Abstract
Previous studies have found that use of hexaminolevulinate (HAL) and blue light cystoscopy (BLC) during treatment of bladder cancer had a positive impact on overall survival after later cystectomy, indicating a potential treatment effect beyond improved diagnostic accuracy. The aim of our study was to determine whether HAL and BL mimicking clinically relevant doses in an orthotopic rat model could have therapeutic effect by inducing modulation of a tumor-specific immune response. We also assessed whether administration with a checkpoint inhibitor could potentiate any effects observed. Rats were subjected to HAL BL alone and in combination with anti-PD-L1 and assessed for anti-tumor effects and effects on immune markers. Positive anti-tumor effect was observed in 63% and 31% of rats after, respectively, 12 and 30 days after the procedure, together with a localization effect of CD3+ and CD8+ cells after 30 days. Anti-tumor effect at 30 days increases from 31% up to 38% when combined with intravesical anti-PD-L1. In conclusion, our study demonstrated treatment effects with indications of systemic immune activation at diagnostic doses of HAL and blue light. The observed treatment effect seemed to be enhanced when used in combination with intravesically administrated immune checkpoint inhibitor.
Highlights
IntroductionUrothelial carcinoma is the fifth most prevalent cancer worldwide, where non-muscleinvasive bladder cancer (NMIBC) constitutes 75% of primary diagnosis [1]
We studied the therapeutic effect of HAL and blue light (BL) illumination at different time points after tumor cell inoculation
We have demonstrated an anti-tumor effect of HAL and blue light when trying to mimic the dosing regimen of a photodynamic diagnostic procedure in an orthotropic bladder cancer model in rats
Summary
Urothelial carcinoma is the fifth most prevalent cancer worldwide, where non-muscleinvasive bladder cancer (NMIBC) constitutes 75% of primary diagnosis [1]. NMIBC is characterized by frequent recurrences and progression to muscle-invasive bladder cancer within 24 months after treatment with transurethral resection of bladder tumor (TURBT). Followed by intravesical bacillus Calmette–Guérin (BCG) instillation [2]. Use of the photosensitizer hexaminolevulinate (HAL, Hexvix® ) and blue light cystoscopy (BLC® ) has been introduced to increase detection of tumors during diagnosis and surgical treatment of bladder cancer [3]. HAL induces preferential accumulation of Biomedicines 2022, 10, 548.
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