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

鼠源性单克隆抗体已被施用至 大量的癌症患者。 总的来说这些 抗体能够定位于肿瘤部位，但 并没有带来有意义的肿瘤反应。 的最终用途 这种抗体将受到人类发育的限制 抗小鼠抗体应答。 这种抗体不仅会导致 一些毒性作用，但已被证明会影响 抗体的生物分布和施用的抗体的能力 抗体到达肿瘤部位。 进行该实验 使用最近开发的人类单克隆抗体， 克服了与鼠相关的抗原性问题， 克隆抗体 我们已经给予抗体16.88 或28A32至26名患者，并且没有注意到 在任何实施方案中，所施用的人单克隆抗体的抗体 病人 3名患者有预先存在的抗28A32抗体， 其中一种抗体滴度有所增加， 患者 26例中有20例获得了肿瘤的阳性图像 患者;其他6例未获得图像的原因 患者不详，但在一名患者中， 用抗体28A32获得，所述抗体28A32是具有 发现了与28A32相似的反应性。推测该抗体 作为"阻断抗体"， 标记的抗体到达肿瘤靶点。 的能力 这些抗体定位于肿瘤部位， 癌症患者的免疫原性表明， 用于将治疗剂量的放射性核素输送到 肿瘤

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.