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

被引：16

作者：

Bockholt, Nathan A.

Knudson, Matthew J.

Henning, Jonathan R.

Maymi, Jose L.

Weady, Peter ^{[2
]}

Smith, George J., III ^{[2
]}

Eisenbraun, Michael D. ^{[2
]}

Fraser, James D. ^{[2
]}

O'Donnell, Michael A.

Luo, Yi ^{[1
]}

机构：

[1] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA

[2] Pfizer Inc, San Diego, CA USA

来源：

JOURNAL OF UROLOGY | 2012年 / 187卷 / 06期

关键词：

urinary bladder; urinary bladder neoplasms; interleukin-10 receptor alpha subunit; BCG vaccine; mice; PROGNOSTIC VALUE; TUMOR-GROWTH; IFN-GAMMA; INTERLEUKIN-10; BCG; IL-10; IMMUNOTHERAPY; EXPRESSION; THERAPY; ANTIGEN;

D O I：

10.1016/j.juro.2012.01.030

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

100201 [内科学]; 100221 [泌尿外科学];

摘要：

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.

引用

页码：2228 / 2235

页数：8

共 25 条

[1]

MACROPHAGE DEACTIVATION BY INTERLEUKIN-10 [J].