Pharmacological biocompatibility between intravesical preparations of BCG and interferon-alpha 2B

• Published in: The Journal of urology Vol. 158; no. 6; p. 2311
• Main Authors: Downs, T M, Szilvasi, A, O'Donnell, M A
• Format: Journal Article
• Language: English
• Published: United States 01.12.1997
• Subjects: Adjuvants, Immunologic - pharmacology; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - pharmacology; BCG Vaccine - pharmacology; Drug Interactions; Encephalomyocarditis virus - drug effects; Encephalomyocarditis virus - growth & development; Interferon alpha-2; Interferon-alpha - pharmacology; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - growth & development; Recombinant Proteins; Urinary Bladder Neoplasms - therapy
• ISSN: 0022-5347
• DOI: 10.1016/S0022-5347(01)68241-7

To determine if BCG and interferon alpha-2B are mutually compatible as mixed intravesical agents for clinical bladder cancer therapy. 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. 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. 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.