Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33808256

Citations 8

Authors

Federico Armando

Adnan Fayyad

Stefanie Arms

Yvonne Barthel

Dirk Schaudien

Karl Rohn

Matteo Gambini

Mara Sophie Lombardo

Andreas Beineke

Wolfgang Baumgartner

Christina Puff

Affiliations

Soon will be listed here.

Abstract

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.

Citing Articles

Persistence of Infectious Canine Distemper Virus in Murine Xenotransplants of Canine Histiocytic Sarcoma Cells after Intratumoral Application.

Lombardo M, Armando F, Marek K, Rohn K, Baumgartner W, Puff C Int J Mol Sci. 2024; 25(15).

PMID: 39125874 PMC: 11311720. DOI: 10.3390/ijms25158297.

Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.

Gujar S, Pol J, Kumar V, Lizarralde-Guerrero M, Konda P, Kroemer G Nat Protoc. 2024; 19(9):2540-2570.

PMID: 38769145 DOI: 10.1038/s41596-024-00985-1.

The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors.

Wang G, Cao J, Gui M, Huang P, Zhang L, Qi R J Exp Clin Cancer Res. 2023; 42(1):284.

PMID: 37891570 PMC: 10604416. DOI: 10.1186/s13046-023-02848-1.

Functional Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Delivered by Canine Histiocytic Sarcoma Cells Persistently Infected with Engineered Attenuated Canine Distemper Virus.

Marek K, Armando F, Asawapattanakul T, Nippold V, Plattet P, Gerold G Pathogens. 2023; 12(7).

PMID: 37513724 PMC: 10385001. DOI: 10.3390/pathogens12070877.

Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2.

Heydemann L, Ciurkiewicz M, Beythien G, Becker K, Schughart K, Stanelle-Bertram S Nat Commun. 2023; 14(1):3267.

PMID: 37277327 PMC: 10241385. DOI: 10.1038/s41467-023-39049-5.

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