【摘 要】
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Purpose: To improve the efficacy of adoptive immunotherapy,we aimed to develop a novel therapy approach to increase the concentration of tumor antigen-specific CTLs in tumor tissues and improve their
【机 构】
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National Center for International Research of Biological Targeting Diagnosis and Therapy,Guangxi Med
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Purpose: To improve the efficacy of adoptive immunotherapy,we aimed to develop a novel therapy approach to increase the concentration of tumor antigen-specific CTLs in tumor tissues and improve their anti-tumor activities.Method: Chitosan nanoparticles were prepared using the ion template method,then folate and carbodiimide were then combined in a beaker and mixed in the dark using a magnetic stirrer for 1 h.The diluted hIP-10 plasmid and folate-modified chitosan nanoparticles were mixed quickly obtain the folate-modified chitosan nanoparticles coating the human IP-10 gene(FA-CS-hIP-10).Induction of pMAGE-A1278-286 specific CD8+ CTLs.Establishment of Hepatocellular Carcinoma in Nude Mice.Evaluation of anti-tumor treatments of the combination of FA-CS-hIP-10 and pMAGE-A1278–286 specific CD8+ CTLs.Result: The characteristic features of the FA-CS-hIP-10 included good dispensability,uniform size,round shape with about 266.7 nm diameter,and a positively charged surface.The combination of FA-CS-hIP-10 and pMAGE-A1278-286 specific CD8+ CTLs efficiently increased the secretion of IFN-γ,inhibited tumor growth and extended the survival of nude mice with subcutaneously transplanted human hepatocellular carcinoma.Conclusion: In this study,we developed FA-CS-hIP-10,which specifically bound to the folate receptors on hepatoma cells and promoted the expression of IP-10 to improve the activity of pMAGE-A1278-286 specific CTLs.Our results demonstrated that the mechanism of this novel therapy approach was involved in the inhibition of angiogenesis,inhibition of proliferation,and promotion of apoptosis of tumor cells.Our study provided a potentially novel approach for the treatment of human hepatocellular carcinoma by improving the activity of tumor antigen-specific CTLs.
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