(Published in 2018)
A research team led by Professor Shin Kaneko at the Center for iPS Cell Research and Application (CiRA), Kyoto University, has succeeded in enhancing the anti-tumor effect of regenerative T-cells from human iPS cells (iPSCs) by genome editing. <\/p>\n\n\n\n
In this study, regenerative T-cells\u2019 ability to attack tumor cells has been confirmed in a mouse study, which is a giant step towards clinical application. Professor Kaneko\u2019s team is an advanced team working under T-CiRA, a joint research program with Takeda Pharmaceutical Company.<\/p>\n\n\n\n
Current T-cell immunotherapy<\/strong> When genes encoding<\/em> a tumor-reactive T-cell receptor (TCR) are introduced<\/em> into a patient\u2019s T-cells, the number of the T-cells that attack a certain tumor can be increased. It is expected that the T-cells will attack and heal a certain tumor by transplantation.<\/p>\n\n\n\n Since each T-cell <\/em>expresses one type of TCR, it can recognize only one type of antigen and does not respond to other antigens (antigen specificity). Therefore, TCR-transduced T-cells can specifically attack tumor cells.<\/em><\/p>\n\n\n\n Limitations of current T-cell immunotherapy<\/strong><\/em> Results of this study<\/strong> To solve this problem, they knockout RAG2 gene in T-iPSCs by using a genome editing system (CRISPR\/Cas9) and have succeeded in blocking the unwanted rearrangement. The genome-edited T-cells were injected into tumor-bearing mice. Recipients of the genome-edited T-cells showed delayed tumor growth and longer survival compared to non-treated mice.<\/p>\n\n\n\n Secondly, they regenerate T-cells from monocyte-derived iPSCs that were transduced with an antigen-specific TCR. These regenerative T-cells expressed the transduced TCR without RAG2 gene knockout.<\/p>\n\n\n\n The TCR-transduced T-cells were injected into tumor-bearing mice. Recipients of the TCR-transduced iPSC-derived T-cells showed delayed tumor growth and superior survival compared to a group treated by TCR-transduced primary T-cells and a non-treated group. Furthermore, the group treated by the TCR-transduced iPSC-derived T-cells showed lower incidence of tumor metastasis.<\/p>\n\n\n\n Their study could contribute to safe and effective regenerative T-cell immunotherapies.<\/p>\n\n\n\n Immunotherapy with T-cell-derived iPSCs<\/strong> (Published in 2018)A research team led by Professor Shin Kaneko at the Center for iPS Cell Research and Application (CiRA), Kyoto University, has succeeded in enhancing the anti-tumor effect of regenerative T-cells from human iPS cells (iPSCs) by genome editing. In this study, regenerative T-cells\u2019 ability to attack tumor cells has been confirmed in a […]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[131],"tags":[36,157,163,164],"class_list":["post-1205","post","type-post","status-publish","format-standard","hentry","category-cancer","tag-ipsc","tag-t-cell","tag-cancer","tag-immunotherapy"],"yoast_head":"\n
T-cells are a type of immune cell. T-cells proliferate and eliminate<\/em> non-self cells such as virus-infected cells and tumor cells.<\/p>\n\n\n\n
TCR- transduced<\/em> T-cells from a patient\u2019s own cells are less proliferative, and the number of them is limited. Moreover, these cells\u2019 aggressiveness against tumor cells is weakened.<\/p>\n\n\n\n
Firstly, the research team produced T-iPSCs from tumor-reactive T-cells in a patient\u2019s blood, and then regenerate T-cells from the T-iPSCs. They found that these regenerative T-cells lose antigen specificity due to additional TCR gene rearrangement in the DP cell stage, one of precursor stages between iPSCs and T-cells, and they cannot attack tumor cells.<\/p>\n\n\n\n
iPSCs can proliferate indefinitely. If we produce iPSCs from antigen-specific T-cells (T-iPSCs) and regenerate T-cells from T-iPSCs, we can get many proliferative T-cells. For safe and effective immunotherapy, it is important to regenerate T-cells which exhibit the same antigen specificity as the original T-cells. This therapy utilizes a patient’s own T-cells and can only be used for the patient<\/em>.<\/p>\n","protected":false},"excerpt":{"rendered":"