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Macrophage-mediated tumor-targeted delivery of engineered Salmonella typhi murium VNP20009 in anti-PD1 therapy against melanoma.

Macrophage-mediated tumor-targeted delivery of engineered Salmonella typhi murium VNP20009 in anti-PD1 therapy against melanoma.

Authors :
Wu L
Li L
Li S
Liu L
Xin W
Li C
Yin X
Xu X
Bao F
Hua Z
Source :
Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2022 Oct; Vol. 12 (10), pp. 3952-3971. Date of Electronic Publication: 2022 May 14.
Publication Year :
2022

Abstract

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8 <superscript>+</superscript> T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8 <superscript>+</superscript> T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.<br /> (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Details

Language :
English
ISSN :
2211-3835
Volume :
12
Issue :
10
Database :
MEDLINE
Journal :
Acta pharmaceutica Sinica. B
Publication Type :
Academic Journal
Accession number :
36213533
Full Text :
https://doi.org/10.1016/j.apsb.2022.05.006