1. 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
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Corradi RB, LaRosa S, Jebiwott S, Murray KS, Rosenzweig B, Somma AJ, Gomez RS, Scherz A, Kim K, and Coleman JA
- Subjects
- Animals, CTLA-4 Antigen immunology, Carcinoma, Transitional Cell blood supply, Carcinoma, Transitional Cell immunology, Carcinoma, Transitional Cell secondary, Cell Line, Tumor transplantation, Disease Models, Animal, Humans, Luminescent Measurements, Lung blood supply, Lung diagnostic imaging, Lung drug effects, Lung radiation effects, Lung Neoplasms blood supply, Lung Neoplasms immunology, Lung Neoplasms secondary, Male, Mice, Mice, Inbred C57BL, Urinary Bladder blood supply, Urinary Bladder drug effects, Urinary Bladder immunology, Urinary Bladder radiation effects, Urinary Bladder Neoplasms blood supply, Urinary Bladder Neoplasms immunology, Urinary Bladder Neoplasms pathology, CTLA-4 Antigen antagonists & inhibitors, Carcinoma, Transitional Cell therapy, Lung Neoplasms drug therapy, Photochemotherapy methods, Urinary Bladder Neoplasms therapy
- 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., (© 2019 The Japanese Urological Association.)
- Published
- 2019
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