| Project/Area Number |
09044306
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
広領域
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| Research Institution | Osaka University |
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Principal Investigator |
KANEDA Yasufumi Osaka University, Factory of medicine, Professor, 医学部, 教授 (10177537)
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| Co-Investigator(Kenkyū-buntansha) |
CURIEL David University of Alabama at Birmingham, Cancer Center, Director, 癌研究所, 部長
MITANI Kohnosuke University of California Los Angeles, Associate Professor, 医学部, 助教授
SALEH Mansour University of Alabama at Birmingham, Cancer Center, Associate Director, 癌研究所, 副部長
HOON Dave John Wayne Cancer Insitute, Director, 分子細胞免疫学, 部長
HOON Dave ジョンウェイン癌研究所, 分子細胞免疫学, 部長
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | melanoma vaccine / liposome / gene therapy / tumor antigens / HVJ-liposome / 遺伝子発現 / SP100 / DNAワクチン / RNAワクチン / 遺伝子治療 / 癌抗原 / 遺伝子導入 / HVJ-リポソーム |
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| Research Abstract |
We isolated melanoma specific antigen cDNA from melanoma patient cDNA library by PCR.MAGE-1 and 3 were introduced into mouse muscle by HVJ-liposomes and could induce antibody rtesponse tu tumor antigen. Then, we tested preventive effects of cancer gene vaccination in tumorbearing mice. Op 100 is immunogenic and shown to induce both antibody and cytotoxic T cell (CTL) responses in humans. The gplOO DNA vaccine was used in a mouse melanoma model to assess immunity against the B16 melanoma of C57BL/6 mice. Intrasmuscular injection of the DNA-HVJ-AVE liposomes induced both anti-gp100 anyibody and CTL responses. Gp 100 DNA-HVJ-AVE liposome immunization delayed tumor development in mice challenged with B16 melanoma cells. Mice limmunized with gplOO DNA-HVJ-AVE liposomes survived longer compared with control mice immunized with HVJ-AVE liposome alone. Next, an RNA melanoma vaccine was investigated to induce protective immunity in a mouse-melanoma model when administered by various routes. The human melanoma-associated antigen gplOO mRNA was in vitro synthesized by pSFV3 expression vector and encapsulated in HVJ- liposomes. Immunization by either intramuscular or intradermal injection of the mRNA-HVJ-liposomes was ineffective for the induction of protective immunity against B16 melanoma challenge. However, immunization by direct injection of the gplOO mRNA HVJ-liposomes into mouse spleen induced both anti-gp 100 Ab and CTL responses against melanoma. Immunizations with gplOO mRNA into the spleen delayed tumor growth and significantly prolonged survival compared to control treated mice. These pre-clinical studies demonstrate that an RNA tumor antigen vaccine strategy has potential application for human cancer treatment and prevention.
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