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: 3813408
• 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/3813408
• 关键词: antibody specificity; bone marrow disorder; cellular oncology; chemical binding; chemical synthesis; disease /disorder model; drug administration routes; drug adverse effect; hepatocellular carcinoma; human tissue; immunoconjugates; immunosuppression; melanoma; model design /development; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer radionuclide therapy; neoplasm /cancer transplantation; peritoneum neoplasm; radiopharmacology; radiotracer; xenotransplantation

The overall goal of this project is the delineation of parameters involved in in vivo targeting of monoclonal antibodies. These studies will involve determination of the optimal route of inoculation of antibody as well as the antibody form. Major emphasis will be placed on the pharmacokinetics of plasma clearance of recombinant/chimeric monoclonal antibodies and their ability to target tumors. 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 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 the pattern most comparable to that observed in the human of MAb clearance from the blood, (b) development of a human peritoneal carcinoma xenograft in an animal model, and (c) determination of the utility of intraperitoneally (i.p.) administered MAb conjugates for carcinoma therapy.

该项目的总体目标是划定所涉及的参数 单克隆抗体的体内靶向。这些研究将涉及 确定抗体接种的最佳途径以及 抗体的形式。主要重点将放在以下药物的药代动力学 重组/嵌合单克隆抗体的血浆清除率及其应用 靶向肿瘤的能力 腹膜癌患者的一种治疗方法可能是 将放射性标记抗体直接输注到腹膜腔中 结合物。与静脉内MAb施用相比，该方法 可以提高每克肿瘤注射的MAb剂量的百分比， 骨髓中的放射性标记抗体较少， 对患者的毒性。该项目的第二个主要目标是 建立一个研究肿瘤免疫治疗的体内模型系统 在腹膜腔内。这些研究将包括（a）确定 与观察到的模式最相似的动物物种 在人中MA B从血液中清除，（B）人的发育 腹膜癌异种移植物在动物模型中的测定，和（c）测定 腹膜内（i. p.）施用的MAb缀合物用于 肿瘤治疗