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


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.
Andrade
Priscila M
PM
Laboratory of Medical Investigation, Division of Urology, University of Sao Paulo, Sao Paulo, Brazil. pmborra@gmail.com
Chade
Daher C
DC
Borra
Ricardo C
RC
Nascimento
Ivan P
IP
Villanova
Fabiola E
FE
Leite
Luciana C C
LC
Andrade
Enrico
E
Srougi
Miguel
M
D000283:Administration, Intravesical; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics; D005260:Female; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
D001500:BCG Vaccine; D016207:Cytokines; D011994:Recombinant Proteins; D037342:Pertussis Toxin