CAR-T、NK、NK-92细胞之间的区别

前日阿朱参加了易贸医疗举行的第三届细胞治疗产业峰会,会上听到来自博生吉杨林教授关于CAR-NK产业化生产遇到的挑战。杨林教授一如既往的为大家带来精彩报告让很多人重新把目光投向了CAR-NK细胞疗法。

虽然CAR-NK细胞疗法不是第一次被提及到,他的类似UCAR-T的体外异体扩增优势也深受研究者喜爱。但是CAR-NK细胞自身也存在着体内无法大量扩增的先天性缺陷限制了其快速的发展。

那么杨林教授为什么一直力挺CAR-NK的产业化应用呢?

关于CAR-NK的优势和功能前面的文章都有提及到,那么在CAR-T、NK、NK-92细胞直接到底有多大的功能区别,阿朱恶补了一下过往的文章,在2014年发表在Oncoimmunology杂志上的一篇题为:Are natural killer cells superior CAR drivers?中试图找到答案。

下图是文章中总结的三种细胞的特点:

而文章中提到的:

Although the challenge of introducing CAR-coding genes into sufficient numbers of circulating NK cells may be overcome at some point, NK-92 cells present an open cellular platform for CAR-based immunotherapy.11 The transfection efficiency of NK-92 cells is about 50%, even with non-viral methods.10Besides being technically more simple and under less-constraining regulations, avoiding viral vectors eliminates the risks of oncogene activation and insertional mutagenesis. Upon sorting, CAR-expressing NK-92 cells can be enriched to obtain a population near-to-exclusively composed of NK-92 carrying the CAR of interest.

1)非病毒法转染效率可以达到50%

2)技术简单而不受太多条件限制

3)避免病毒载体的残留造成的癌基因激活或者是插入突变

4)细胞获得更加容易

So far, NK-92 cells have been efficiently transduced with a number of different CAR-coding constructs (Table 2) and pre-clinical studies in xenotransplanted immunodeficient mice have demonstrated the potential therapeutic effects of this approach. Several centers are gearing up to test whether CAR-expressing NK cells can keep up with their T-cell counterparts. Eventually, we might even discover that both these cell types have their place in the multimodal approach that is required to eliminate cancer and control its recurrence.

目前已经有识别多种靶点的CAR-NK细胞正在进行临床前和临床研究,而且联合治疗获得更大的疗效是CAR-T/CAR-NK的共性。

不管杨林教授处于如何的考虑,我们都有理由相信CAR-NK的前景非常乐观。当我们手上真正拥有了有效安全的CAR-T、TCR-T、CAR-NK、PD-1/PD-L1四大法宝的时候,才是攻克癌症难题的时候,加油吧骚年!