EVAL. OF HUMAN ANTICOLORECTAL CARCINOMA MOAB IN PATS. WITH DISSEM. COLON CA

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• 批准号: 3916680
• 负责人: R G STEIS
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 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/3916680
• 关键词: antibody formation; antitumor antibody; blocking antibody; carcinoma; human subject; human therapy evaluation; human tissue; immunogenetics; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer remission /regression; radionuclide imaging /scanning; radiotracer

Monoclonal antibodies of murine origin have been administered to large numbers of patients with cancer. In general, these antibodies have been able to localize to sites of tumor but have not brought about meaningful tumor responses. The ultimate use of such antibodies will be limited by the development of human antimouse antibody responses. Such antibodies may not only cause some toxic effects but have been shown to influence the biodistribution of antibodies and the ability of the administered antibody to reach the sites of tumor. This study was undertaken to use recently developed human monoclonal antibodies to hopefully overcome the problem of antigenicity associated with murine monoclonal antibodies. We have administered either antibody 16.88 or 28A32 to 26 patients and have not noted the development of antibodies to the administered human monoclonal antibody in any patient. Three patients had pre-existing anti-28A32 antibodies, and the titer of antibody increased somewhat in one of these patients. Positive images of tumors were obtained in 20 of the 26 patients; the reason why images were not obtained in the other six patients is unknown, but in one patient in whom an image was not obtained with antibody 28A32, an endogenous antibody with reactivity similar to 28A32 was found. Presumably this antibody acted as a "blocking antibody" and prevented the administered labeled antibody from reaching the tumor target. The ability of these antibodies to localize to sites of tumor and their lack of immunogenicity in patients with cancer suggest that they might be used to deliver therapeutic doses of radionuclides to sites of tumor.

鼠源性的单抗已经被用来治疗 大量的癌症患者。一般而言，这些 抗体已经能够定位于肿瘤部位，但 没有带来有意义的肿瘤反应。的最终用法 这种抗体将受到人类发育的限制 抗小鼠抗体反应。这种抗体不仅可能导致 一些毒性作用，但已被证明影响 抗体的生物分布与接种者的能力 抗体到达肿瘤部位。这项研究是在 利用新近研制的人类单抗有望 克服与小鼠相关的抗原性问题 单克隆抗体。我们已经注射了两种抗体中的任何一种 或28A32到26名患者，并且没有注意到 在任何一种情况下注射的人单抗抗体 有耐心的。三名患者已有抗28A32抗体， 其中一个的抗体效价有所增加。 病人。26例中有20例肿瘤显影阳性。 患者；其他六个患者没有获得图像的原因 患者未知，但有一名患者的图像不是 用抗体28A32获得的内源性抗体 反应活性与28A32相似。据推测，这种抗体 起到“封闭抗体”的作用，防止给药 标记的抗体不能到达肿瘤靶点。的能力 这些抗体定位于肿瘤部位，而它们缺乏 癌症患者的免疫原性表明他们可能是 用于将治疗性剂量的放射性核素输送到 肿瘤。