2013 Fiscal Year Final Research Report
Anti-tumor immunotherapy targeting a cancer stem cell-specific protein for small cell lung cancer
| Project/Area Number |
23591141
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Ko 新潟大学, 医歯学総合病院, 教授 (80207802)
TSUCHIDA Masanori 新潟大学, 医歯学系, 教授 (60293221)
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| Project Period (FY) |
2011 – 2013
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| Keywords | DDX3X / 小細胞肺癌 / 抗腫瘍免疫療法 |
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| Research Abstract |
[Background] Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. We previously reported that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133+ murine melanoma cells exhibiting biological CSC features. [Results] Five of 15 LD-SCLC patients possessed DDX3X-responsive effector T cells. CD4+ effector T cells obtained from peripheral blood of 5 LD-SCLC secreted significantly more IFNgamma upon DDX3X antigen stimulation in the presence of CD11c+ autologous dendritic cells. effector T cells from one LD-SCLC patient responded to DDX3X. In contrast, effector T cells obtained from ED-SCLC patients or healthy volunteers never responded to DDX3X. DDX3X-primed CD4+ T cells mediated potent antitumor therapeutic efficacy in murine models.
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