PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
树突状细胞(DC)疫苗在肿瘤免疫治疗中的疗效常因抗原交叉呈递(XPT)效率低下导致的免疫原性较弱而受到限制。
英文原题:Effects of a Dendritic Cell Vaccine Loaded With Whole Tumor Antigen on Bladder Cancer Model in hu-PBL-SCID Mice.
这些结果支持DC疫苗作为膀胱癌一种有前景的免疫治疗策略的潜力。
本研究旨在建立严重联合免疫缺陷(SCID)小鼠的人源化免疫系统模型,评估树突状细胞(DC)表型,并评价基于DC的疫苗在膀胱癌模型中的治疗疗效。通过注射T24细胞在SCID小鼠中诱导膀胱癌,随后接种人外周血白细胞(hu-PBL)以重建人免疫系统。通过培养hu-PBL 5天在体外生成DC,并在第8天使其成熟。DC疫苗通过与全肿瘤抗原共培养制备,该抗原通过冻融T24细胞纯化。通过在T24细胞注射后第5周和第6周向SCID小鼠给予疫苗,评估DC疫苗的治疗疗效。评估了免疫重建、DC表型、肿瘤重量和基质金属蛋白酶-7(MMP-7)mRNA表达。所有SCID小鼠均成功发生膀胱癌,确诊为尿路上皮癌。接种hu-PBL后,第5周在小鼠血清中可检测到人IgG,脾脏重量随时间增加,表明人免疫系统成功重建。DC的表型分析显示成熟标志物高表达,包括CD1a(78.07% ± 9.43%)、CD80(60.11% ± 20.50%)和CD83(46.82% ± 14.15%),表明DC功能成熟。DC疫苗的治疗干预显著降低了肿瘤重量和MMP-7 mRNA表达,具有统计学意义(肿瘤重量p = 0.0004,MMP-7 p = 0.0008)。本研究成功建立了SCID小鼠的人源化免疫系统模型,并证明基于DC的疫苗在膀胱癌模型中有效抑制肿瘤生长。这些结果支持DC疫苗作为膀胱癌有前景的免疫治疗策略的潜力。
The aim of this study was to establish a humanized immune system model in severe combined immunodeficient (SCID) mice, assess dendritic cell (DC) phenotype, and evaluate the therapeutic efficacy of a DC-based vaccine in a bladder cancer model. Bladder cancer was induced in SCID mice by injection of T24 cells, followed by human peripheral blood leukocyte (hu-PBL) inoculation to reconstitute the human immune system. DCs were generated in vitro by culturing hu-PBL for 5 days and matured on the eighth day. The DC vaccine was produced by coculturing with whole tumor antigen which was purified through freezing and melting T24 cells. The therapeutic efficacy of a DC vaccine was evaluated by administering the vaccine to SCID mice at Weeks 5 and 6 after T24 cell injection. Immune reconstitution, phenotype of DCs, tumor weight, and matrix metalloproteinase-7 (MMP-7) mRNA expression were assessed. All SCID mice successfully developed bladder cancer, confirmed as urothelial carcinoma. After hu-PBL inoculation, human IgG was detectable in mouse serum at Week 5, and spleen weight increased over time, indicating successful human immune system reconstitution. Phenotypic analysis of DCs showed high expression of maturation markers, including CD1a (78.07% ± 9.43%), CD80 (60.11% ± 20.50%), and CD83 (46.82% ± 14.15%), indicating functional and mature DCs. Therapeutic intervention with the DC vaccine significantly reduced tumor weight and MMP-7 mRNA expression, with statistical significance (p = 0.0004 for tumor weight and p = 0.0008 for MMP-7). This study successfully established a humanized immune system model in SCID mice and demonstrated that a DC-based vaccine effectively inhibits tumor growth in a bladder cancer model. These results support the potential of DC vaccines as a promising immunotherapeutic strategy for bladder cancer.
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