Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model.
BACKGROUND
Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-alpha and IL-10 expression and to evaluate antitumour activity.


METHODS
For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF- and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells.


RESULTS
rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and 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.


CONCLUSIONS
These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-alpha and IL-10 cytokine productions may have therapeutic value.
Chade
Daher C
DC
Division of Urology, Laboratory of Medical Investigation University of São Paulo, São Paulo, Brazil. pmborra@gmail.com
Borra
Ricardo C
RC
Nascimento
Ivan P
IP
Villanova
Fabiola E
FE
Leite
Luciana C C
LC
Andrade
Enrico
E
Srougi
Miguel
M
Ramos
Kátia L
KL
Andrade
Priscila M
PM
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D037342:Pertussis Toxin / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
D001500:BCG Vaccine; D019496:Cancer Vaccines; D007155:Immunologic Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D037342:Pertussis Toxin