| Project/Area Number |
07671346
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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 |
General surgery
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| Research Institution | Fukuoka University |
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Principal Investigator |
HIDESHIMA Teru 2nd Dept. of Surgery, School of Med., Fukuoka University, Assistant Professor, 医学部, 講師 (00238312)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Hidechika Dep. of Moleculer Biology, School of Med., Nagoya City Univ., Professor, 医学部, 教授 (30160683)
SHIRAKUSA Takayuki 2nd Dept. of Surgery, School of Med., Fukuoka University, Professor, 医学部, 教授 (20038863)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | bispecific Antibody / cytotoxicity / CEA / carcinoma / CD3 / 細胞障害反応 |
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| Research Abstract |
The anti-human CEA x anti-human CD3 bispecific antibody, OH-1, recognized both CEA expressed on the KATOIII gastric cancer cell line and CD3 expressed on T-lymphocytes as determined by flowcytometry. OH1-mediated cytolysis was analyzed by a ^<51>Cr-release assay. When ^<51>Cr-labeled target KATOIII cells were incubated for 6 hr with effector PBMC that had been pretreated with OH1 for 45 min. at 4ﾟC,the percentage specific lysis significantly increased compared to non-treated PBMC.When ^<51>Cr-labeled KATOIII cells were incubated with OH1-treated PBMC for 3,6,10 and 20 hr at the E/T ratio of 100/1, the specific lysis were 11.6%, 19.1%, 21.9 and 39.0%, respectively. There was not only time dependence of specific lysis, but also significant difference between OH1-treated and non-treated PBMC (p<0.01). Furthermore, PBMC obtained from eight cases of gastric and colo-rectal carcinoma were used as effector cells treated with or without OH1 at the E/T ratio of 100/1, specific lysis were 25.4% and 12.1%, respectively and there was significant defference between the each group (p<0.01).
To evaluate the activity of OH1 in vivo., 3*10^6 KATOIII cells were intra-abdominally trnsplanted to severe combined immunodeficiency (SCID) mice. The OH1-treated PBMC prolonged the survival time of the SCID mice compared to that of non-treated PBMC.However, there was not significant difference between the each group. These resullts thus suggested the usefulness of OH-1 to augment the cytotoxicity of CD3 positive T-cells against the CEA positive target cells both in vitro.
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