TARGETING AND THERAPY OF TUMORS WITH MONOCLONAL ANTIBODY

用单克隆抗体靶向和治疗肿瘤

• 批准号: 3175437
• 负责人: Tsann Ming Chu
• 金额: $ 10.08万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-15 至 1992-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3175437
• 关键词: adenocarcinoma; antibody specificity; athymic mouse; biological response modifiers; breast neoplasms; cancer registry /resource; carcinoma; cell mediated cytotoxicity; combination cancer therapy; doxorubicin; glycoproteins; histopathology; human therapy evaluation; human tissue; mesothelioma; mixed tissue /cell culture; molecular oncology; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide diagnosis; ovary neoplasms; radioimmunoassay; radiotracer; tumor antigens; xenotransplantation

Monoclonal antibody F36/22 (IgG3, recognizes a glycoprotein with Mr of 700- 1000k) has been shown immunohistochemically to be reactive with all human common epithelial ovarian cancers, while normal ovary expresses no detectable level of immunostain. Human exfoliated ovarian tumor cells are usually disseminating throughtout the entire peritoneal cavity, and represent an ideal target for therapeutic manipulation in a confined compartment. A recently available human ovarian carcinoma xenograft in female athymic mice, NIH:OVCAR-3, expresses antigen recognized by monoclonal antibody F36/22 and resembles the human disease by producing ascites and intra-abdominal carcinomatosis. Using monoclonal antibody F36/22 as the probe and NIH:OVCAR-3 as the in vivo model, we will develop and evaluate effective radioimmunotherapy for the targeting and elimination of peritoneal ovarian tumor seedings. Adriamycin, a commonly used cytotoxic agent in ovarian cancer, will be conjugated to monoclonal antibody F36/22 for intracavity immunochemotherapy of ovarian tumor. Effectiveness of both therapies will be potentiated by biological response modifiers. The proposed approaches to the use of a unique monoclonal antibody in targeting and therapy of ovarian cancer in a confined cavity compartment with little or no communication with other body compartments will generate defined and useful preclinical information. Additionally, data available most recently have suggested the targeting of a repetitive epitope on a breast cancer mucin by McAb F36/22, which was initially generated against human breast cancer cell lines. Since antibody reagent is already available, an immunoassy can be developed easily and evaluated most efficiently on the association between McAb F36/22 and the breast cancer mucin, and the result will be compared with that obtained from an ovarian cancer mucin previously reported by us. Finally, we will elucidate the antigenic determinant(s) of the human prostate specific antigen (PSA), originally reported from this laboratory and the most effective and FDA approved marker for managment of prostate cancer, in order to increase the efficacy of tumor targeting/therapy by monoclonal antibodies already generated.

单克隆抗体F36/22 （IgG3）识别Mr为700-的糖蛋白

项目成果

Serum level of cryptic tumor antigens in breast cancer patients as determined by two monoclonal antibodies (M85/F36) and its comparison with CA 15-3.

两种单克隆抗体（M85/F36）测定乳腺癌患者血清隐性肿瘤抗原水平及其与CA 15-3的比较。

• DOI: 10.1002/jcla.1860030502
• 发表时间: 1989
• 期刊: Journal of clinical laboratory analysis
• 影响因子: 2.7
• 作者: Chu,TM;Constantine,R;Nemoto,T
• 通讯作者: Nemoto,T

Prostaglandin E2-mediated suppression of murine lymphokine-activated killer cell activity generated from tumor-bearing hosts by interferon-gamma.

前列腺素 E2 介导的干扰素-γ 抑制荷瘤宿主产生的鼠淋巴因子激活的杀伤细胞活性。

• 发表时间: 1990
• 期刊: Molecular biotherapy
• 作者: Nakajima,I;Chu,TM
• 通讯作者: Chu,TM

Enhanced cell-mediated cytotoxicity by interferon-gamma and interleukin-2 against syngeneic murine mammary adenocarcinoma.

干扰素-γ 和白细胞介素-2 增强细胞介导的细胞毒性，对抗同基因小鼠乳腺癌。

• 发表时间: 1992
• 期刊: Molecular biotherapy
• 作者: Nakajima,I;Chu,TM
• 通讯作者: Chu,TM

Indirect inhibition of generation of murine lymphokine-activated killer cell activity in splenocyte cultures by interferon-gamma.

通过干扰素-γ 间接抑制脾细胞培养物中鼠淋巴因子激活的杀伤细胞活性的产生。

• 发表时间: 1990
• 期刊: Immunology
• 影响因子: 6.4
• 作者: Chao,TY;Ohnishi,H;Chu,TM
• 通讯作者: Chu,TM

Prostaglandin E2 from macrophages of murine splenocyte cultures inhibits the generation of lymphokine-activated killer cell activity.

来自小鼠脾细胞培养物巨噬细胞的前列腺素 E2 抑制淋巴因子激活的杀伤细胞活性的产生。

• DOI: 10.1159/000217694
• 发表时间: 1991
• 期刊: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
• 作者: Ohnishi,H;Lin,TH;Nakajima,I;Chu,TM
• 通讯作者: Chu,TM