TARGETING AND THERAPY OF TUMORS WITH MONOCLONAL ANTIBODY

单抗F36/22(IgG3，识别MR为700的糖蛋白- 1000k)已被免疫组织化学证明与所有人类 常见上皮性卵巢癌，而正常卵巢表达NO 可检测到的免疫染色水平。人卵巢脱落的肿瘤细胞 通常扩散到整个腹膜腔，而且 代表了治疗操作的理想靶点 车厢。新近建立的人卵巢癌异种移植模型 雌性裸鼠NIH：OVCAR-3表达单抗识别的抗原 抗体F36/22，与人类疾病相似，产生腹水和 腹内癌病。用单抗F36/22作为抗体 Probe和NIH：OVCAR-3作为体内模型，我们将开发和评估 有效的放射免疫治疗在腹膜靶向清除中的应用 卵巢肿瘤种子细胞。阿霉素，一种常用的细胞毒剂 卵巢癌，将与单抗F36/22偶联，用于 卵巢肿瘤的腔内免疫化疗。两者的有效性 生物反应调节剂将加强治疗。这个 在靶向中使用独特的单抗的建议方法 和卵巢癌的密闭腔内治疗 否则，不会与其他车厢通信生成已定义的 有用的临床前信息。此外，最新可用的数据 建议以乳腺癌上的重复表位为靶点 单抗F36/22产生的粘蛋白，最初是针对人乳房产生的 癌细胞系。由于抗体试剂已经可用，因此 免疫分析可以很容易地开发，并且可以在 单抗F36/22与乳腺癌粘液的相关性及检测结果 将其与以前从卵巢癌粘液中获得的结果进行比较 由我们报道。最后，我们将阐明沙门氏菌的抗原决定簇(S) 人类前列腺特异性抗原(PSA)，最初是从这里报道的 实验室和FDA批准的最有效的管理标志 前列腺癌，以增加肿瘤的疗效 通过已经产生的单抗进行靶向/治疗。

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.