Downs T M, Szilvasi A, O'Donnell M A
Department of Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
J Urol. 1997 Dec;158(6):2311-5. 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.
确定卡介苗（BCG）和干扰素α-2B作为混合膀胱内用药用于临床膀胱癌治疗时是否相互兼容。
通过测量干扰素α对卡介苗代谢活性、生长速率和聚集倾向的影响来评估相互兼容性，反之，通过观察卡介苗对干扰素α抗病毒活性的影响来评估。使用600nm处的光密度（OD600）来估计悬浮液中卡介苗集落形成单位的数量，在3小时的聚集测量和8天的卡介苗增殖测量期间进行。使用与卡介苗密度和代谢活性相关的底物标记物MTT评估卡介苗的活力。在使用脑心肌炎病毒/FS-4细胞系统的细胞病变保护生物测定中确定干扰素α的抗病毒活性。
重组卡介苗在37℃连续振荡3小时导致OD600略有下降（11.3%），加入200万单位（MU）/ml的干扰素α后变化最小（下降12.7%）。单独的卡介苗或卡介苗与干扰素α一起的代谢活性和生长速率基本相同。干扰素α的抗病毒活性不受与卡介苗孵育的影响。
在用于膀胱内给药的常规卡介苗制剂中加入干扰素α对卡介苗的活力或在悬浮液中形成团块的倾向没有明显影响。同样，干扰素α与卡介苗的物理混合不会损害其生物活性。因此，这两种药物在未来涉及联合膀胱内治疗的临床研究中在药理学上是兼容的。
