The Experimental Study of Lung Carcinoma Vaccine Modified by Human B7-1 and IFN-gamma Genes

摘要

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-gamma) 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-gamma 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-gamma 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-gamma could be a useful therapeutic approach in lung cancer.