PARAMETERS INVOLVED IN THE TUMOR TARGETING OF MONOCLONAL ANTIBODIES

单克隆抗体肿瘤靶向涉及的参数

• 批准号: 3916372
• 负责人: P H HAND
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916372
• 关键词: cellular oncology; chemical binding; disease /disorder model; drug administration routes; gene expression; hepatocellular carcinoma; human subject; immunoconjugates; melanoma; model design /development; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer transplantation; peritoneum neoplasm; radiotracer

One of the problems observed in studies using radiolabeled MAbs for detection of human tumors is the relatively low percent of the injected dose of monoclonal antibody (MAb) per gram of tumor. Recent studies in in vivo model systems for melanoma and hepatoma, and clinical trials involving hepatoma patients have suggested enhanced deposition of radiolabeled antibody in tumors pretreated with external irradiation. One major goal of this project is to identify parameters that optimize binding of MAbs to carcinoma cells in vivo. We have recently initiated studies to determine the effect of exposure of carcinomas to external irradiation prior to localization of tumors by MAb conjugates. These studies include evaluation of the effect of external irradiation on (a) growth of carcinoma xenografts, (b) cellular integrity and the expression of TAG-72 at the cellular level, and, (c) binding of MAb B72.3 to carcinoma xenografts. One approach to the treatment of patients with peritoneal carcinoma may be direct infusion into the peritoneal cavity of radiolabeled antibody conjugates. In comparison to intravenous MAb administration, this method may improve the percent of the injected MAb dose per gram of tumor and may lead to less radiolabeled antibody in the bone marrow and, therefore, less toxicity to the patient. The second major goal of this project is to develop an in vivo model system to study immunotherapy of human carcinoma in the peritoneal cavity. These studies will include (a) determination of the animal species eliciting a pattern of clearance of MAb from the blood most comparable to that observed in the human, (b) development of a human peritoneal carcinoma xenograft in an animal model, and (c) determination of the utilty- of intraperitoneally administered MAb conjugates for therapy of carcinoma.

在使用放射性标记单克隆抗体的研究中观察到的一个问题是， 用于检测人类肿瘤的是相对较低的百分比， 每克肿瘤的单克隆抗体（MAb）注射剂量。 黑色素瘤和肝癌体内模型系统的最新研究， 涉及肝癌患者的临床试验表明， 放射性标记抗体在预处理的肿瘤中的增强沉积 外部辐射。 该项目的一个主要目标是 鉴定优化MAb与癌结合参数 体内细胞。 我们最近开始研究， 癌在放疗前接受外照射的影响 通过MAb缀合物定位肿瘤。 这些研究包括 评价外部辐照对（a） 癌异种移植物，（B）细胞完整性和 （c）MAb B72.3与TAG-72在细胞水平的结合，以及 异种移植癌 腹膜癌患者的治疗方法之一 可以将放射性标记的 抗体缀合物。 与静脉注射MAb相比 这种方法可以提高注射的百分比。 MAb剂量/克肿瘤，可能导致放射性标记较少 骨髓中的抗体，因此， 病人 该项目的第二个主要目标是开发一个 研究人肿瘤免疫治疗体内模型系统 腹膜腔。 这些研究将包括（a） 动物物种的确定引发了一种模式， MAb从血液中的清除率与观察到的最相似 在人中，（B）人腹膜癌的发展 异种移植物在动物模型中的效用，和（c）确定 腹膜内施用的MAb缀合物用于治疗 carcinoma.