1995 Fiscal Year Final Research Report Summary
Basic study for clinical application of anti-ganglioside D2 monoclonal antibody against neuroblastoma
Project/Area Number |
05670668
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Pediatrics
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Research Institution | Nagoya University |
Principal Investigator |
HORIBE Keizo Nagoya University, School of Medicine, Department of Pediatrics, Assistent Professor, 医学部, 講師 (30209308)
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Co-Investigator(Kenkyū-buntansha) |
FUKUDA Minoru Nagoya University, School of Medicine, Department of Pediatrics, Attending Pedia, 医学部, 医員
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Project Period (FY) |
1993 – 1995
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Keywords | Neuroblastoma / Anti-ganglioside D2 antibody / Immunotherapy / Cytokine |
Research Abstract |
In order to apply anti-ganglioside D2 (GD2) mouse monoclonal antibodies (moAb) as a specific therapy for neuroblastoma, 3 kinds of anti-GD2 moAb were studied about the tissue specificity, anti-tumor effect in vitro and in vivo, and its augmentation with hematopoietic cytokines. 1.MoAbs 220-51, A1.410 and 3F8 specifically responded to human neuroblastoma cell lines and tumor samples, and responded only to brain tissue among normal tissues tested. 2.Imaging study with injection of radiolabelled 220-51 revealed its specific consentration to the tumor region in the nude mouse transplanted with neuroblastoma cell lines. 3.All of 220-51, A1.410 and 3F8 were demonstrated the complement dependent cytotoxicity and antibody dependent cellular cytotoxicity against neuroblastoma cell lines. 4.Antibody dependent cellular cytotoxicity by neutorophils was enhanced by reconbinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF). 5.MoAb 220-51 had the inhibition activity against tumor progression by itself. The actvity was inhibited more strongly by the antibody combined with recombinant mouse GM-CSF (rmGM-CSF) or recombinant human granulocyte-CSF (rhG-CSF), and it was inhibited most strongly by the antibody combined with both rmGM-CSF and rhG-CSF. These findings suggested that anti-GD2 moAb must be useful for the clinical application in neuroblastoma therapy.
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