1. 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.
- Author
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Peng J, Ye L, Li T, Zhu Q, Guo J, Xiao K, and Wei Y
- Subjects
- Animals, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes radiation effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Proliferation radiation effects, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic radiation effects, Heterografts, Humans, Mice, Urinary Bladder pathology, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms immunology, Urinary Bladder Neoplasms radiotherapy, Urothelium pathology, Cancer Vaccines pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Interleukins genetics, Urinary Bladder Neoplasms prevention & control
- Abstract
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.- Published
- 2019
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