1991 Fiscal Year Final Research Report Summary
Novel cancer therapy using human monoclonal antibody against human epidermal growth factor receptor
| Project/Area Number |
02807185
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | Hiroshima University |
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Principal Investigator |
OKAMOTO Tetsuji Hiroshima Univ. Dental Hospital, Assistant Prof., 歯学部附属病院, 講師 (00169153)
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| Co-Investigator(Kenkyū-buntansha) |
TAKADA Kazuaki Hiroshima Univ. Scho. of Dent. Prof., 歯学部, 教授 (30029970)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Epidermal growth factor / Epidermal Growth Factor Receptor / Monoclonal antibody / Oral Cancer / Squamous Cell Carcinoma / Salivary Gland Adenocarcinoma / Immuno-histchemical / Lymphokine-activated killer cells |
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| Research Abstract |
Two mouse hybridomas secreting monoclonal immunoglobulin g and m antibodies to epidermal growth factor receptors(EGFR)of A431 cells were obtained from one fusion experiment.
One of the antibodies, 12-93 IgG inhibited the binding of[il-EGF to A431 cells by at least 95%. Another antibody, 10-77 IgM had no effect on the binding of EGF to A431 cells. Both of antibodies immunopreclpitated EGFR from Triton X-100 extracts of A431 membranes.
We tested 12-93 IgG which. inhibits the binding of EGF to its receptor in vitro and in vivo for intrinsic growth promoting activity for squamous cell carcinoma cells and salivary gland adenocarcinoma cells which exhibit opposite growth response to nanomolar concentration of eGF.
Furthermore, the expression of EGFR in normal oral mucosa, squamous cell carcinoma, normal salivary gland and salivary gland tumors was determined by immuno-histchemical studies using 12-93.
We have found monoclonal antibody which inhibits the binding of EGF inhibited the growth of oral squamous cell carcinoma cells and adenocarcinoma cells derived from salivary gland in serum-free culture. Furthermore it also inhibited the formation of these tumors which transplanted in athymic mice.
More research is required into the mechanisms by which receptor antibodies cell killing in vivo and into the Tpossible toxic effects of receptor antibodies on normal cells. However, the results obtained are thus far encouraging and indicate that monoclonal antibodies to receptors for growth factors, hormones and transport proteins may eventuallv prove to be viable therapeutic agents. This approach represents a viable alternative to generating tumor-specific monoclonal antibodies.
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Research Products
(10 results)
