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Previous studies have established the efficacy of irradiated cancer cells overexpressing GM-CSF or IL-21 as a vaccine. Here we examined whether the vaccine efficacy was greater when both factors were overexpressed together. MB49 bladder cancer cells were transfected with expression plasmid pT7TS encoding mouse GM-CSF and human IL-21, and then irradiated with 100 Gy at 4 days later. The cells (1×10 7 per animal) were injected subcutaneously into C57BL/6 mice at 0, 4, 8, and 12 days after inoculation with MB49 tumor xenografts. Control animals were injected with MB49 cells transfected with pT7TS encoding GM-CSF or IL-21 on its own. Tumor growth was monitored for 45 days and compared among the groups using repeated-measures ANOVA. Vaccination with irradiated MB49 cells did not affect xenograft growth. Vaccination with irradiated cells overexpressing GM-CSF or IL-21 alone significantly inhibited tumor growth and led to significantly more CD4 + CD8 + T cells and fewer CD4 + Foxp3 + T cells in the spleen and xenograft. These effects were even greater following vaccination with irradiated cells overexpressing both GM-CSF and IL-21. Irradiated bladder cancer cells overexpressing both GM-CSF and IL-21 are more effective than cells expressing either factor alone as a vaccine against bladder cancer., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

Objective: To develop a novel vaccine by immobilizing interleukin-21 (IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes (CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer., Methods: SA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine. C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine, soluble IL-21, GFP surface-modified MB49 cells, ethanol-fixed MB49 cells, or PBS. The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine., Results: IL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response (P<0.05). At the same effector-target (E:T) ratio, the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells (P<0.05)., Conclusion: With the protein-anchor technique, IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine. The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.