The therapeutic potential of recombinant BCG expressing the antigen S1PT in the intravesical treatment of bladder cancer.

Abstract

PURPOSE:

Bacillus Calmette-Guerin (BCG) continues to be employed as the most effective immunotherapy against superficial bladder cancer. We have developed an rBCG-S1PT strain that induces a stronger cellular immune response than BCG. This preclinical study was designed to test the potential of rBCG-S1PT as an immunotherapeutic agent for intravesical bladder cancer therapy.

MATERIALS AND METHODS:

A tumor was induced in C57BL/6 mice after chemical cauterization of the bladder and inoculation of the tumor cell line MB49. Next, mice were treated by intravesical instillation with BCG, rBCG-S1PT, or PBS once a week for 4 weeks. After 35 days, the bladders were removed and weighed, Th1 (IL-2, IL-12, INOS, INF-gamma, TNF-alpha), and Th2 (IL-5, IL-6, IL-10, TGF-beta) cytokine mRNA responses in individual mice bladders were measured by quantitative real time PCR, and the viability of MB49 cells in 18-hour coculture with splenocytes from treated mice was assessed. In an equivalent experiment, animals were observed for 60 days to quantify their survival.

RESULTS:

Both BCG and rBCG-S1PT immunotherapy resulted in bladder weight reduction, and rBCG-S1PT increased survival time compared with the control group. There were increases in TNF-alpha in the BCG treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. The viability of MB49 cells cocultured with splenocytes from rBCG-S1PT-treated mice was lower than in both the BCG and control groups.

CONCLUSIONS:

rBCG-S1PT therapy improved outcomes and lengthened survival times. These results indicate that rBCG could serve as a useful substitute for wild-type BCG.

• Authors: Priscila M Andrade, Daher C Chade, Ricardo C Borra, Ivan P Nascimento, Fabiola E Villanova, Luciana C C Leite, Enrico Andrade, Miguel Srougi
• Journal: Urologic oncology (Urol Oncol) 2010 Sep-Oct Vol. 28 Issue 5 Pg. 520-5 ISSN: 1873-2496 [Electronic] United States
• PMID: 19272796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• BCG Vaccine
• Cytokines
• Recombinant Proteins
• Pertussis Toxin

Topics

• Administration, Intravesical
• Animals
• BCG Vaccine (administration & dosage)
• Cell Line, Tumor
• Cytokines (genetics)
• Female
• Immunotherapy
• Mice
• Mice, Inbred C57BL
• Pertussis Toxin (genetics, immunology)
• Recombinant Proteins (administration & dosage)
• Urinary Bladder Neoplasms (immunology, therapy)