1988 Fiscal Year Final Research Report Summary
Analysis of immunological characteristics of human small cell lung cancer using monoclonal antibodies and its clinical applications.
| Project/Area Number |
61570681
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Tokyo Medical University |
|---|
Principal Investigator |
NAKAMURA Haruhiko Tokyo Medical College, Faculty of Medicine, Instructer, 医学部, 助手 (80183523)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NIITSUMA Masayuki Tokyo Medical College, Faculty of Medicine, Lecturer (70150662)
HAYATA Yoshihiro Tokyo Medical College, Faculty of Medicine, Professor (30074470)
KAWAMURA Ichita Tokyo Medical College, Faculty of Medicine, Professor (70074599)
|
|---|
| Project Period (FY) |
1986 – 1988
|
| Keywords | Monoclonal Antibody / Lung Cancer / Small Cell Lung Cancer / Cell Membrane Antigen / Tumor Specific Antigen / 癌免疫療法 |
|---|
| Research Abstract |
Analysis of membrane surface antigens of small cell lung cancer(SCLC) using several kinds of monoclonal antibodies revealed that SCLC has Leu-7 antigen which is originally possessed by some subsets of lymphocytes and EMA which is possessed by epithlial cells. Moreover SCLC very frequently reacted with NCC-Lu-243 and 246 monoclonal antibodies which recognize the common antigen shared with neuroendocrine tissues. These facts suggest that SCLC is a unique tumor which has both epithelial and neuroendocrine characteristics. Since NCC-Lu 243 LIgG2a) generously provided by the National Cancer Center is the most specific murine monoclonal antibody against SCLC at present, we examined the possibility of its clinical applications. This antibody has complement dependent cytotoxicity(CDC),and it has also antibody dependent cell mediated cytotoxicity(ADCC) using a patient's lymphocytes as effector cells. ADCC increased especially in low concentration areas of antibody when we pretreated effector cells with IL-2. Concerning the anti-tumor effects of this antibody against SCLC transplanted in nude mice, inhibitory effects of tumor growth were observed following intra-tumor or intra-peritoneal injection when the volume of the tumor was less than 300mm^3. But when the tumor was larger, there was hardly any antitumor effects. We produced an anti-cancer agent, Daunomycin conjugated monoclonal antibody, and examined its antitumor effects both in vitro and in vovo. To obtain good results, we should improved conjugated agents , way of administration, and methods of conjugation. As a toxicity test for NCC-Lu-243 antibody, 5mg/kg of antibody was administered to a monkey intravenously 3 times for an interval of one week. Severe allergic reactions were not seen, but temporary hepatic and renal dysfunctions were recognized. This result suggests the potentiality of the clinical use of this monoclonal antibody.
|
