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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
Author(s) -
Corradi Renato B,
LaRosa Stephen,
Jebiwott Sylvia,
Murray Katie S,
Rosenzweig Barak,
Somma Alexander J,
Gomez Renato S,
Scherz Avigdor,
Kim Kwanghee,
Coleman Jonathan A
Publication year - 2019
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13878
Subject(s) - medicine , photodynamic therapy , cytotoxic t cell , targeted therapy , combination therapy , immunotherapy , antigen , cancer research , lymphocyte , population , immunology , oncology , cancer , immune system , in vitro , biology , biochemistry , chemistry , environmental health , organic chemistry
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.