MONOCLONAL ANTIBODIES IN THE LYMPHATICES FOR DIAGNOSIS AND THERAPY OF TUMORS

淋巴管中的单克隆抗体用于肿瘤的诊断和治疗

• 批准号: 3939288
• 负责人: J N WEINSTEIN
• 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/3939288
• 关键词: breast neoplasms; drug vehicle; endoscopy; immunoconjugates; immunopharmacology; injection /infusion; liposomes; lung neoplasms; lymph node neoplasm; lymphoma; mathematical model; metastasis; monoclonal antibody; neoplasm /cancer classification /staging; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide diagnosis

We have defined a new approach to the use of monoclonal antibodies for diagnosis and therapy of tumor in lymph nodes: delivery to the nodes via lymphatic vessels after subcutaneous injection. To establish a firm pharmacokinetic basis for this approach, we first studied antibodies to normal cell types in the mouse lymph node. In vitro binding characteristics were combined with in vivo pharmacological parameters to develop a quantitative understanding of the delivery process using the SAAM computer modeling system. Armed with that background information, we then demonstrated and analyzed specific uptake in lymph node metastases of a guinea pit tumor. The approach was extended to include endoscopic techniques for reaching lymph node groups not accessible by subcutaneous injection. Imaging studies were followed up with attempts at therapy. For diagnosis of early metastatic tumor in the nodes, the lymphatic route can be expected to provide higher sensitivity, lower background, lower systemic toxicity, and faster localization than the intravenous route. It will also minimize the problem of cross-reactivity with antigen present on normal tissues. The experimental design of the guinea pig studies is currently being applied to detection of lymph node metastases in clinical stage II malignant melanoma and cutaneous T-cell lymphoma (CTCL). Similar protocols have been approved for breast carcinoma, Hodgkin's disease, small cell lung carcinoma, and non- small cell lung carcinoma. Our studies of CTCL have produced the most efficient antigen-specific imaging yet achieved in humans by any techniques. In vitro and animal studies are being continued both to optimize the clinical procedures and to explore basic functions of the immune system (see project #Z01CB08368-2 Selective Cytotoxicity in the Lymphatics). Our longer term aim is to understand the pharmacology of monoclonal antibodies and other ligands in order to develop criteria for rational molecular design of biological antitumor agents.

我们已经定义了一种新的方法来使用单克隆抗体 用于诊断和治疗淋巴结肿瘤的抗体： 皮下注射后通过淋巴管输送到淋巴结 注射 建立一个坚实的药代动力学基础， 方法，我们首先研究了正常细胞类型的抗体， 小鼠淋巴结。 体外结合特征如下： 结合体内药理学参数， 定量了解交付过程，使用 SAAM计算机建模系统。 有了这样的背景 信息，然后我们展示和分析了特定的摄取 在淋巴结转移的豚鼠窝肿瘤。 的方法 扩展到包括内窥镜技术， 不能通过皮下注射进入的节点组。 成像 研究的后续治疗尝试。 诊断 淋巴结中的早期转移性肿瘤，淋巴途径可以 期望提供更高的灵敏度、更低的背景、更低的 全身毒性，并且比静脉注射更快定位 路线 它还将最大限度地减少交叉反应的问题， 抗原存在于正常组织中。 豚鼠研究的实验设计目前是 应用于临床淋巴结转移的检测 II期恶性黑色素瘤和皮肤T细胞淋巴瘤 （CTCL）。 类似的方案已被批准用于乳腺癌 肺癌、霍奇金病、小细胞肺癌和非霍奇金淋巴瘤。 小细胞肺癌 我们对CTCL的研究已经产生了 迄今为止最有效的抗原特异性成像， 人类的任何技术。 体外和动物研究正在继续进行， 临床程序和探讨的基本功能， 免疫系统（参见项目#Z01CB08368-2选择性 淋巴管中的细胞毒性）。 我们的长远目标是 了解单克隆抗体和其他药物的药理学 配体，以制定合理的分子设计标准 生物抗肿瘤剂。