放射诱导性溶瘤腺病毒介导hSulf-1表达与肺癌131I-chTNT靶向治疗的协同增强作用研究

Advanced lung cancer is one of the most devastating malignant cancer and the incidence is occult. The traditional treatments such as radiotherapy and chemotherapy were not effective and reached a plateau.In recent years, combined modality therapy in the treatment of lung cancer achieved good effect. Listing of new targeted drugs bring the gospel to the patients with advanced lung cancer who were failed in first-line treatment.Although this single therapy has some effect, the clinical effect is still not satisfactory. Previously, we established a series of oncolytic viruses for gene therapy strategies in our technology platform of tumor-specific proliferous oncolytic virus. In order to apply this strategy to the comprehensive treatment of lung cancer, we construct a radiation-inducible oncolytic adenovirus Ad.eSurp-hSulf1.The radiation-inducible eSurp promoter regulates adenovirus targeting proliferation and tumor suppressor genes hSulf1 is carried , which play dual inhibitory effect of oncolytic virus proliferation and tumor suppressor gene expression. When131I-chTNT is incorporated into the treatment regimen, not only the antibody produces radioimmunotherapeutic effect, but the I131 radiation is able to activate the radiation-inducible promoter and further boost adenoviral proliferation and gene expression.This novel strategy that involved multiple, synergistic mechanisms, including oncolytic therapy, gene therapy and radioimmunotherapy, is demonstrated to exert an excellent anti-cancer outcome, which will be a promising approach in lung cancer treatment.

晚期肺癌发病隐匿、恶性程度高，传统的放化疗等治疗方式有效率已达到平台期。近年来，综合治疗方式在肺癌治疗中疗效显著。新的靶向治疗药物131I-chTNT的上市为广大一线治疗失败的晚期肺癌患者带来了福音，但单一的靶向治疗虽有疗效，临床效果仍不令人满意。我们在前期肿瘤特异性增殖的溶瘤病毒技术平台上，建立了一系列溶瘤病毒基因治疗策略。为了将这一策略应用到肺癌综合治疗中，我们构建了放射诱导增强型溶瘤腺病毒Ad.eSurp-hSulf1，以放射敏感的eSurp启动子调控腺病毒的靶向增殖，携带抑癌基因hSulf1，发挥病毒增殖溶瘤和基因表达抑瘤的双重疗效。与靶向治疗药物131I-chTNT联合应用时，除131I-chTNT单抗直接发挥的放射免疫作用以外，131I释放的射线激活溶瘤病毒放射诱导增强型启动子，进一步提高病毒增殖活性和基因表达水平，多重机制协同，发挥更优的抗癌效应，提高综合治疗的疗效和安全性。

晚期肺癌发病隐匿、恶性程度高，传统的放化疗等治疗方式有效率已达到平台期。近年来，综合治疗方式在肺癌治疗中疗效显著。新的靶向治疗药物131I-chTNT的上市为广大一线治疗失败的晚期肺癌患者带来了福音，但单一的靶向治疗虽有疗效，临床效果仍不令人满意。我们在前期肿瘤特异性增殖的溶瘤病毒技术平台上，建立了一系列溶瘤病毒基因治疗策略。为了将这一策略应用到肺癌综合治疗中，我们构建了放射诱导增强型溶瘤腺病毒Ad.eSurp-hSulf1，以放射敏感的eSurp启动子调控腺病毒的靶向增殖，携带抑癌基因hSulf1，发挥病毒增殖溶瘤和基因表达抑瘤的双重疗效。体内外实验证实，射线能够激活溶瘤病毒放射诱导增强型启动子，进一步提高病毒增殖活性和抑癌基因hSulf1表达水平，与靶向治疗药物131I-chTNT联合应用时，除放射诱导以外，131I-chTNT单抗直接发挥的免疫作用，多重机制协同，发挥更优的抗癌效应，提高综合治疗的疗效和安全性。

内容获取失败，请点击重试