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NY-ESO-1作为一种肿瘤抗原,具有较强的免疫抗原性,并且已成为肿瘤候选疫苗之一。但由于目前大多应用NY-ESO-1多肽以及蛋白质疫苗,其临床试验效果欠佳,亟需更为有效的NY-ESO-1抗原设计的肿瘤免疫治疗出现。该研究的目的是探索将NY-ESO-1与具有增强免疫效应的五种因子分别重组成嵌合蛋白抗原,使其更有效地被加工、转运和呈递,以期找到最佳的基因佐剂,增强NY-ESO-1作为肿瘤治疗性DNA疫苗的免疫效果。采用电脉冲体内细胞高效转入的方法对C57BL/6小鼠进行DNA免疫,发现用编码NY-ESO-1或连接有HSP70的嵌合体质粒免疫可诱导强烈的NY-ESO-1特异性Ig G1反应。NY-ESO-1连接泛素的质粒免疫小鼠主要诱导NY-ESO-1特异性Ig G2a反应,表明此基因佐剂诱导强的Th1免疫反应。与其他嵌合NY-ESO-1质粒免疫相比,NYESO-1连接泛素的质粒免疫小鼠,有效地保护小鼠对有NY-ESO-1表达的B16F10黑色素瘤细胞系的挑战作用,证明强的Th1免疫反应对预防和治疗肿瘤具有重要作用。去除调节性T细胞(regulatory T cells,Treg)可进一步增强泛素-NY-ESO-1嵌合DNA疫苗治疗黑色素瘤的作用。此外,Ub-NY-ESO-1质粒结合编码异源黑素瘤抗原GP100和TRP-2的质粒免疫可诱导对抗含有NY-ESO-1表达的B16F10黑色素瘤的协同抗肿瘤免疫疗效。该研究结果表明,编码泛素-NY-ESO-1嵌合抗原的质粒DNA疫苗或与编码其他相关黑色素瘤抗原的质粒的联合可能是有效的治疗黑色素瘤的疫苗。
As a tumor antigen, NY-ESO-1 has strong immunogenicity and has become one of the tumor candidate vaccines. However, due to the current application of NY-ESO-1 polypeptide and protein vaccine, its clinical trial is ineffective, and the more effective tumor immunotherapy designed by NY-ESO-1 antigen is urgently needed. The aim of this study was to explore the recombination of NY-ESO-1 and five factors with enhanced immune response into chimeric protein antigens to make them more efficiently processed, transported and presented in order to find the best gene adjuvant, Enhance the immune effect of NY-ESO-1 as a tumor therapeutic DNA vaccine. Immunization of C57BL / 6 mice with DNA was performed by electroporation in vivo and found that immunization with NY-ESO-1 or HSP70-linked chimeric plasmids induced strong NY-ESO-1 specific Ig G1 reaction. NY-ESO-1-linked ubiquitin plasmid-immunized mice mainly induced NY-ESO-1-specific Ig G2a responses, indicating that this gene adjuvant induces a strong Th1 immune response. Immunization of mice with NYESO-1-linked ubiquitin compared to other chimeric NY-ESO-1 plasmid vaccines effectively protected mice from challenging challenge with B16F10 melanoma cell line expressing NY-ESO-1, demonstrating A strong Th1 immune response plays an important role in the prevention and treatment of tumors. Removal of regulatory T cells (Tregs) further enhances the role of ubiquitin-NY-ESO-1 chimeric DNA vaccine in the treatment of melanoma. In addition, immunization with Ub-NY-ESO-1 plasmid in combination with plasmids encoding heterologous melanoma antigens GP100 and TRP-2 induced a synergistic anti-tumor immunotherapeutic effect against B16F10 melanoma containing NY-ESO-1 expression. The results of this study indicate that the combination of a plasmid DNA vaccine encoding a ubiquitin-NY-ESO-1 chimeric antigen or a plasmid encoding other related melanoma antigens may be an effective vaccine for the treatment of melanoma.