Irradiated Bladder Cancer Cells Expressing both GM-CSF and IL-21 versus Either GM-CSF or IL-21 Alone as Tumor Vaccine in a Mouse Xenograft Model

Abstract EN

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 (1×107 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.