CLINICAL TRIALS WITH RADIOLABELED ANTIBODIES

放射性标记抗体的临床试验

• 批准号: 3939339
• 负责人: J SCHLOM
• 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/3939339
• 关键词: carcinoma; complement; human subject; human tissue; immunoconjugates; immunoglobulin G; immunoglobulins; immunotherapy; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunology; neoplasm /cancer radionuclide diagnosis; nuclear medicine; radionuclide imaging /scanning; radiotracer; rectum neoplasms; toxin; tumor antigens

Accurate detection and anatomic localization of both primary and metastatic lesions remains one of the major problems in the management of most human carcinomas. We have recently initiated clinical trials at the NIH Clinical Center to detect and localize colorectal carcinoma lesions using radiolabeled monoclonal antibody (MAb) B72.3. Parameters that are being systematically investigated concerning both the efficiency of MAb localization and the efficiency of gamma scanning of carcinoma lesions include: (a) effect of MAb dose and specific activity of radionuclide coupled MAb; (b) comparison of the use of intact IgG, F(ab')2, and Fab'; (c) choice of radionuclide; (d) route of inoculation; (e) size, location, and other inherent properties of the tumor mass such as antigen content; (f) the presence of circulating antigen; (g) the presence and/or absence of human anti-murine Ig antibodies; (h) metabolism of MAb and fragments; (i) combinations of MAbs. It is hoped that these studies will also aid in establishing a rational basis for the subsequent therapeutic use of a particular MAb, either coupled to toxins, via effector cell-mediated or complement-mediated mechanisms, or using MAbs radiolabeled with one of a variety of isotopes. This latter goal can be accomplished by direct analyses of biopsy material (both tumor and normal tissues) from patients receiving radiolabeled MAb to define the "radiolocalization index" or potential "therapeutic index" (i.e., the ratio of the amount of MAb bound (via cpm) per gram of tumor tissue to that bound per gram of normal tissues).

准确检测和解剖定位原发灶和 转移性病变仍然是乳腺癌的主要问题之一。 大多数人类癌症的管理。我们最近做了 在NIH临床中心启动临床试验，以检测和 应用放射性标记技术定位结直肠癌病变 单抗(MAb)B72.3。参数正在被 系统地调查了两个方面的效率 单抗定位与伽玛刀扫描效率 癌损害包括：(A)单抗剂量和特异性的影响 放射性核素偶联单抗的活度；(B)使用的比较 完整的IgG、F(ab‘)2和Fab’；(C)放射性核素的选择；(D)路线 关于接种；(E)大小、位置和其他固有特性 肿瘤肿块，如抗原含量；(F)是否存在 循环抗原；(G)人的存在或不存在 抗鼠Ig抗体；(H)单抗和片段的代谢； (I)单抗的组合。希望这些研究也将 帮助为随后的治疗建立合理的基础 使用特定的单抗，通过效应器与毒素偶联 细胞介导或补体介导的机制，或使用 用多种同位素中的一种放射性标记的单抗。后者 通过直接分析活组织检查材料可以实现这一目标 (包括肿瘤组织和正常组织) 用放射性标记的单抗来定义“放射定位指数”或 潜在的“治疗指数”(即单抗的量的比率 每克肿瘤组织与每克肿瘤组织的结合(通过CPM) 正常组织)。