ANTI-CARCINOMA MONOCLONAL ANTIBODIES CLINICAL TRIALS

该项目涉及几种单抗的使用和建议使用 诊断和治疗临床试验中的抗体(单抗)。因此， 到目前为止，我们所有的合作临床试验都是用单抗进行的。 B72.3。这种单抗以前已经被证明具有不同的反应性。 与大多数正常成人组织相比，适用于一系列人类癌症。 到目前为止，已有1000多名患者接受了放射性标记的B72.3 在几个机构进行的肿瘤靶向研究，与 观察到约7080%的肿瘤靶向结果。 我们首先研究了放射性标记单抗B72.3免疫球蛋白在小鼠体内的给药情况。 结直肠癌患者。~(131)I-MAb B72.3的选择性定位 免疫球蛋白在生物分布研究中被证实，其中 将每克肿瘤的单抗注射剂量与 正常组织，从而提供相对放射定位化指数(RI) 每一处病变。在肿瘤病变中，70%的RI至少为3(即3 每克摄取量是正常组织的三倍)。我们还进行了 确定腹膜腔给药的可行性的研究 用于肿瘤定位的放射性标记B72.3(通过伽马扫描和 直接分析活组织标本)。研究了几名患者 CT扫描和X线检查肿瘤均为阴性，但呈阳性 用于通过伽马扫描进行肿瘤定位。活组织检查的直接分析 癌组织和正常组织标本的比例高达70：1 用于肿瘤单抗定位与正常组织的比较。 一项涉及腹腔注射(131)的I期治疗试验 卵巢癌和结直肠癌患者血清中I-B72.3免疫球蛋白检测 腹膜腔手术正在进行中。重组/嵌合单抗的应用 也已经开始，其他单抗-同位素偶联物也在计划中。

This project involves the use and the proposed use of several monoclonal antibodies (MAbs) in both diagnostic and therapeutic clinical trials. Thus far, all our collaborative clinical trials have been conducted with MAb B72.3. This MAb has been previously shown to have differential reactivity for a range of human carcinomas as compared to most normal adult tissues. To date, over 1,000 patients have been administered radiolabeled B72.3 in tumor-targeting studies carried out in several institutions, with similar findings of approximately 7080% tumor targeting observed. We first investigated the administration of radiolabeled MAb B72.3 IgG in colorectal cancer patients. The selective localization of (131)I-MAb B72.3 IgG was demonstrated in biodistribution studies in which the percentage of injected dose of MAb per gram of each tumor was compared with that of the normal tissues, thus providing a relative radiolocalization index (RI) for each lesion. Of the tumor lesions, 70% had an RI of at least 3 (i.e., 3 times greater uptake per gram than normal tissues). We have also conducted studies to determine the feasibility of intraperitoneal administration of radiolabeled B72.3 for tumor localization (via both gamma scanning and direct analyses of biopsy specimens). Several patients studied were negative for tumor detection by both CT scan and X-ray but were positive for tumor localization via gamma scanning. Direct analyses of biopsy specimens of carcinoma and normal tissues demonstrated ratios ofup to 70:1 for tumor MAb localization versus normal tissues. A phase I therapy trial involving intraperitoneal administrationof (131) I-B72.3 IgG in patients with ovarian or colorectal carcinoma confined to the peritoneal cavity is in progress. The use of recombinant/chimeric MAbs has also begun and other MAb-isotope conjugates are planned.