Pharmacological biocompatibility between intravesical preparations of BCG and interferon-alpha 2B.
OBJECTIVE
To determine if BCG and interferon alpha-2B are mutually compatible as mixed intravesical agents for clinical bladder cancer therapy.


METHODS
Mutual compatibility was assessed by measuring IFN-alpha's effect on BCG metabolic activity, growth rate, and clumping tendency and conversely by observing BCG's effect on IFN-alpha's anti-viral activity. Optical density at 600 nm. (OD600) was used to estimate the number of colony forming units of BCG in suspension during 3 hours measurements of clumping and 8 days measurements of BCG proliferation. BCG viability was evaluated using a substrate marker, MTT, which correlates with BCG density and metabolic activity. The anti-viral activity of IFN-alpha was determined in a cytopathic protection bioassay using the encephalomyocarditis virus/FS-4 cell system.


RESULTS
Continuous shaking of reconstituted BCG for 3 hours at 37C resulted in a marginal (11.3%) drop in OD600 which was minimally altered by inclusion of IFN-alpha at 2 million units (MU)/ml. (12.7% drop). Metabolic activity and growth rate of BCG alone or BCG with IFN-alpha were essentially identical. IFN-alpha's antiviral activity was not affected by incubation with BCG.


CONCLUSIONS
The inclusion of IFN-alpha into the usual BCG formulation for intravesical administration has no apparent effect on BCG's viability or tendency to form clumps in suspension. Similarly, the physical mixing of IFN-alpha with BCG does not impair its biological activity. Thus, both agents are pharmacologically compatible for future clinical studies involving combination intravesical therapy.
Downs
T M
TM
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Szilvasi
A
A
O'Donnell
M A
MA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001500:BCG Vaccine / Q000494:pharmacology*; D004347:Drug Interactions; D004686:Encephalomyocarditis virus / Q000187:drug effects* / Q000254:growth & development*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development*; D011994:Recombinant Proteins; D001749:Urinary Bladder Neoplasms / Q000628:therapy
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D001500:BCG Vaccine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins