Effects of a Dendritic Cell Vaccine Loaded With Whole Tumor Antigen on Bladder Cancer Model in hu-PBL-SCID Mice

Abstract

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.