Journal article
Anti-Interleukin-10R1 Monoclonal Antibody Enhances Bacillus Calmette-Guerin Induced T-Helper Type 1 Immune Responses and Antitumor Immunity in a Mouse Orthotopic Model of Bladder Cancer
The Journal of urology, Vol.187(6), pp.2228-2235
06/01/2012
DOI: 10.1016/j.juro.2012.01.030
PMID: 22503050
Abstract
Purpose: Properinduction of the T-helper type 1 immune response is required for effective bacillus Calmette-Guerin immunotherapy for bladder cancer. Interleukin-10 down-regulates the T-helper 1 response and is associated with bacillus Calmette-Guerin failure. We investigated whether blocking interleukin-10 receptor 1 would enhance the bacillus Calmette-Guerin induced T-helper type 1 immune response and anti-bladder cancer immunity in a mouse model.
Materials and Methods: Splenocytes were incubated with bacillus Calmette-Guerin or bacillus Calmette-Guerin plus control IgG1, anti-interleukin-10 receptor 1 mAb or anti-interleukin-10 neutralizing mAb, followed by enzyme-linked immunosorbent assay of interferon-gamma production. Bladder RNA was extracted after intravesical bacillus Calmette-Guerin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb and analyzed by reverse transcriptase and/or quantitative polymerase chain reaction. Urine was collected and analyzed by enzyme-linked immunosorbent assay. Mice bearing a luciferase expressing MB49 orthotopic tumor were treated with intravesical bacillus Calmette-Guerin plus intraperitoneal IgG1 or anti-interleukin-10 receptor 1 mAb. Tumor response was assessed by bioluminescent imaging and bladder weight measurement.
Results: Bacillus Calmette-Guerin plus anti-interleukin-10R1 mAb induced significantly higher interferon-gamma production by splenocytes than bacillus Calmette-Guerin plus anti-interleukin-10 mAb. Bacillus Calmette-Guerin plus anti-interleukin-10 receptor 1 mAb also induced significantly higher interferon-gamma mRNA and protein in bladder and urine, respectively, in a dose dependent manner. Treatment with phosphate buffered saline, bacillus Calmette-Guerin plus control IgG1 and bacillus Calmette-Guerin plus anti-interleukin-10 receptor 1 mAb showed a 0% tumor-free rate with a 20% death rate, a 20% tumor-free rate with a 20% death rate and a 40% tumor-free rate with a 0% death rate, respectively. Bladder weight also revealed the effect of anti-interleukin-10 receptor 1 mAb on the bacillus Calmette-Guerin induced bladder tumor response.
Conclusions: Anti-interleukin-10 receptor 1 mAb enhanced the bacillus Calmette-Guerin induced T-helper type 1 immune response and anti-bladder cancer immunity. A humanized form of this mAb warrants future investigation for bacillus Calmette-Guerin treatment of bladder cancer.
Details
- Title: Subtitle
- Anti-Interleukin-10R1 Monoclonal Antibody Enhances Bacillus Calmette-Guerin Induced T-Helper Type 1 Immune Responses and Antitumor Immunity in a Mouse Orthotopic Model of Bladder Cancer
- Creators
- Nathan A. Bockholt - University of IowaMatthew J. Knudson - University of IowaJonathan R. Henning - University of IowaJose L. Maymi - University of IowaPeter Weady - University of IowaGeorge J. Smith - University of IowaMichael D. Eisenbraun - University of IowaJames D. Fraser - University of IowaMichael A. O'DonnellYi Luo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.187(6), pp.2228-2235
- Publisher
- Elsevier
- DOI
- 10.1016/j.juro.2012.01.030
- PMID
- 22503050
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Number of pages
- 8
- Grant note
- Pfizer
- Language
- English
- Date published
- 06/01/2012
- Academic Unit
- Urology
- Record Identifier
- 9984319992702771
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