;14(1):48. doi: 10.1007/s13659-024-00472-w.
Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.
最近,美国食品药品监督管理局(FDA)进行了一项风险调查,并对所有靶向B细胞成熟抗原(BCMA)和CD19的嵌合抗原受体(CAR)-T细胞疗法加上了黑框警告。那么这是否意味着公众必须冒着患继发性癌症的风险才能接受细胞疗法呢?在此,在不使用慢病毒和专业抗原呈递细胞的情况下,仅通过在CD28共刺激信号下将主要组织相容性复合体(MHC)癌细胞与初始T细胞共培养,成功开发了一种新型的肿瘤特异性T细胞疗法。这些肿瘤特异性T细胞可以通过细胞大小分离,并能从外周血中大量产生,在体外试验中会自发攻击携带相同肿瘤抗原的靶细胞,同时避开其他细胞。此外,在给小鼠回输两次后,它使肿瘤结节明显减少了90%,同时显著提高了总生存期(从30天提高到76天)。这项工作最大程度地避免了继发性癌症和非特异性杀伤的风险,并可能开启天然肿瘤特异性T细胞疗法的革命性开端。