小鼠原位膀胱癌模型血管靶向光动力疗法的选择性及抗肿瘤免疫增强作用

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.