[1]盛 慧,赵智辉.个性化结直肠癌肿瘤疫苗的制备[J].南京师大学报(自然科学版),2022,(01):74-80.[doi:10.3969/j.issn.1001-4616.2022.01.011]
 Sheng Hui,Zhao Zhihui.Preparation of Personalized Colorectal Cancer Tumor Vaccine[J].Journal of Nanjing Normal University(Natural Science Edition),2022,(01):74-80.[doi:10.3969/j.issn.1001-4616.2022.01.011]





Preparation of Personalized Colorectal Cancer Tumor Vaccine
盛 慧赵智辉
(南京师范大学生命科学学院,生物化学与生物制品研究所,江苏省分子与医学生物技术重点实验室,江苏 南京 210023)
Sheng HuiZhao Zhihui
(School of Life sciences,Nanjing Normal University,Institute of Biochemistry and Biological Products,
colorectal cancertumor vaccinebioorthogonal reactiondendritic cells
目前,由于存在肿瘤特异性新抗原难鉴定以及无法将广谱肿瘤抗原通过激活性内吞受体途径递送给抗原提呈细胞等制约因素,使得肿瘤疫苗的临床疗效不佳,同时,肿瘤细胞表面抗原的高度唾液酸化修饰会导致免疫耐受. 所以,本研究尝试利用糖代谢掺入,使肿瘤抗原的唾液酸位点标记上正交基团-叠氮(-N3),同时将特定的激活性吞噬受体的配体标记上另一正交基团-炔烃,通过生物正交反应,制备肿瘤疫苗. 首先,利用分子生物学手段构建了重组质粒,再利用真核系统表达能靶向树突状细胞(dendritic cells,DCs)的重组蛋白mlgG1Fc. 接着,用含正交基团的化合物修饰吞噬受体的配体. 再者,通过代谢掺入途径将叠氮修饰的非天然糖标记到CT26.WT小鼠结直肠癌细胞抗原的糖基化修饰位点,制备N3-TAg. 最后,通过无铜点击反应将吞噬受体的配体与广谱肿瘤抗原缀合,制备个性化结直肠癌肿瘤疫苗. 结果证明,已成功利用真核系统表达出mlgG1Fc蛋白,并获得DIBO修饰的mlgG1Fc蛋白,将mlgG1Fc-DIBO与N3-TAg缀合,制备出个性化且靶向性DCs的结直肠癌肿瘤疫苗. 本研究在理论方法上为制备新型肿瘤疫苗提供了指导意义.
At present,due to the difficulty of identifying tumor-specific antigens and the inability to deliver broad-spectrum tumor antigens to antigen-presenting cells through the activating endocytic receptor pathway,the clinical therapeutic effect of existing tumor vaccines is not good.Meanwhile,the tumor cell antigens with highly sialylated modification can lead to immune tolerance. Therefore,this study tried to use metabolic incorporation to label the sialic acid of the tumor antigen with an orthogonal group-azide(-N3),and at the same time label the ligand of a specific activating phagocytic receptor with another orthogonal group-Alkynes,through bio-orthogonal reactions to prepare tumor vaccines. Firstly,construct and express the recombinant protein mlgG1Fc that can target dendritic cells(DCs),and then modify the ligands of the phagocytic receptor with compounds containing orthogonal groups. Secondly,the azide-modified unnatural sugars are used to label the glycosylation modification sites of CT26.WT colon cancer cell antigen through metabolic incorporation to prepare N3-TAg. Finally,the phagocytic receptor ligand is conjugated with a broad-spectrum tumor antigen through a copper-free click reaction to obtain a colorectal cancer tumor vaccine. The results proved that the use of genetic engineering methods to successfully express the mlgG1Fc protein,and obtain the DIBO-modified mlgG1Fc protein,and conjugate mlgG1Fc-DIBO with N3-TAg to prepare a targeted and stable colorectal cancer tumor vaccine. The research has laid the foundation for the preparation of new tumor vaccines in methodology.


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 Zhang Guoxiu,Zheng Chenchen,Zhao Zhihui.Biochemical Bridging of Ligand for Specific Activating PhagocyticReceptor and Broad-Spectrum Tumor Antigens[J].Journal of Nanjing Normal University(Natural Science Edition),2020,43(01):92.[doi:10.3969/j.issn.1001-4616.2020.02.015]
 Song Zhengwen,Zhao Zhihui.Construction of a Colon Cancer Tumor Vaccine Targeting Dendritic Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2020,43(01):112.[doi:10.3969/j.issn.1001-4616.2020.03.018]


通讯作者:赵智辉,博士,教授,研究方向:肿瘤免疫治疗. E-mail:Zhaozhihui1964_@aliyun.com
更新日期/Last Update: 1900-01-01