Antineoplastic effect of immunostimulatory DNA (CpG-ODN) in a murine C57-BL6/MB-49 transitional cell carcinoma model.
BACKGROUND
Intravesical BCG installation is the standard of care in the prophylaxis of recurrent intermediate and high-risk transitional cell carcinoma (TCC), but its mode of action has not yet been elucidated. However, a Th-1 biased immune response is postulated Cell culture and animal models demonstrated the efficacy of synthetic CpG-oligodeoxynucleotides (ODN) as inducer and adjuvant for a strong Th1-response. The purpose of our study was to evaluate the antineoplastic effect of locally administered CpG ODN in a subcutaneous murine bladder cancer model.


METHODS
A subcutaneous murine TCC model was established in female C57/BL6 mice using the corresponding syngeneic MB49 TCC cell line. Three groups of 5 animals received a cell suspension, standardized for 1x10(6) cells/50 microl, injected s.c. into the right and left flank. Group I received 10 nmol of CpG-ODN only into the right cell depot. Group II received 10 nmol of GpC ODN. Group III served as untreated control and received only PBS. The animals were examined at various time points after injection until sacrifice on day 14. Tumor or scar tissue were excised, weighed and examined histopathologically (HE-stain).


RESULTS
Tumor sizes and weights showed no side differences. The average tumor weight on day 14 was 171 mg (SD +/- 8.9), 110 mg (SD +/- 19.2) and 18 mg (SD +/- 6.1), respectively, in groups III, II and I (p<0.05). Histopathology revealed solid vital epithelial tumors in group III and reduced vital tumor mass with central necrosis and moderate mononuclear infiltration in group II. Group I showed almost complete tumor necrosis and a considerable mononuclear inflammatory response.


CONCLUSIONS
Immunostimulatory DNA has promising antineoplastic activity in a murine subcutaneous TCC-model. The histological findings suggest an immunologically-mediated mode of action. Further investigations are necessary to elucidate the immunological response.
Hegele
Axel
A
Department of Urology and Pediatric Urology, Philipps University, Marburg, Germany. hegele@med.uni-marburg.de
Dalpke
Alexander
A
Barth
Peter
P
Varga
Zoltan
Z
Heeg
Klaus
K
Hofmann
Rainer
R
Olbert
Peter
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides