IMMUNOLIPOSOME MEDIATED GENE THERAPY FOR PROSTATE CANCER

描述：(改编自申请者摘要)晚期前列腺癌 倾向于对标准的化疗药物相对耐受，而这 化疗耐药与功能性P53的缺失有关。我们的初步数据 提示癌细胞可通过P53对化疗增敏 使用肿瘤靶向脂质体递送系统进行置换。在这 建议，一种来源于单抗的重组单链片段(ScFv) 抗体将被用来靶向已知的转铁蛋白受体 在各种肿瘤类型的细胞表面都有升高，包括 前列腺。在第一阶段，免疫脂质体的脂质成分将为 优化、表达和纯化单链抗体，并对递送系统进行测试 在培养中使用人类前列腺癌细胞。P53基因的影响 这些细胞对多种常用药物敏感性的恢复 将对化疗药物进行评估。最后，使用裸鼠模型 人前列腺癌异种移植瘤免疫脂质体的能力 靶向原发和转移性前列腺癌将进行测试。这个 该项目的较长期目标是开发和营销更多 免疫脂质体介导的P53基因对前列腺癌的有效治疗 治疗加化疗。 建议的商业应用：不可用

DESCRIPTION: (Adapted from the applicant's abstract) Advanced prostate cancer tends to be relatively refractory to standard chemotherapeutic agents, and this chemoresistance correlates with a lack of functional p53. Our preliminary data indicate that cancer cells can be sensitized to chemotherapy via p53 replacement using a tumor-targeting liposomal delivery system. In this proposal, a recombinant single-chain fragment (scFv) derived from a monoclonal antibody will be employed to target the transferrin receptor that is known to be elevated on the surface of cells from a variety of tumor types including prostate. In Phase I, the lipid composition of the immunoliposome will be optimized, the scFv expressed and purified, and the delivery system tested using human prostate cancer cells in culture. The impact of p53 gene restoration on the sensitivity of these cells to a variety of commonly used chemotherapeutic agents will be assessed. Finally, using a nude mouse model involving human prostate cancer xenografts, the ability of the immunoliposomes to target primary and metastatic prostate tumors will be tested. The longer-term aim of this project is development and marketing of a more effective treatment for prostate cancer using immunoliposome-mediated p53 gene therapy plus chemotherapy. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE