ANTIBODY TARGETING TO PSMA IN PROSTATIC TUMORS

前列腺肿瘤中针对 PSMA 的抗体

• 批准号: 2776431
• 负责人: Eric Holmes
• 金额: $ 10万
• 依托单位: NORTHWEST BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-18 至 2000-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2776431
• 关键词: antineoplastics; athymic mouse; drug design /synthesis /production; drug screening /evaluation; flow cytometry; immunocytochemistry; iodine; monoclonal antibody; neoplasm /cancer immunotherapy; neoplastic cell; pharmacokinetics; prostate neoplasms; prostate specific antigen; radiotracer; tumor antigens; western blottings; yttrium

Prostate-specific membrane antigen (PSMA) is an effective cell surface marker for prostatic epithelial cells and is increased in expression in prostatic cancer, particularly the more aggressive forms of the disease. We have prepared a panel of monoclonal antibodies for extracellular epitopes present on PSMA. Studies will be conducted to determine their potential suitability for in vivo targeting of therapeutics to prostatic tumors. Antigen binding affinity will be determined as will their intrinsic ability to elicit ADCC and CDC cell killing. Specificity of 125I-labeled antibody binding to PSMA expressing and non-expressing cells will be tested in vitro as well as biodistribution of labeled antibody in mice bearing tumors which are both expressors and non-expressors of PSMA. Based on these results, an initial test will be conducted to assess tumoricidal activity of a 90Y-labeled antibody in mice bearing PSMA expressing and non-expressing tumors. The results will provide definitive evidence to assess the potential of anti- PSMA antibody targeting of therapeutics in treatment of prostate cancer in humans. PROPOSED COMMERCIAL APPLICATIONS: There were 209,900 new cases of prostatic cancer diagnosed in 1997. Many of these patients have, or will develop, metastatic cancer which is resistant to presently available therapy. Application of antibody targeting of therapeutic agents to prostate cancer via markers such as prostate-specific membrane antigen should be specific and result in new means to treat advanced disease.

前列腺特异性膜抗原（PSMA）是前列腺上皮细胞的有效细胞表面标志物，并且在前列腺癌中表达增加，特别是该疾病的更具侵袭性的形式。我们已经制备了一组针对PSMA上存在的细胞外表位的单克隆抗体。 将进行研究以确定其用于前列腺肿瘤治疗剂的体内靶向的潜在适用性。 将测定抗原结合亲和力以及其引发ADCC和CDC细胞杀伤的内在能力。 将在体外测试125I标记的抗体与PSMA表达和非表达细胞结合的特异性以及标记抗体在携带肿瘤的小鼠中的生物分布，所述肿瘤是PSMA的表达者和非表达者。 基于这些结果，将进行初始测试以评估90Y标记的抗体在携带PSMA表达和非表达肿瘤的小鼠中的杀肿瘤活性。 结果将提供确定性证据来评估抗PSMA抗体靶向治疗剂在治疗人类前列腺癌中的潜力。建议的商业应用：1997年诊断出209，900例前列腺癌新病例。这些患者中的许多人患有或将发展对目前可用的疗法有抗性的转移性癌症。 通过标记物如前列腺特异性膜抗原将治疗剂的抗体靶向应用于前列腺癌应该是特异性的，并产生治疗晚期疾病的新手段。