MONOCLONAL ANTIBODIES FOR THE MANAGEMENT OF CANCER

用于治疗癌症的单克隆抗体

• 批准号: 6300384
• 负责人: DAVID V GOLD
• 金额: $ 29.24万
• 依托单位: CTR FOR MOLECULAR MEDICINE/IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-15 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6300384
• 关键词: antigen antibody reaction; antitumor antibody; athymic mouse; clinical research; diagnosis design /evaluation; human tissue; immunologic assay /test; laboratory mouse; monoclonal antibody; mucins; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; nonhuman therapy evaluation; pancreas neoplasms; protein structure; tissue /cell culture; tumor antigens

Cancer of the pancreas is the fourth and fifth leading cause of cancer deaths among men and women, respectively, in the United States today. Because of the location of the tumor and its silent growth, the overwhelming majority of patients present at a late stage of tumor growth when the disease is not responsive to traditional treatment methodologies. During the past few years of the currently active grant, we demonstrated that mAb-PAM4, reactive with a pancreatic cancer mucin, was able to distinguish pancreatic cancer from normal and inflamed pancreatic tissue; was able to target in a specific manner, and at high concentrations to experimental pancreatic tumors; and was able to cause growth inhibition and/or regression of experimental pancreatic tumors. These data provided rationale for the further development and in vivo clinical application of mAb-PAM4 to be performed as part of the current proposal. In addition to PAM4, mAb-Mu9, reactive with mucin, or a mucin-like molecule will be used for radioimmunodetection and therapy of colorectal cancer. In this Project we intend to examine the nature of the antigens to which these 2 antibodies are directed. We will examine the structure of the immunoreactive epitopes and study their relationship to other peptide and carbohydrate structures within mucin type glycoproteins. In addition, we intend to examine the interaction with antigen and metabolic fate of these antibodies at the molecular and cellular levels. These results will provide information to guide the further development of mAb-based technologies for detection and therapy of antigen positive cancer patients. With the knowledge developed from analyses of antigen structure and antigen:antibody interactions as well as feedback from preclinical and clinical targeting studies we will develop second generation antibodies for use against pancreatic cancer. Finally, we will examine the use of a PAM4-based enzyme immunoassay for the detection and quantitation of antigen in the blood of pancreatic cancer patients in the hope of providing earlier detection with potentially more effective therapeutic outcome. The specificity, sensitivity, and diagnostic accuracy will be determined. In a separate study we will examine the relationship of the blood antigen concentration with tumor burden, as a prelude to its use in monitoring treatment of patients.

胰腺癌是癌症的第四和第五主要原因 当今美国的男性和女人之间的死亡分别为死亡。 由于肿瘤的位置及其沉默生长， 绝大多数在肿瘤后期出现的患者 当疾病对传统治疗不反应时，生长 方法论。 在目前活跃赠款的过去几年中， 我们证明了用胰腺癌粘蛋白反应性的mab-pam4， 能够将胰腺癌与正常和发炎区分开 胰组织；能够以特定的方式靶向 实验性胰腺肿瘤的浓度；并能够造成 实验性胰腺肿瘤的生长抑制和/或回归。 这些数据为进一步发展和体内提供了理由 MAB-PAM4作为电流的一部分进行的临床应用 提议。 除了PAM4，MAB-MU9，粘蛋白反应性或A 粘蛋白样分子将用于放射免疫试验和治疗 结直肠癌。在这个项目中，我们打算检查性质 这两种抗体被定向的抗原。 我们将 检查免疫反应性表位的结构并研究其 与粘蛋白内其他肽和碳水化合物结构的关系 类型糖蛋白。 此外，我们打算检查相互作用 这些抗体的抗原和代谢命运在分子和 细胞水平。 这些结果将提供信息来指导 进一步开发基于mAb的检测和治疗技术 抗原阳性癌症患者。随着知识从 抗原结构和抗原的分析：抗体相互作用 作为临床前和临床靶向研究的反馈，我们将 开发用于抗胰腺癌的第二代抗体。 最后，我们将检查基于PAM4的酶免疫测定的使用 胰腺血液中抗原的检测和定量 癌症患者希望提供早期检测 潜在的更有效的治疗结果。 特异性， 灵敏度和诊断精度将得到确定。 在另一个 研究我们将检查血液抗原的关系 肿瘤负担的集中度，作为其用于监测的前奏 患者的治疗。