Oncolytic bacteria VNP20009 expressing IFNβ inhibits melanoma progression by remodeling the tumor microenvironment
Lina Liu,
Qiang Li,
Chen Chen,
Wenjie Xin,
Chao Han,
Zichun Hua
Affiliations
Lina Liu
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China
Qiang Li
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China
Chen Chen
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China
Wenjie Xin
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China
Chao Han
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China
Zichun Hua
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences; Nanjing University, Nanjing 210023, Jiangsu, China; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu, Changzhou, Jiangsu 213164, China; TargetPharma Laboratories Inc, Changzhou 213164, Jiangsu, China; Corresponding author
Summary: In the tumor microenvironment (TME), tumor-associated NEs (TANs) have the potential to be protumorigenic or antitumorigenic within the TME in response to environmental cues. The diversity and plasticity of NEs (NEs) underlie the dual potential of TANs in the TME. Here, we utilized the tumor-targeting bacterium VNP20009 (VNP) to carry a plasmid expressed IFNβ (VNP-IFNβ), which can deliver IFNβ and remodel TANs to an antitumorigenic phenotype, and performed preclinical evaluations in the B16F10 lung metastasis model and the B16F10 subcutaneous xenograft model. Compared with VNP, VNP-IFNβ recruited more NEs and macrophages (Mφs) with antitumor phenotypes in lung metastases and activated dendritic cells (DCs) differentiation, which activated antitumor immune responses of CD4+ T cells, and ultimately inhibited melanoma progression. This study enriches the bacterial-mediated tumor therapy by using tumor-targeting bacteria to deliver IFNβ to the tumor site and inhibit melanoma growth and metastasis by remodeling the tumor immune microenvironment.
