Neoadjuvant vascular-targeted photodynamic therapy improves survival and reduces recurrence and progression in a mouse model of urothelial cancer. Academic Article uri icon

Overview

abstract

  • Locally advanced urothelial cancer has high recurrence and progression rates following surgical treatment. This highlights the need to develop neoadjuvant strategies that are both effective and well-tolerated. We hypothesized that neoadjuvant sub-ablative vascular-targeted photodynamic therapy (sbVTP), through its immunotherapeutic mechanism, would improve survival and reduce recurrence and progression in a murine model of urothelial cancer. After urothelial tumor implantation and 17 days before surgical resection, mice received neoadjuvant sbVTP (WST11; Tookad Soluble, Steba Biotech, France). Local and systemic response and survival served as measures of therapeutic efficacy, while immunohistochemistry and flow cytometry elucidated the immunotherapeutic mechanism. Data analysis included two-sided Kaplan-Meier, Mann-Whitney, and Fischer exact tests. Tumor volume was significantly smaller in sbVTP-treated animals than in controls (135 mm3 vs. 1222 mm3, P < 0.0001) on the day of surgery. Systemic progression was significantly lower in sbVTP-treated animals (l7% vs. 30%, P < 0.01). Both median progression-free survival and overall survival were significantly greater among animals that received sbVTP and surgery than among animals that received surgery alone (P < 0.05). Neoadjuvant-treated animals also demonstrated significantly lower local recurrence. Neoadjuvant sbVTP was associated with increased early antigen-presenting cells, and subsequent improvements in long-term memory and increases in effector and active T-cells in the spleen, lungs, and blood. In summary, neoadjuvant sbVTP delayed local and systemic progression, prolonged progression-free and overall survival, and reduced local recurrence, thereby demonstrating therapeutic efficacy through an immune-mediated response. These findings strongly support its evaluation in clinical trials.

publication date

  • March 1, 2021

Research

keywords

  • Neoadjuvant Therapy
  • Neoplasms, Experimental
  • Photochemotherapy
  • Urinary Bladder Neoplasms

Identity

PubMed Central ID

  • PMC7921650

Scopus Document Identifier

  • 85102225000

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.166.2.900

PubMed ID

  • 33649388

Additional Document Info

volume

  • 11

issue

  • 1