| Malignancies are seriously imperilling human health. It is the second cause of mortality among all diseases and has an increasing tendency nowadays. Tumors escape from immune surveillance in many ways, such as expression defect of tumor antigen, abnormal expression of MHC molecules, deficiency of costimulatory molecules, immunosuppressive factors produced by malignancies, defect of antigen presenting function, et al. Therefore ,tumors can develop without limitation in human body. It is very difficult to treat malignancies because of the biological characteristic of tumor cells, which is aggression, metastasis and recurrence. The three main traditional therapies of malignancies are operation, radiotherapy and chemotherapy, these methods can not apply to the necessary of tumor therapy nowadays . So it is imperative to explore new and effective treatment for malignancies.Immunotherapy of tumors brings new hope today. The main aim of it is to eliminate tumors by way of induce and enhance active and specific immune response and improve tumor susceptibility to immune effect of the body.Cell immunity induced by T cells plays a critical role in anti tumor immunity. Superantigen SEA has great ability to active T cells, B7.1 molecules can provide the second signal for T cell activation and play a very important role during the process of antigen presenting and recognizing. We transduced the genes of staphylococcal enterotoxin A (SEA) and/or B7.1 into a murine hepotma cell line Hepal-6 both in vivo and in vitro and anti tumor immunological rejection indued was observed.In this study, we first explored the best condition for gene transfection mediated by cationic liposome DC-Choi, it laid a foundation for the following experiment. Then, SEA^ B7.1 genes were introduced into Hepal-6 cell line through liposome-mediated transfection .which were produced to betumor cell vaccine by MMC destroying. The vaccines had suppressive effect on mice tumors growth and survival time of mice prolonged. Immunization of mice with the vaccines led to a protective immunologic effect against wild type Hepal-6 cells. The results showed that tumor incidence decreased, latency period and survival time prolonged. The therapeutic group and preventive group, in which results of 51Cr release assay implied that the vaccines induced great CTL killing activity. At last, we did experiment in vivo. SEA and/or B7.1 genes were transduced into tumor by direct intratumor injection of plasmid DNA complexed to cationic liposome. The therapeutic effect to murine hepatoma was observed. The results showed that murine hepatoma grew slowly in SEA group, B7.1 group and SEA/B7.1 group, 30-40% murine hepatoma completely disappeared and the mice could live long without tumor in these groups. Significant prolonged survival time and decreasing tendency of tumor growth was seen in the SEA/B7.1 group. It implied that co-transfection of SEA gene with B7.1 gene had coordinated effect. The mechanism of anti hepatoma effect was that immunogenicity of hepatocellular cells enhanced and elicited specific CTL activity. Intratumoral transfection of SEA genes provided a way to solve the two difficult problems of SEA practical application. The toxin molecules were limited to the local region where transduced cells were situated and T cell tolerance was avoided. It decreased side effects in a great degree .SEA can initiate immunological reaction efficiently. B7.1 can assist T lymphocyte cells to recognize and kill the target cells. We transduced SEA, B7.1 genes respectively or together to murine hepotoma cells by liposome, SEA/B7.1 expressing system on Hepa 1-6 cells was constructed and the ability of murine hepatoma cells to induce immunologic rejection was increased. It shows inspiring results in the immunogene therapy of murine hepatoma.The results indicate that it is a prospect method to transduce objective genes to tumor cells targeted. It is safe, simple, quick and effective. It can produce both local and systemic immune responses and exploit a new way to therap...
|
PDF Full Text Request