ANTIBODY TARGETING TO PSMA IN PROSTATIC TUMORS

前列腺特异性膜抗原(PSMA)是前列腺上皮细胞的一种有效的细胞表面标志，在前列腺癌中表达增加，特别是在更具侵袭性的疾病中。我们已经制备了一组针对PSMA上存在的胞外表位的单抗。将进行研究，以确定它们在体内靶向治疗前列腺癌的潜在适宜性。抗原结合亲和力以及它们诱导ADCC和CDC细胞杀伤的内在能力将被确定。体外实验将检测~(125)I标记抗体与PSMA表达和非表达细胞的特异性，以及标记抗体在荷瘤小鼠体内的生物分布。基于这些结果，将进行初步测试，以评估90Y标记抗体在携带PSMA表达和非表达肿瘤的小鼠中的杀瘤活性。这一结果将为评估抗PSMA抗体靶向治疗药物在人类前列腺癌治疗中的潜力提供确凿的证据。建议的商业应用：1997年有209,900例新诊断的前列腺癌病例。这些患者中有许多已经或将发展为转移性癌症，对目前可用的治疗方法具有抵抗力。通过前列腺特异性膜抗原等标志物靶向治疗前列腺癌的抗体靶向应用应具有特异性，为晚期疾病的治疗提供新的手段。

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.