肿瘤疫苗TCL/CpG@GNP的构建及评价

打开文本图片集

中图分类号：R186.9，R730 文献标志码：A DOI：10.11958/20251525

Developmentand evaluation of the tumorvaccineTCL/CpG@GNP

CHEN Minchun，XUE Runqing， ZHAO Xin，ZHANG Meng，YE Dan， ZHANG Jingyi， ZHENG Jie Departmentofrmacy，Xi'anNo.3Hospital，theAfliated HospitalofNrthwest UnivesityXi'an78，Cina △Corresponding Author E-mail： 44682408@qq.com

Abstract： ObjectiveTo develop a tumor vaccine containing broad-spectrum neoantigen tumor cellysate （TCL）and CpGadjuvant，and to efectivelydeliver ittolymph nodedendriticcels.MethodsA novelpolymer，9- fluorenylmethoxycarbonyl-polyethylene glycol-glycocholicacid （Fmoc-PEG-GCA），was employed toencapsulate the TCL and CpG through π-π stacking，resulting in high-densitypolyethylene glycol-modified glycocholic acid-decorated micelles TCL/CpG @ GNP.The vaccine's drug loading，encapsulation efficiency，particle size，polydispersity index （PDI），zeta potential，morphology，stability，celularsafety，uptakecapability，immunestimulation effectsonbone marrw-derived dendriticcells （BMDCs）andinvivoanti-tumoreficacywere evaluated.ResultsThevaccineTCLandCpGdemonstrateda drug loading capacity of 6.26% and the encapsulation rate was 37.59% . The drug loading capacityof CpG was 7.O5%，and the encapsulation efficiency was 56.86% .The particle size measured （139.26±27.23）nm，with a PDI of 0.249±0.015 indicating favorable dispersionproperties.Thezeta potential wasrecordedat（-21.23±0.36）mV.The TCL/CpG@GNP vaccinedemonstratedgoodstability，cellsafetyanduptakeability，andcanpromote theactivationand maturationof BMDCs. In tumor-bearing mouse models，TCL/CpG @ GNPinhibited tumor growth， increased the proportion of T lymphocytes in peripheral blood，and elevated IFN- γ levels in spleen. ConclusionThe TCL/CpG@GNP tumor vaccine can effectively activate BMDCs and induce strong anti-tumor immune memory in a mouse lung cancer model.

Key Words： cancer vaccines; tumor cell lysates; CpG adjuvant; immunotherapy

肿瘤疫苗作为新型疗法，兼具治疗和预防作用，可激活免疫反应，但面临肿瘤特异性抗原覆盖率有限及树突状细胞（dendriticcell，DC）活化不足等问题，限制了其有效性和临床应用[1]。（剩余11828字）