FDA:
Cellular therapy products include cellular immunotherapies, cancer vaccines, and other types of both autologous and allogeneic cells for certain therapeutic indications, including hematopoetic stem cells and adult and embryonic stem cells.
EMA: Cell therapy consists of the administration to humans of autologous living cells (i.e., emanating from the patient himself), or allogeneic cells (therefore coming from another human being) or even xenogeneic cells (coming from an animal). To some extent, these selected cells may have been manipulated or processed to change their biological characteristics, prior to their administration. This definition includes the expansion and activation of autologous cell populations ex vivo (adoptive immunotherapy, for example) and the use of allogeneic or xenogeneic cells contained in microcapsules for protein drug replacement.
Cell therapy products have to be considered as medicinal products needing a marketing authorisation if they are industrially manufactured.
嵌合抗原受体T细胞(Chimeric antigen rerceptor T-cell,CAR-T)是一种经过基因工程改造的T细胞,表达人造CAR而用于免疫治疗。CAR-T治疗的原理如图2所示,由病人血液采集单核细胞,随后将CAR基因转导并进行细胞的体外扩增。回输人体后,表达在T细胞上的嵌合抗原受体赋予T细胞识别肿瘤细胞特定抗原的能力,当CAR结合抗原后,激活CAR-T细胞,使 T 细胞通过直接与肿瘤细胞表面的特异性抗原相结合而激活,通过释放穿孔素、颗粒酶素 B 等直接杀伤肿瘤细胞,同时还通过释放细胞因子募集人体内源性免疫细胞杀伤肿瘤细胞,从而达到治疗肿瘤的目的,而且还可形成免疫记忆 T 细胞从而获得特异性的抗肿瘤长效机制。目前,CAR-T 细胞对多种血液肿瘤显示了非常好的临床效果,对实体瘤治疗也表现出了非常大的潜力。
参考资料
参考法规指南、文献、案例、问答、课程等30+,包括:
June CH, O'Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359(6382):1361‐1365. doi:10.1126/science.aar6711
Jensen, Trine I.; Axelgaard, Esben; Bak, Rasmus O. (June 2019). "Therapeutic gene editing in haematological disorders with CRISPR/Cas9". British
Bruce L. Levine, James Miskin, Keith Wonnacott, Christopher Keir, Global Manufacturing of CAR T Cell Therapy, Molecular Therapy - Methods & Clinical Development, Volume 4, 2017, Pages 92-101
Adrian P. Gee, GMP CAR-T cell production, Best Practice & Research Clinical Haematology, Volume 31, Issue 2, 2018, Pages 126-134
Parker, Kevin R. et al. Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies. Cell, Volume 0, Issue 0