2004 Fiscal Year Final Research Report Summary
Clinical application of the molecular target therapy for natural occurring tumors in small animals.
| Project/Area Number |
15380213
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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 |
Clinical veterinary science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OHNO Koichi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (90294660)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (60163804)
SATOH Hitoshi The University of Tokyo, The Institute of Medical Science, Assistant, 医科学研究所, 助手 (70183829)
OKUDA Masaru Yamaguchi University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (10325243)
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| Project Period (FY) |
2003 – 2004
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| Keywords | gene therapy / p53 / molecular target therapy / adenovirus / CTLA-4 / dendritic cells / drug resistance |
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| Research Abstract |
Induction of tumor cell death by gene transfer
1.Construction of Canine p53-adenoviral vector for gene transfer and its anti-tumor effect
Canine p53 cloned in our laboratory was inserted cosmid vector and recombinant adenovirus was constructed. The recombinant adenoviral vector had cytoadal effect against canine osteosarcoma cell line in a viral dose dependent manner. The recombinant canine p53 adenovirus only showed additive effect against tumor cells when used with chemothepeutic agents.
2.New molecular target for anti-tumor gene therapy
As new molecular targets for anti-tumor gene therapy, thymus and activation-regulated chemokine (TARC) and activation-induced cytidine deaminase (AID) was cloned in dogs. Furthermore, the recombinant expression plasmid containing CTLA-4-Fce fusion protein was constructed and its binding ability to IgE was confirmed.
3.Investigation of in vivo gene transfer methods
As a basic investigation of in vivo gene transfer into dogs, gene expression plasmid containi
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ng marker cDNA was inoculated into muscle of dogs and its efficacy of expression was determined. The expressed marker protein was seen only at injection sites, indicating lesional gene transfer methods for tumor bearing dogs was recommended.
Immune-gene therapy based on the destruction of immuno-tolerance
Feline dendritic cells (DC) was isolated and cultured for the basic research of adoptive immune-therapy using memory T cells. As a results, feline dendritic cells can be isolated and cultured by adding IL-4 and GM-CSF to PBMC and its phenotype and function were investigated. CTL induced by DCs were also investigated.
Development of therapy for multi-drug resistance in chemotherapy in dogs and cats
As a basic research for the treatment of multi-drug resistance, PgP protein in canine lymphoma has been investigated Furthermore, mutation of p53 gene and canine lymphoma was also examined. As a result, the mutation of p53 gene was correlated with the drug resistance of canine lymphoma, however, it is not associated with the expression of PgP protrein. Less
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