Complementary dual-virus strategy drives synthetic target and cognate T-cell engager expression for endogenous-antigen agnostic immunotherapy.

Autor:	Taha Z; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. ztaha053@uottawa.ca.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. ztaha053@uottawa.ca., Crupi MJF; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. mcrupi@ohri.ca.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. mcrupi@ohri.ca., Alluqmani N; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., MacKenzie D; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Vallati S; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Whelan JT; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Fareez F; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada., Alwithenani A; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Petryk J; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Chen A; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Spinelli MM; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Ng K; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Sobh J; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., de Souza CT; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Bharadwa PR; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Lee TKH; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Thomas DA; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Huang BZ; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Kassas O; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Poutou J; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Gilchrist VH; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Boulton S; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Thomson M; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Marius R; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Hooshyar M; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., McComb S; Cancer Immunology Team, National Research Council of Canada, Human Health Therapeutics, Ottawa, ON, K1A 0R6, Canada., Arulanandam R; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada., Ilkow CS; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada., Bell JC; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. jbell@ohri.ca.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. jbell@ohri.ca., Diallo JS; Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. jsdiallo@ohri.ca.; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada. jsdiallo@ohri.ca.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Aug 23; Vol. 15 (1), pp. 7267. Date of Electronic Publication: 2024 Aug 23.
DOI:	10.1038/s41467-024-51498-0
Abstrakt:	Targeted antineoplastic immunotherapies have achieved remarkable clinical outcomes. However, resistance to these therapies due to target absence or antigen shedding limits their efficacy and excludes tumours from candidacy. To address this limitation, here we engineer an oncolytic rhabdovirus, vesicular stomatitis virus (VSVΔ51), to express a truncated targeted antigen, which allows for HER2-targeting with trastuzumab. The truncated HER2 (HER2T) lacks signaling capabilities and is efficiently expressed on infected cell surfaces. VSVΔ51-mediated HER2T expression simulates HER2-positive status in tumours, enabling effective treatment with the antibody-drug conjugate trastuzumab emtansine in vitro, ex vivo, and in vivo. Additionally, we combine VSVΔ51-HER2T with an oncolytic vaccinia virus expressing a HER2-targeted T-cell engager. This dual-virus therapeutic strategy demonstrates potent curative efficacy in vivo in female mice using CD3+ infiltrate for anti-tumour immunity. Our findings showcase the ability to tailor the tumour microenvironment using oncolytic viruses, thereby enhancing compatibility with "off-the-shelf" targeted therapies. (© 2024. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink