IMMUNOTOXIN THERAPY FOR PROSTATIC CARCINOMAS

PSMA是前列腺特异性膜结合蛋白抗原， 由鼠单克隆抗体7E11.C5定义。 PSMA高度 在前列腺癌中表达，特别是在更耐药的 以及随着疾病进展而出现的侵袭性细胞克隆。 7E11.C5抗体已成功应用于免疫闪烁成像 以帮助定位转移性疾病。 由于高 该抗原的组织特异性和适当的 单克隆抗体，拟议的实验旨在测试 免疫毒素疗法作为控制疾病的手段的潜力。 实验将利用组织培养系统和动物模型 评估今后扩大这一模式的潜力 research. 这些实验将测试免疫毒素对细胞的杀伤作用， 表达和不表达人前列腺细胞系。 基于这些 结果，INCaP细胞接种于裸小鼠的免疫毒素攻击 将进行测试，沿着分析免疫毒素的作用 给药对裸小鼠中生长的INCaP肿瘤的影响。 的结果 这些实验将提供有关 基于PSMA抗原的免疫毒素用于前列腺的未来价值 临床环境中的癌症治疗 拟议的商业应用：免疫毒素治疗代表了 潜在的有效的治疗前列腺癌的方式。 这种基于PSMA抗原和适当抗体的方法， 考虑到抗原的组织特异性及其 随着进展，侵袭性细胞克隆增加。显著 基于此，在临床应用中存在商业潜力 技术.

PSMA is a prostate-specific membrane bound protein antigen which is defined by the murine monoclonal antibody 7E11.C5. PSMA is highly expressed in prostatic carcinomas, particularly in the more resistant and aggressive clones of cells which appear as the disease progresses. The 7E11.C5 antibody has been successfully applied to immunoscintigraphy to aid in the localizing of metastatic disease. Because of the high tissue specificity of this antigen and the existence of appropriate monoclonal antibodies, the proposed experiments are intended to test the potential of immunotoxin therapy as a means for controlling the disease. Experiments will utilize both tissue culture systems and animal models to assess the potential of this modality to be expanded upon in future research. These experiments will test cell killing by immunotoxin in expressing and non-expressing human prostate cell lines. Based on these results, immunotoxin challenge of INCaP cells inoculated into nude mice will be tested, along with an analysis of the effect of immunotoxin administration on growing INCaP tumors in nude mice. The results of these experiments will provide definitive evidence relating to the future value of immunotoxin use based on the PSMA antigen for prostate cancer treatment in a clinical setting. PROPOSED COMMERCIAL APPLICATION: Immunotoxin therapy represents a potentially effective modality for treatment of prostatic carcinoma. This approach based upon the PSMA antigen and appropriate antibodies is very attractive given the tissue specificity of the antigen and its increase in aggressive cell clones as progression occurs. Significant commercial potential exists in clinical applications based upon this technology.