前日阿朱參加了易貿(mào)醫(yī)療舉行的第三屆細(xì)胞治療產(chǎn)業(yè)峰會(huì)，會(huì)上聽到來(lái)自博生吉楊林教授關(guān)于CAR-NK產(chǎn)業(yè)化生產(chǎn)遇到的挑戰(zhàn)。楊林教授一如既往的為大家?guī)?lái)精彩報(bào)告讓很多人重新把目光投向了CAR-NK細(xì)胞療法。

雖然CAR-NK細(xì)胞療法不是第一次被提及到，他的類似UCAR-T的體外異體擴(kuò)增優(yōu)勢(shì)也深受研究者喜愛。但是CAR-NK細(xì)胞自身也存在著體內(nèi)無(wú)法大量擴(kuò)增的先天性缺陷限制了其快速的發(fā)展。

那么楊林教授為什么一直力挺CAR-NK的產(chǎn)業(yè)化應(yīng)用呢？

關(guān)于CAR-NK的優(yōu)勢(shì)和功能前面的文章都有提及到，那么在CAR-T、NK、NK-92細(xì)胞直接到底有多大的功能區(qū)別，阿朱惡補(bǔ)了一下過往的文章，在2014年發(fā)表在Oncoimmunology雜志上的一篇題為：Are natural killer cells superior CAR drivers?中試圖找到答案。

下圖是文章中總結(jié)的三種細(xì)胞的特點(diǎn)：

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）非病毒法轉(zhuǎn)染效率可以達(dá)到50%

2）技術(shù)簡(jiǎn)單而不受太多條件限制

3）避免病毒載體的殘留造成的癌基因激活或者是插入突變

4）細(xì)胞獲得更加容易

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.

目前已經(jīng)有識(shí)別多種靶點(diǎn)的CAR-NK細(xì)胞正在進(jìn)行臨床前和臨床研究，而且聯(lián)合治療獲得更大的療效是CAR-T/CAR-NK的共性。

不管楊林教授處于如何的考慮，我們都有理由相信CAR-NK的前景非常樂觀。當(dāng)我們手上真正擁有了有效安全的CAR-T、TCR-T、CAR-NK、PD-1/PD-L1四大法寶的時(shí)候，才是攻克癌癥難題的時(shí)候，加油吧騷年！

 參考文獻(xiàn)：doi:  10.4161/onci.28147