2012 Fiscal Year Final Research Report
Development of novel cancer cell vaccine using GM-CSF gene-transuduced IPS cells targeting cancer stem cells
| Project/Area Number |
23790446
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Kyushu University |
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Principal Investigator |
INOUE Hiroyuki 九州大学, 生体防御医学研究所, 助教 (80529967)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 癌幹細胞 / iPS細胞 / 腫瘍免疫療法 / GM-CSF / 遺伝子治療 / 肺癌 |
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| Research Abstract |
Our results of in vitro assays demonstrated that non-transmissible recombinant Sendai virus-mediated mouse GM-CSF gene transfer to iPS (iPS/GM) cells was effective to produce abundant GM-CSF in vitro（200～ng/106cells/24 hrs）and iPS/GM-CSF cells maintained their stemness in terms of morphology and antigenicity as evidenced by the expression levels of SSEA-1,Oct3/4 and alkaline phosphatase similar to those seen in unmodified iPS cells. Our results of in vivo studies using immunocompetent mice demonstrated that mice treated with both prophylactic and therapeutic vaccination using irradiated iPS/GM-CSF (ir.iPS/GM-CSF) cells significantly suppressed the tumor growth of subcutaneously transplanted syngeneic LLC mouse poorly immunogenic lung cancer in the left flank. Of note, during these treatments described above, no serious adverse events were observed with lack of liver and kidney dysfunctions as evidenced by biochemical analysis as well as absence of loss of body weight, suggesting its relative tolerability of use of iPS cells as vaccine cells. Furthermore, in vivo depletion assays showed that the antitumor effect observed in mice treated with ir.iPS/GM-CSF cells was significantly abrogated by depleting CD4+T or CD8+T cells, demonstrating its partial dependence on T cell-mediated cellular antitumor immunity. In conclusion, this is the first report that demonstrated a therapeutic antitumor efficacy of normal fibroblast-derived iPS cell vaccines including iPS/GM cells, providing possible implications that these novel vaccine strategy using iPS cells could induce CSCs associated antigens-specific antitumor immunity and be a promising prophylactic or therapeutic anticancer modality
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[Presentation] Novel cancer immunotherapy using induced pluripotent stem cells genetically engineered to produce GM-CSF2012
Author(s)
Ayumi Wanatabe, Hiroyuki Inoue, Chika Sakamoto, Megumi Narusawa, Shohei Miyamoto, Makoto Inoue, Keisuke Okita, Koichi Takayama, Mamoru Hasegawa, Yoichi Nakanishi, Shinya Yamanaka, and Kenzaburo Tani
Organizer
第71回日本癌学会学術総会
Place of Presentation
ロイトン札幌
Year and Date
20120919-21
