ABSTRACT
Bladder cancer is a frequent malignancy and has a clinical need for new therapeutic approaches. Antibody and protein technologies came a long way in recent years and new engineering approaches were applied to generate innovative therapeutic entities with novel mechanisms of action. Furthermore, mRNA-based pharmaceuticals recently reached the market and CAR-T cells and viral-based gene therapy remain a major focus of biomedical research. This review focuses on the engineering of biologics, particularly therapeutic antibodies and their application in preclinical development and clinical trials, as well as approved monoclonal antibodies for the treatment of bladder cancer. Besides, newly emerging entities in the realm of bladder cancer like mRNA, gene therapy or cell-based therapeutics are discussed and evaluated. As many discussed molecules exhibit unique mechanisms of action based on innovative protein engineering, they reflect the next generation of cancer drugs. This review will shed light on the engineering strategies applied to develop these next generation treatments and provides deeper insights into their preclinical profiles, clinical stages, and ongoing trials. Furthermore, the distribution and expression of the targeted antigens and the intended mechanisms of action are elucidated.
ABSTRACT
OBJECTIVE: Ureterorenoscopy causes complications that may be related to high intrarenal pressures generated during irrigation. Endoluminal isoproterenol administration has been shown to reduce pelvic pressure in pigs. The objective of this study was to investigate possible systemic side-effects of isoproterenol irrigation during ureterorenoscopy in humans. MATERIAL AND METHODS: Seven patients undergoing ureterorenoscopy due to renal stone disease were included. A 5-Fr catheter was retrogradely placed in the renal pelvis for pressure measurements. Prior to irrigation with isoproterenol (0.1 microg/ml), ureterorenoscopy was performed with saline irrigation. Renal pelvic pressure, blood pressure and heart rate were measured before and after isoproterenol irrigation. Venous blood was drawn for isoproterenol measurements. RESULTS: Endoluminal isoproterenol irrigation produced no changes in mean heart rate (HR) or mean arterial pressure (MAP). MAP (+/- SEM) was 56 (2.7) mmHg during saline irrigation and 58 (+/- 2.4) mmHg during isoproterenol irrigation. HR was 60 (+/- 4) beats/min before and 61 (+/- 4) beats/min during isoproterenol irrigation. Neither the difference in MAP = 0.10) nor the difference in HR (p = 0.23) were significant. Pelvic pressure was significantly lower during isoproterenol irrigation [19 (+/- 3) mmHg] compared to saline irrigation [35 (+/- 2.6) mmHg] (p = 0.0006). Pelvic pressure reached very high levels (> 300 mmHg), especially during injection of contrast medium. CONCLUSION: Endoluminal isoproterenol irrigation during ureterorenoscopy causes no cardiovascular side-effects and the drug may reduce renal pelvic pressure.