1997 Fiscal Year Final Research Report Summary
Basic Reseach for the Establishment of Gene Immunotherapy Against Advanced Neuroblastoma
| Project/Area Number |
08457229
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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 |
Pediatrics
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MATSUMURA Takafumi Kyoto Pref.Univ.of Medicine, Pediatrics, Assistant Professor, 医学部, 講師 (40219481)
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| Project Period (FY) |
1996 – 1997
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| Keywords | neuroblastoma / gene immunotherapy / allogeneic MHC gene / MHC抗原 |
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| Research Abstract |
Introduction :
Neuroblastoma is considered as an immunogenic tumor, because of the clinical evidence of spontaneous regression, presence of TAAs and more lymphocytic infiltration in regressing tumors. Therefore, the modification of tumor immunogenicity by transfer with allogeneic MHC gene could enhanced the host anti-tumor immunity.
Methods & Results :
1)S3 is a highly tumorigenic subclone of a C-1300 NB cell line from A/J mouse (H-2Kk). S3neo4 was a control line transfected with neor, while S3Kb4C3 was a transfectant with both nCMVintKb (carrying H-2Kb) and neor.
2)A/J mice were subcutaneously inoculated with tumor cells. Tumor rejection was observed in 5/20 miceinoculated with S3Kb4C3, but in none of mice inoculated with control cells. THe survival improvement was observed in mice inoculated with S3Kb4C3 compared to control mice. All mice survived rejected parent S3.
3)In 51Cr release assay, splenocytes from mice immunized with S3Kb4C3 effectively lysed S3Kb4C3 as well as S3, but not S1509a from A/J mouse.
4)Mice were immunized by intraperitoneal inoculation with INF-g-and MMC-treated control cells or S3Kb4C3, and were injected with HVJ-liposome into the established S3 tumors. Tumor regression was observed in 5/10 mice injected with HVJ-liposome containingn CMVintKb (H-2Kb protein expression in tumor cells injected with nCMVintKb was comfirmed by FACS), but in none injected with HVJ-liposome containing control DNA.
Conclusion :
Transfer with allogeneic MHC gene into tumor cells invitro as well as in vivo could be an effective gene immunotherapy and feasible for clinical application for neuroblastoma.
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[Publications] Matsumura, T., Ishida, H., Kadono, Y., Ohmizono, Y., Hosoi, H., Sawada, T.and Salgaller, M.L.: "Gene expression of the MAGE-1-encoding human melanoma antigen in pediatric tumors." Proceedings of American Association for Cancer Research. 35. 497 (1994)
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