EXPERIMENTAL IMMUNOTHERAPY OF CANCER

该项目的总体目标是设计和测试各种模式 和抗体介导的同位素治疗癌症的组合。 的 使用的实验模型是癌胚抗原（CEA）， 产生结肠特异性抗原p（CSAp）的GW-39人结肠癌 异种移植到仓鼠体内 131-I、64-Cu、 32-P标记的亲和纯化的山羊抗CEA和CSAp抗体将 与鼠单克隆抗体相比， 这两种肿瘤标志物 不同表位的单克隆抗体 特异性和亲和力以及这些抗体的确定混合物 针对相同抗原上的不同表位或针对不同的 将检查抗原的治疗优势。 饱和度和 单克隆抗体与GW-39肿瘤的结合特性将是 与山羊抗体相比。 放射性抗体， 完整或其片段将以不同剂量和治疗使用 时间表来影响GW-39肿瘤的生长行为， 确定治疗的最佳条件。 肿瘤的关系 治疗开始时的大小对治疗效果的影响也将是 评估。 这些研究的结果将有助于了解 杂交瘤衍生单克隆的相对治疗优势 与常规抗体制剂相比， 单克隆抗体的特性影响其功效， 用于最终用于癌症患者的同位素治疗剂。

The overall objective of this project is to devise and test various modes and combinations of antibody-mediated isotopic therapy of cancer. The experimental model to be used is the carcinoembryonic antigen (CEA) and colon-specific antigen-p (CSAp) producing GW-39 human colonic carcinoma xenografted in hamsters. The therapeutic efficacy of 131-I, 64-Cu, and 32-P labeled affinity-purified, goat antibodies against CEA and CSAp will be compared with that of murine monoclonal antibodies directed against these two tumor markers. Monoclonal antibodies with different epitope specificity and affinityas well as defined mixtures of these antibodies against different epitopes on the same antigen or against different antigens will be examined for therapeutic advantage. Saturation and binding characteristics of monoclonal antibodies to GW-39 tumors will be compared to that of goat antibodies. The radioactive antibodies, either intact or fragments thereof, will be used in different dose and treatment schedules to affect the growth behavior of GW-39 tumors in order to determine the optimal conditions for therapy. The relationship of tumor size at the onset of therapy to therapeutic effectiveness also will be evaluated. The results of these studies will provide an understanding of the relative therapeutic advantage of hybridoma-derived monoclonal antibodies over conventional antibody preparations, and a definition of monoclonal antibody characteristics that influence their efficacy as isotopic therapeutic agents for eventual use in cancer patients.