先前的研究发现，实验室传统方法创建的杀伤性T淋巴细胞因为生存周期短不能有效的杀死癌症细胞，成为癌症治疗的障碍。为了克服该问题，日本科学家河本浩及其科研团队将成人体内的杀伤性T淋巴细胞重组成iPS细胞，并研究了如何区分这两种细胞。该结果发表在《Cell》杂志上。
该研究团队将皮肤癌中的T淋巴细胞重组成iPS细胞，获得的iPS细胞在实验室条件下大量扩增并且重新诱导分化为杀伤性T淋巴细胞。这些杀伤性T淋巴细胞对同一类型的皮肤癌细胞有较好的杀伤作用，同原始淋巴细胞有相同的基因组，其表面不仅表达特异性的肿瘤特异性受体还可分泌INF-γ。
科学家河本浩说：“我们已经成功的通过iPS扩增出特异杀伤性T淋巴细胞，下一步我们将要做的是确定在机体不存在其它杀伤细胞的情况下，该特异性杀伤细胞对肿瘤细胞的特异性杀伤功能。如果可能的话，将这些细胞直接注射到患者体内达到治疗效果将会为期不远。”
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.
