Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors
TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tum...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770523000529 |
| _version_ | 1827866242089746432 |
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| author | Jérémy Béguin Eve Laloy Sandrine Cochin Murielle Gantzer Isabelle Farine Christelle Pichon Baptiste Moreau Johann Foloppe Jean-Marc Balloul Christelle Machon Jérôme Guitton Dominique Tierny Bernard Klonjkowski Eric Quéméneur Christelle Maurey Philippe Erbs |
| author_facet | Jérémy Béguin Eve Laloy Sandrine Cochin Murielle Gantzer Isabelle Farine Christelle Pichon Baptiste Moreau Johann Foloppe Jean-Marc Balloul Christelle Machon Jérôme Guitton Dominique Tierny Bernard Klonjkowski Eric Quéméneur Christelle Maurey Philippe Erbs |
| author_sort | Jérémy Béguin |
| collection | DOAJ |
| description | TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine. The viral genome was assessed in blood and tumor biopsies by qPCR. 5-Fluorouracil concentrations were measured in serum and tumor biopsies by liquid chromatography or high-resolution mass spectrometry. Histological and immunohistochemical analyses were performed. The viral genome was detected in blood (7/13) and tumor biopsies (4/11). Viral replication was suspected in 6/13 dogs. The median intratumoral concentration of 5-fluorouracil was 314 pg/mg. 5-Fluorouracil was not detected in the blood. An increase in necrosis (6/9) and a downregulation of intratumoral regulatory T lymphocytes (6/6) were observed. Viral replication, 5-fluorouracil synthesis, and tumor microenvironment changes were more frequently observed with higher TG6002 doses. This study confirmed the replicative properties, targeted chemotherapy synthesis, and reversion of the immunosuppressive tumor microenvironment in dogs with spontaneous malignant tumors treated with TG6002 and 5-fluorocytosine. |
| first_indexed | 2024-03-12T15:01:08Z |
| format | Article |
| id | doaj.art-158089590f2b4c318c0aec5c6f69e200 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-03-12T15:01:08Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-158089590f2b4c318c0aec5c6f69e2002023-08-14T04:07:45ZengElsevierMolecular Therapy: Oncolytics2372-77052023-09-0130103116Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumorsJérémy Béguin0Eve Laloy1Sandrine Cochin2Murielle Gantzer3Isabelle Farine4Christelle Pichon5Baptiste Moreau6Johann Foloppe7Jean-Marc Balloul8Christelle Machon9Jérôme Guitton10Dominique Tierny11Bernard Klonjkowski12Eric Quéméneur13Christelle Maurey14Philippe Erbs15Transgene, 67405 Illkirch-Graffenstaden, France; UMR Virologie, INRAE, École Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France; Department of Internal Medicine, École Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceUMR Virologie, INRAE, École Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, France; Anatomical Pathology Unit, Biopôle, École Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceService de Biochimie et pharmacotoxicologie, Hôpital Lyon-Sud, Hospices Civils de Lyon, 69310, FranceService de Biochimie et pharmacotoxicologie, Hôpital Lyon-Sud, Hospices Civils de Lyon, 69310, FranceOncovet Clinical Research, 59120 Loos, FranceUMR Virologie, INRAE, École Nationale Vétérinaire d’Alfort, ANSES, Université Paris-Est, 94700 Maisons-Alfort, FranceTransgene, 67405 Illkirch-Graffenstaden, FranceDepartment of Internal Medicine, École Nationale Vétérinaire d’Alfort, Université Paris-Est, 94700 Maisons-Alfort, FranceTransgene, 67405 Illkirch-Graffenstaden, France; Corresponding author: Philippe Erbs, 400 Boulevard Gonthier d’Andernach – Parc d'Innovation, Illkirch Graffenstaden, Cedex 67405, France.TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine. The viral genome was assessed in blood and tumor biopsies by qPCR. 5-Fluorouracil concentrations were measured in serum and tumor biopsies by liquid chromatography or high-resolution mass spectrometry. Histological and immunohistochemical analyses were performed. The viral genome was detected in blood (7/13) and tumor biopsies (4/11). Viral replication was suspected in 6/13 dogs. The median intratumoral concentration of 5-fluorouracil was 314 pg/mg. 5-Fluorouracil was not detected in the blood. An increase in necrosis (6/9) and a downregulation of intratumoral regulatory T lymphocytes (6/6) were observed. Viral replication, 5-fluorouracil synthesis, and tumor microenvironment changes were more frequently observed with higher TG6002 doses. This study confirmed the replicative properties, targeted chemotherapy synthesis, and reversion of the immunosuppressive tumor microenvironment in dogs with spontaneous malignant tumors treated with TG6002 and 5-fluorocytosine.http://www.sciencedirect.com/science/article/pii/S2372770523000529oncolytic virotherapyoncolytic virusesimmunomodulationantineoplastic protocolstranslational medical research |
| spellingShingle | Jérémy Béguin Eve Laloy Sandrine Cochin Murielle Gantzer Isabelle Farine Christelle Pichon Baptiste Moreau Johann Foloppe Jean-Marc Balloul Christelle Machon Jérôme Guitton Dominique Tierny Bernard Klonjkowski Eric Quéméneur Christelle Maurey Philippe Erbs Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors Molecular Therapy: Oncolytics oncolytic virotherapy oncolytic viruses immunomodulation antineoplastic protocols translational medical research |
| title | Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors |
| title_full | Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors |
| title_fullStr | Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors |
| title_full_unstemmed | Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors |
| title_short | Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors |
| title_sort | oncolytic virotherapy with intratumoral injection of vaccinia virus tg6002 and 5 fluorocytosine administration in dogs with malignant tumors |
| topic | oncolytic virotherapy oncolytic viruses immunomodulation antineoplastic protocols translational medical research |
| url | http://www.sciencedirect.com/science/article/pii/S2372770523000529 |
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