MONOCLONAL ANTIBODIES IN THE LYMPHATICES FOR DIAGNOSIS AND THERAPY OF TUMORS

我们已经定义了一种使用单克隆抗体的新方法， 淋巴结内肿瘤的诊断和治疗：经淋巴结转移 皮下注射后的淋巴管。 的牢固 为了建立这种方法的药代动力学基础，我们首先研究了 小鼠淋巴结中的正常细胞类型。 体外结合 特征与体内药理学参数相结合， 使用SAAM对交付过程进行量化理解 计算机模拟系统 有了这些背景信息，我们 证明并分析了淋巴结转移的特异性摄取， 豚鼠肿瘤 该方法扩展到包括内窥镜 用于到达皮下组织无法到达的淋巴结组的技术 注射 影像学检查后进行治疗尝试。 为 诊断早期转移性肿瘤的淋巴结，淋巴途径， 预期提供更高的灵敏度、更低的背景、更低的系统性 毒性和比静脉途径更快的定位。 它还将 最大限度地减少与存在于正常细胞上的抗原的交叉反应性问题， 组织中 豚鼠研究的实验设计目前正在 适用于临床II期淋巴结转移的检测 恶性黑色素瘤和皮肤T细胞淋巴瘤（CTCL）。 类似协议 已经被批准用于乳腺癌，霍奇金病，小细胞肺癌 癌和非小细胞肺癌。 我们对CTCL的研究 产生了迄今为止在人类中最有效的抗原特异性成像， 任何技术。 体外和动物研究正在继续进行，以优化 临床程序和探索免疫系统的基本功能。 我们的长期目标是了解单克隆抗体的药理学 抗体和其他配体，以制定合理的标准， 生物抗肿瘤剂的分子设计。

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 pig 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. 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.