1. Academic Validation
  2. Photodynamic therapy-improved oncolytic bacterial immunotherapy with FAP-encoding S. typhimurium

Photodynamic therapy-improved oncolytic bacterial immunotherapy with FAP-encoding S. typhimurium

  • J Control Release. 2022 Oct 10;351:860-871. doi: 10.1016/j.jconrel.2022.09.050.
Yanxia Guo 1 Mingxia Song 2 Xiaoqing Liu 1 Yu Chen 1 Zhen Xun 2 Yujie Sun 1 Wenzhi Tan 1 Jianjun He 3 Jin Hai Zheng 4
Affiliations

Affiliations

  • 1 School of Biomedical Sciences, Hunan University, Changsha 410082, China.
  • 2 State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
  • 3 School of Biomedical Sciences, Hunan University, Changsha 410082, China. Electronic address: jianjunh@hnu.edu.cn.
  • 4 School of Biomedical Sciences, Hunan University, Changsha 410082, China. Electronic address: jhzheng@hnu.edu.cn.
Abstract

Genetically engineered Bacterial cancer therapy presents several advantages over conventional therapies. However, the Anticancer effects of bacterium-based therapies remain insufficient, and serious side effects may be incurred with the increase in therapeutic dosages. Photodynamic therapy (PDT) suppresses tumor growth by producing Reactive Oxygen Species (ROS) through specific laser-activated photosensitizers (PSs). Tumor-specific PS delivery and activatable ROS generation are two critical aspects for PDT advancement. Here, we propose PDT-enhanced oncolytic Bacterial immunotherapy (OBI) by using genetically engineered avirulent Salmonella expressing a fluorogen-activating protein (FAP). Upon binding to a fluorogen, FAP could be activated and generate fluorescence and ROS. The instant activation of persistent fluorescence was detected in tumors through bacterium-based imaging. In a colon Cancer model, PDT-OBI showed an enhanced tumor inhibition effect and prolonged animal survival. Mechanically, PDT generated ROS, resulting in the killing of Cancer cells and over-accumulated bacteria. The pathogen-associated molecular patterns and damage-associated molecular patterns released from the destroyed bacteria and Cancer cells recruited and activated immune cells (macrophages, neutrophils, and dendritic cells), which released additional proinflammatory cytokines (TNF-α and IL-1β); reduced anti-inflammatory cytokines (IL-10); and further enhanced immune cell infiltration in a positive-feedback manner, thus reducing bacterium-induced side effects and improving Anticancer activities. This synergistic therapy has promising potential for Cancer Immunotherapy.

Keywords

Cancer immunotherapy; Fluorogen-activating protein (FAP); In vivo imaging; Photodynamic therapy (PDT); Salmonella typhimurium.

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