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

Author:

Marek Katarzyna12,Armando Federico1ORCID,Asawapattanakul Thanaporn12ORCID,Nippold Vanessa Maria1,Plattet Philippe3,Gerold Gisa4567ORCID,Baumgärtner Wolfgang12ORCID,Puff Christina1ORCID

Affiliation:

1. Department of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany

2. Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany

3. Division of Experimental Clinical Research, Vetsuisse University Bern, 3012 Bern, Switzerland

4. Department of Biochemistry, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany

5. Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Germany

6. Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 901 87 Umeå, Sweden

7. Department of Clinical Microbiology, Virology, Umeå University, 901 87 Umeå, Sweden

Abstract

The immune response plays a key role in the treatment of malignant tumors. One important molecule promoting humoral and cellular immunity is granulocyte–macrophage colony-stimulating factor (GM-CSF). Numerous successful trials have led to the approval of this immune-stimulating molecule for cancer therapy. However, besides immune stimulation, GM-CSF may also accelerate tumor cell proliferation, rendering this molecule a double-edged sword in cancer treatment. Therefore, detailed knowledge about the in vitro function of GM-CSF produced by infected tumor cells is urgently needed prior to investigations in an in vivo model. The aim of the present study was to functionally characterize a persistent infection of canine histiocytic sarcoma cells (DH82 cells) with the canine distemper virus strain Onderstepoort genetically engineered to express canine GM-CSF (CDV-Ondneon-GM-CSF). The investigations aimed (1) to prove the overall functionality of the virally induced production of GM-CSF and (2) to determine the effect of GM-CSF on the proliferation and motility of canine HS cells. Infected cells consistently produced high amounts of active, pH-stable GM-CSF, as demonstrated by increased proliferation of HeLa cells. By contrast, DH82 cells lacked increased proliferation and motility. The significantly increased secretion of GM-CSF by persistently CDV-Ondneon-GM-CSF-infected DH82 cells, the pH stability of this protein, and the lack of detrimental effects on DH82 cells renders this virus strain an interesting candidate for future studies aiming to enhance the oncolytic properties of CDV for the treatment of canine histiocytic sarcomas.

Publisher

MDPI AG

Subject

Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,Molecular Biology,Immunology and Allergy

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