1996 Fiscal Year Final Research Report Summary
Induction of tumor specific cytotoxic T lymphocyte by using transfer of co-simulatory molecule gene
| Project/Area Number |
07457150
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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 |
Respiratory organ internal medicine
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
SETOGUCHI Yasuhiro Juntendo Univ.Dept of Respir.Med.Instructor, 医学部, 助手 (90206649)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Miyuki Juntendo Univ.Dept of Immunol.Instructor, 医学部, 助手 (90255654)
TAMAKI Yumi Juntendo Univ.Dept of Respir.Med.Instructor, 医学部, 助手 (60266046)
KIRA Shiro Juntendo Univ.Dept of Respir.Med.Professor, 医学部, 教授 (20095011)
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| Project Period (FY) |
1995 – 1996
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| Keywords | gene trasfer / adenovirus vector / co-stimulatory molecule / CD80 / CD86 / cytotoxic T lymphocyte / cancer / 癌 |
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| Research Abstract |
Interaction between the costimulatory molecule B7-1 (CD80) on antigen-presenting cells and its counter-receptor CD28 on T lymphocyte plays a key role in the induction of cell-mediated immune responses including cancer. Many solid tumor lack expression of B7-1 and this has been suggested to contribute to the failure of immune recognition of these diseases. Based on this knowledge, we hypothesized that co-stimulatory signal delivered through B7-1 or B7-2 molecule expressed on lung cancer cells using replication deficient adenovirus vector (Ad) would induce tumor-specific cytotoxic T lymphocyte (CTL). To evaluate this hypothesis, we constructed two Ads ; AdCMVhB7 (am E1^- Ad5 based vector containing human B7-1 cDNA driven by cytomegalovirus immediate early promoter and enhancer) ; AdNull (above same vector withour expression of exogenous gene) as control. Theoretical advantages of Ad consist in capacity of high efficient gene transduction. Using these Ads, generation of tumor specific CTL
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was studied in a primary syngeneic mixed lymphocyte tumor culture by using both lung cancer cells and peripheral blood lymphocytes obtained from patients with lung cancer. Inoculation of lung cancer cells with 10 multiplicity of infection of AdCMVhB7 resulted in rapid and efficient cell surface expression of B7-1 molecule (>90% of cell at 24h). Cytolytic activity of lymphocytes by using ^<51>Cr-releasing assay (E/T=40) demonstrated that effector lymphocytes induced by hB7-1(+)lung cancer cells treated with AdCMVhB7 could lyse 45% parental lung cancer cells hB7-1(-) with a maximum lysis of 62%, in addition, the effector lymphocytes could not lyse the irrelevant syngeneic fibroblast. In countrast, effector lymphocytes induced by lung cancer cells treated with AdNull as control virus or PBS as control could not lyse parental lung cancer cells at all. Furthermore, cytolytic activity of the effector lymphocytes induced by B7-1 transduced lung cancer cells was inhibited by addition of anti-CD3 antibody (10ug/ml). These data suggested that effector lymphocytes induced by lung cancer treated with AdCMVhB7 have a character of tumor-specific CTL.Adenovirus mediated-hB7-1 gene transfer may be a useful means for gene therapy for lung cancer in application of adoptive immunotherapy. Less
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Research Products
(14 results)
