Effectiveness of the combination of vascular targeted photodynamic therapy and anti‐cytotoxic T‐lymphocyte‐associated antigen 4 in a preclinical mouse model of urothelial carcinoma. (18th January 2019) - Corradi, Renato B
Abstract : Objective: To investigate the effectiveness of combination treatment of vascular targeted photodynamic therapy and anti‐cytotoxic T‐lymphocyte‐associated antigen 4 immunotherapy in a mouse model of urothelial carcinoma. Methods: We used C57BL/6 mice injected with murine bladder 49 cell line. Mice were randomly allocated into four treatment groups: vascular targeted photodynamic therapy only, anti‐cytotoxic T‐lymphocyte‐associated antigen 4 only, combination therapy and control. We carried out three separate experiments that used distinct cohorts of mice: tumor growth and development of lung metastases monitored with bioluminescent imaging ( n = 91); survival evaluated with Kaplan–Meier curves ( n = 111); and tumor cell population studied with flow cytometry ( n = 20). In a fourth experiment, we re‐challenged tumors in previously treated mice and compared tumor growth with that of naïve mice. Results: Combination therapy provided significant benefits over the other three treatment groups: prolonged survival ( P < 0.0001), lower tumor signal ( P < 0.0001) and decreased lung signal uptake ( P ≤ 0.002). We also observed that mice previously treated with vascular targeted photodynamic therapy only or combination therapy did not present tumor growth after re‐challenged tumors. Conclusions: Combination of vascular targeted photodynamic therapy with anti‐cytotoxic T‐lymphocyte‐associated antigen 4 is an effective therapy in a urothelial carcinoma syngeneic mouse model. The present results suggest this therapy as a potential treatment option for both bladder and upper tract tumors in future clinical trials.