2006 Fiscal Year Final Research Report Summary
Combined interleukin-12 and Dendritic cell neoadjuvant immunotherapy for hepatocellular carcinoma in immunosuppressed mice
| Project/Area Number |
17390372
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
MAEHARA Yoshihiko Kyushu University, Graduate School of Medical Sciences, Professor (80165662)
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| Co-Investigator(Kenkyū-buntansha) |
TAKETOMI Akinobu Kyushu University, Hospital, Research Associate (70363364)
SOEJIMA Yuji Kyushu University, Hospital, Research Associate (30325526)
OKANO Shinji Kyushu University, Hospital, Research Associate (10380429)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Living donor liver transplantation / Hepatocellular carcinoma / Interleukin-12 / Dendritic cell / Immunosuppression |
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| Research Abstract |
When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. One of the reasons is the decrease of immunity by immunosuppressed agents. The aim of this study is to evaluate the efficacy of combined interleukin-12 (IL-12) and dendritic cell (DC) neoadjuvant immunotherapy for HCC under immunosuppression. C3H mice (H-2k) were s. c. implanted with MH134 cells (H-2k) and we treated the established HCC with combined intratumoral electroporation-mediated murine IL-12 (mIL-12) and bone marrow derived DC-based immunotherapy. 7 days after this therapy, we started the FK506 i. p. injection to put into the state of the immunity control. Our results demonstrated combined therapy with mIL-12 and DC produced highly amounts of intratumoral mIL-12 and IFN-γ and showed stronger MH134-specific cytolytic activity more than mIL-12 therapy alone and DC therapy alone. Combined therapy with mIL-12 and DC induced a significant suppression of the growth of s. c. established HCC into which the mIL-12 vector and DC had been directory injected compared to mIL-12 therapy alone and DC therapy alone, as well as reduced both spontaneous lung and liver metastases. In particularly, combined therapy with mIL-12 and DC did not show any spontaneous lung and liver metastases. These results suggest combined IL-12 and DC neoadjuvant immunotherapy is a potent effective strategy to prevent recurrences of HCC in immunosupressed patients undergone liver transplantation.
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