TARGETING AND THERAPY OF TUMORS WITH MONOCLONAL ANTIBODY

单克隆抗体F36/22（IgG 3，识别Mr为700- 1000的糖蛋白） 1000 k）已被证明在化学上与所有人类 常见的上皮性卵巢癌，而正常卵巢表达no 免疫染色的可检测水平。 人卵巢癌脱落细胞 通常扩散到整个腹膜腔， 代表了一个理想的目标，治疗操纵在一个有限的， 车厢 一种最近可用的人卵巢癌异种移植物， 雌性无胸腺小鼠NIH：OVCAR-3表达单克隆抗体识别的抗原 抗体F36/22，并通过产生腹水而类似于人类疾病， 腹腔内癌病 用单克隆抗体F36/22作为免疫原， 探针和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靶向和消除腹膜 卵巢恶性肿瘤 阿霉素，一种常用的细胞毒性药物， 卵巢癌，将与单克隆抗体F36/22结合， 卵巢肿瘤腔内免疫化疗 两者的有效性 生物反应调节剂将增强治疗。 的 所提出的使用独特的单克隆抗体靶向 在一个狭窄的腔室中治疗卵巢癌， 或者没有与其他身体隔室的通信将产生限定的并且 有用的临床前信息。 此外，最近获得的数据 已经提出了靶向乳腺癌上的重复表位 用抗人乳腺癌单克隆抗体F36/22制备的粘蛋白 癌细胞系。 由于抗体试剂已经可用， 免疫测定可以很容易地开发，并在 单克隆抗体F36/22与乳腺癌粘蛋白的相关性研究 将与先前从卵巢癌粘蛋白获得的比较 由我们报道。 最后，我们将阐明的抗原决定簇（S） 人前列腺特异性抗原（PSA），最初报道，从这个 实验室和最有效的和FDA批准的标志物管理 前列腺癌，以增加肿瘤的疗效 通过已经产生的单克隆抗体进行靶向/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.