1998 Fiscal Year Final Research Report Summary
Basic Analysis of Immuno-gene Therapy for Melanoma Using Functional Characteristic of CD82
| Project/Area Number |
09670905
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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 |
Dermatology
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| Research Institution | YAMANASHI MEDICAL UNIVERSITY |
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Principal Investigator |
SHIBAGAKI Naotaka Yamanashi Medical University, School of Medicine, Assistant staff., 医学部, 助手 (40262662)
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Hirofumi Japanese Cancer Institute, Cancer Chemotherapy Center, Chief., 部長 (00189614)
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| Project Period (FY) |
1997 – 1998
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| Keywords | CD82 / MELANOMA / CELL ADHESION / CANCER VACCINATION |
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| Research Abstract |
To define T-cell costimulatory molecules that work in the early phase of T-cell activation, we established monoclonal antibodies (mAbs) that inhibit or enhance T-cell activation by histiocytic leukemia cell line U937. One of the mAbs, 53H5, that recognized both T cells and U937 was identified to bind to CD82 by expression cloning. Functional analyses of CD82 revealed the following : 1) CD82 needs to exist on both T cells and U937 for the full activation of T cells ; 2) CD82 expression is up-regulated on both T cells and U937 by stimulation such as CD3 ligation or PMA treatment ; 3) overexpression of CD82 enhances both homotypic and heterotypic cell adhesion between T cells and U937 ; 4) CD82 signal costimulates T cells and the signal works synergistically with the CD28-mediated T-cell costimulation signal ; 5) in mixed leukocyte reaction (MLR) using U937 as stimulator cells, CD82 overexpression on U937 correlates with the higher allogeneicity of U937 cells ; 6) overexpression of CD82 on melanoma cells enhances heterotypic cell adhesion between melanoma cells and T cells. These results indicate that CD82, expressed on both T cells and antigen presenting cells or target cells, plays an important role not only as a costimulatory molecules in T cells, but also as a cell adhesion molecules.
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