先前的研究發(fā)現(xiàn)，實(shí)驗(yàn)室傳統(tǒng)方法創(chuàng)建的殺傷性T淋巴細(xì)胞因?yàn)樯嬷芷诙滩荒苡行У臍⑺腊┌Y細(xì)胞，成為癌癥治療的障礙。為了克服該問(wèn)題，日本科學(xué)家河本浩及其科研團(tuán)隊(duì)將成人體內(nèi)的殺傷性T淋巴細(xì)胞重組成iPS細(xì)胞，并研究了如何區(qū)分這兩種細(xì)胞。該結(jié)果發(fā)表在《Cell》雜志上。
該研究團(tuán)隊(duì)將皮膚癌中的T淋巴細(xì)胞重組成iPS細(xì)胞，獲得的iPS細(xì)胞在實(shí)驗(yàn)室條件下大量擴(kuò)增并且重新誘導(dǎo)分化為殺傷性T淋巴細(xì)胞。這些殺傷性T淋巴細(xì)胞對(duì)同一類型的皮膚癌細(xì)胞有較好的殺傷作用，同原始淋巴細(xì)胞有相同的基因組，其表面不僅表達(dá)特異性的腫瘤特異性受體還可分泌INF-γ。
科學(xué)家河本浩說(shuō)：“我們已經(jīng)成功的通過(guò)iPS擴(kuò)增出特異殺傷性T淋巴細(xì)胞，下一步我們將要做的是確定在機(jī)體不存在其它殺傷細(xì)胞的情況下，該特異性殺傷細(xì)胞對(duì)腫瘤細(xì)胞的特異性殺傷功能。如果可能的話，將這些細(xì)胞直接注射到患者體內(nèi)達(dá)到治療效果將會(huì)為期不遠(yuǎn)。”
Cancer-specific killer T cells created from induced pluripotent stem cells (iPSC)
Previous research has shown that killer T lymphocytes produced in the lab using conventional methods are inefficient in killing cancer cells mainly because they have a very short life-span, which limits their use as treatment for cancer. To overcome these problems, the Japanese researchers led by Hiroshi Kawamoto and presenting their results in the journal Cell Stem Cellonline today, reprogramed mature human killer T lymphocytes into iPS cells and investigated how these cells differentiate.
The team induced killer T lymphocytes specific for a certain type of skin cancer to reprogram into iPS cells by exposing the lymphocytes to the 'Yamanaka factors'. The 'Yamanaka factors' is a group of compounds that induce cells to revert back to a non-specialized, pluripotent stage. The iPS cells obtained were then grown in the lab and induced to differentiate into killer T lymphocytes again. This new batch of T lymphocytes was shown to be specific for the same type of skin cancer as the original lymphocytes: they maintained the genetic reorganization enabling them to express the cancer-specific receptor on their surface. The new T lymphocytes were also shown to be active and to produce the anti-tumor compound interferon γ.
"We have succeeded in the expansion of antigen-specific T cells by making iPS cells and differentiating them back into functional T cells. The next step will be to test whether these T cells can selectively kill tumor cells but not other cells in the body. If they do, these cells might be directly injected to patients for therapy. This could be realized in the not-so-distant future." explains Dr Kawamoto.
