CAR-T细胞基因沉默问题

Veblen

想请问一下CAR-T细胞制备，为什么需要将其中的TRAC和B2M基因沉默掉呢？

niwanmao

CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion.（摘自：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558614/）

Veblen

niwanmao 发表于 2020-3-16 22:12
CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR ex ...

谢谢老师，好像也没具体说到为啥会沉默掉TRAC和B2M，只是说到了结果，沉默掉后增强了CART efficacy. 我想了解的是这两个基因的功能，这两个是会引起GVHD的基因吗？

niwanmao

Veblen 发表于 2020-3-17 22:34
谢谢老师，好像也没具体说到为啥会沉默掉TRAC和B2M，只是说到了结果，沉默掉后增强了CART efficacy. 我想 ...

这两个是抑制T细胞功能的。不是引起GVHD。

Veblen

niwanmao 发表于 2020-3-18 07:50
这两个是抑制T细胞功能的。不是引起GVHD。

好的，谢谢老师，理解了。