EXPERIMENTAL IMMUNOTHERAPY OF CANCER

该项目的总体目标是设计和测试各种模式 以及抗体介导的癌症同位素治疗的组合。这个 实验模型为癌胚抗原(CEA)和 产生GW-39人结肠癌的结肠特异性抗原-p(CSAP) 异种移植到仓鼠体内。131I、铜、安慰剂的疗效观察 32-P标记亲和纯化的抗CEA和cSAP山羊抗体 与针对小鼠的单抗进行比较 这两个肿瘤标志物。不同表位的单抗 这些抗体的特异性和亲和力以及确定的混合物 针对同一抗原上的不同表位或针对不同的表位 将对抗原进行检查，以确定其治疗优势。饱和度和 抗GW-39肿瘤单抗的结合特性将是 与山羊抗体相比。放射性抗体要么是 完整或其碎片，将在不同的剂量和治疗中使用 影响GW-39肿瘤生长行为的时间表 确定最佳治疗条件。肿瘤与肿瘤的关系 治疗开始时的大小对治疗效果也会有影响 已评估。这些研究的结果将提供对 杂交瘤来源的单抗的相对治疗优势 抗体优于常规抗体制剂，并定义 影响其疗效的单抗特性 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.