Selectivity and anti-tumor immune elevation by vascular-targeted photodynamic therapy of mouse orthotopic bladder cancer model.

Abstract

Vascular-targeted photodynamic therapy (VTP) with WST11 is a non-surgical tumor ablation approach that is currently being tested in a phase 3 clinical trial for the treatment of upper tract urothelial cancer. WST11-VTP utilizes illumination, leading to hypoxia, and production of free radicals followed by coagulative necrosis. Here, we tested the hypothesis that WST11-VTP can safely ablate muscle-invasive MB-49- luc bladder tumors in an orthotopic mouse model while sparing the surrounding normal tissue. For the safety study, normal mouse bladders were WST11-VTP treated. Fourteen days post-VTP granulomas in local areas around the ablation zone were noticed, which recovered after 44 days. MB49-luc orthotopic tumors at the muscle-invasive stage appeared to be effectively ablated by VTP 4-10 days post-treatment. The anti-tumor response was reflected in the increased invasion of CD4⁺, CD8⁺ T cells, myeloid CD11b⁺ cells, and NK cells in tumor tissue at 7 days post-therapy. Moreover, VTP therapy prolonged the survival of mice bearing orthotopic tumors compared with the untreated control. These results suggest that VTP can selectively ablate malignant tumors in the bladder and promote a robust anti-tumor response in a mouse model that can further augment the therapeutic outcome.