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The experimental study of lung carcinoma vaccine modified by human B7-1 and IFN-γ genes

机译:人B7-1和IFN-γ基因修饰的肺癌疫苗的实验研究

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With the advance of immunology, immunogene therapy is becoming a possible therapeutic alternative to advanced cancer. The aim of tumor immunogene therapy is to enhance the immune response to tumors. Evidence suggests that CD80 (B7-1) and Interferon-gamma (IFN-γ) play important roles in antitumor immunity induced by T lymphocyte. To study the antitumor immune effects of lung carcinoma vaccine modified with human B7-1 and IFN-γ genes, we constructed the bicistronic retroviral vector pLXSN, encoding human B7-1 and IFN-g. In vitro, the primary lung carcinoma cells were transduced with the retroviral vector and prepared as a vaccine. Then autologous lymphocytes were irritated with the lung carcinoma cells for competition inhibitory cytotoxic testing. The tumor-specific cytotoxic activity was greatly enhanced by the double gene---modified vaccine. In vivo, the tumorigenicity of the double gene---modified lung cell line A-549/B7-1·IFN-γ was evaluated in a human immune reconstituted SCID mice (hu-PBL-SCID) model. The double-gene modification markedly decreases tumor genecity. Together, the results suggest that combining B7-1 and IFN-γ could be a useful therapeutic approach in lung cancer.
机译:随着免疫学的发展,免疫基因治疗正成为晚期癌症的一种可能的治疗选择。肿瘤免疫基因治疗的目的是增强对肿瘤的免疫反应。有证据表明,CD80(B7-1)和γ-干扰素(IFN-γ)在T淋巴细胞诱导的抗肿瘤免疫中起重要作用。为了研究用人B7-1和IFN-γ基因修饰的肺癌疫苗的抗肿瘤免疫作用,我们构建了编码人B7-1和IFN-g的双顺反子逆转录病毒载体pLXSN。在体外,用逆转录病毒载体转导原代肺癌细胞,并制成疫苗。然后用肺癌细胞刺激自体淋巴细胞进行竞争抑制性细胞毒性试验。双重基因修饰的疫苗大大增强了肿瘤特异性的细胞毒活性。在体内,在人类免疫重建的SCID小鼠(hu-PBL-SCID)模型中评估了双基因修饰的肺细胞系A-549 / B7-1·IFN-γ的致瘤性。双基因修饰显着降低了肿瘤的发生率。在一起,结果表明结合B7-1和IFN-γ可能是一种有用的肺癌治疗方法。

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