2003 Fiscal Year Final Research Report Summary
Isolation of human antibodies targeting to immunocytes from phage library and regulation of immune response
| Project/Area Number |
13672325
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Kagoshima University |
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Principal Investigator |
ITO Yuji Kagoshima University, Faculty of Engineering, Associate Professor, 工学部, 助教授 (60223195)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMURA Kazuhisa Kagoshima University, Faculty of Engineering, Professor, 工学部, 教授 (80127240)
NAKASHIMA Toshihiro The Chemo-Sero-Therapeutic Research Institute, Research group leader, 研究室長
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| Project Period (FY) |
2001 – 2003
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| Keywords | Costimulatory molecules / human antibody / phage library / vaccine / antigen presenting cell / T cell / antagonist / targeting |
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| Research Abstract |
The aims of this study are the isolation of human antibodies directed to the costimulatory molecules on the lymphocytes, the establishment of the targeting and the control of the immune system by using antibodies, and their applications for DNA vaccine development. We succeeded in the isolation of anti B7RP-1 antibodies which could inhibit the costimulatory signal between ICOS and B7RP-1 by human antibody phage display library and are now applying for a patent. The obtained three antibodies could actually repress the T cell proliferation which was induced by anti CD3 antibody stimulation. We also developed other human antibodies that were specific to CD86, a costimulator ligand for CD28 and are now under preparation for a patent. The antibodies mentioned here can function as not only antagonist blocking the costimulatory signal but also targeting molecule to the antigen presenting cells (APC), because APC express abundantly such CD86 and B7RP-1 molecules, and such targeting ability is very important for the effective vaccine development to lead the antigens efficiently to the APC. We are now investigating the new vaccine developing studies by use of our human antibodies. As a preliminary experiment, we constructed a gene of fusion protein of extracellular domain of CTLA-4 (targeting molecule to APC) and human Fc (antigen) and immunized it through skin on mice as DNA vaccine. Consequently high antibody response to the antigen was obtained in the case of the administration of CTLA-4-Fc fusion, as compared with the administration of Fc (antigen) only. These results indicate that the targeting of the antigen to the APC give the promising effect in the vaccine efficacy.
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