Combination immunotherapy of murine transitional cell cancer using BCG and an interferon-inducing pyrimidinone.
The immunomodulator ABPP (2-amino-5-iodo-6-phenyl-4(3H) pyrimidinone) is an interferon inducer and has been shown to have in vivo activity against the murine bladder tumor MBT-2. Two experiments were performed to determine if ABPP might enhance the in vivo anti-tumor activity of Bacillus Calmette-Guerin (BCG). First, in vivo stimulation of cell-mediated cytotoxicity by BCG and ABPP was measured in C3H mice using a chromium-release assay. An earlier, greater, and longer-lasting increase in cytotoxicity was caused by ABPP than by BCG. Based on the differing times to peak cytotoxic stimulation, groups of 15 mice each were pretreated intraperitoneally at different times prior to inoculation with MBT-2. Compared to saline, ABPP alone did not increase survival, while BCG alone did increase survival (p less than 0.01), and the combination of BCG and ABPP yielded the highest survival (p less than 0.001). These results indicate that 1) ABPP affects the immune system differently than BCG, and 2) while ABPP may have less single-agent activity against MBT-2 than BCG, ABPP may serve to potentiate the activity of BCG.
Sarosdy
M F
MF
Division of Urology, University of Texas Health Science Center, San Antonio 78284.
Kierum
C A
CA
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007369:Interferon Inducers / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*
D001500:BCG Vaccine; D007369:Interferon Inducers; C033561:2-amino-5-iodo-6-phenyl-4-pyrimidinone; D003596:Cytosine