Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors

Béguin, Jérémy; Laloy, Eve; Cochin, Sandrine; Gantzer, Murielle; Farine, Isabelle; Pichon, Christelle; Moreau, Baptiste; Foloppe, Johann; Balloul, Jean‐Marc; Machon, Christelle; Guitton, Jérôme; Tierny, Dominique; Klonjkowski, Bernard; Quéméneur, Éric; Maurey, Christelle; Erbs, Philippe

doi:10.1016/j.omto.2023.07.005

Cited by 6 publications

(2 citation statements)

References 48 publications

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“…TG6002 is armed with the suicide gene FCU1, encoding a bifunctional chimeric protein that catalyzes the conversion of nontoxic 5-fluorocetosine (5-FC) and 5-fluorouridine monophosphate. The expression of the FCU1 gene by the virus makes it a possible candidate for targeted chemotherapy within the tumor [65]. In preclinical trials, TG6002 showed a convincing antitumor effect in multiple human xenografts, including glioblastoma [31].…”

Section: Other Oncolytic Virusesmentioning

confidence: 99%

Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma

Ageenko,

Vasileva,

Richter

et al. 2024

IJMS

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Glioblastoma is one of the most malignant and aggressive tumors of the central nervous system. Despite the standard therapy consisting of maximal surgical resection and chemo- and radiotherapy, the median survival of patients with this diagnosis is about 15 months. Oncolytic virus therapy is one of the promising areas for the treatment of malignant neoplasms. In this review, we have focused on emphasizing recent achievements in virotherapy, both as a monotherapy and in combination with other therapeutic schemes to improve survival rate and quality of life among patients with glioblastoma.

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Section: Other Oncolytic Virusesmentioning

confidence: 99%

Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma

Ageenko,

Vasileva,

Richter

et al. 2024

IJMS

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“…5-FU concentrations in serum and tumour tissue: Quantification of 5-FC, 5-FU and 5-fluoroβ-alanine (F-BAL) levels was performed using liquid chromatography coupled with highresolution mass spectrometry (Hospices Civils de Lyon, France) as described previously [19].…”

Section: Detection Of Virus In Tumour Biopsies and Plasmamentioning

confidence: 99%

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer

West,

Sadoun,

Bendjama

et al. 2024

Preprint

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Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous (i.v.) or intratumoural (i.t.) administration routes. Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine (5-FC) to fifteen mCRC patients. Results: Successful IHA delivery of replication-competent TG6002 was achieved, as demonstrated by virus within tumour biopsies. Functional transcription of the FCU1 transgene indicates viral replication within the tumour, with higher plasma concentrations of 5-fluorouracil (5-FU) associated with patients receiving the highest dose of TG6002. IHA delivery of TG6002 correlated with a robust systemic peripheral immune response to virus with activation of peripheral blood mononuclear cells, associated with a proinflammatory cytokine response and release of calreticulin, potentially indicating immunogenic cell death. Gene Ontology analyses of differentially-expressed genes reveal a significant immune response at the transcriptional level in response to treatment. Moreover, an increase in the number and frequency of T cell receptor clones against both cancer- and neo-antigens, with elevated functional activity, may be associated with improved anti-cancer activity. Despite these findings, no clinical efficacy was observed. Conclusions: In summary, these data demonstrate delivery of OV to tumour via IHA administration, associated with viral replication and significant peripheral immune activation. Collectively, the data supports the need for future studies using IHA administration of OVs.

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From oncolytic virotherapy to individualized multimodal immunotherapy with focus on glioblastoma

Kampers,

Van de Vliet,

Schirrmacher

et al. 2024

Reference Module in Biomedical Sciences

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Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors

Cited by 6 publications

References 48 publications

Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma

Combination of Oncolytic Virotherapy with Different Antitumor Approaches against Glioblastoma

A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer

From oncolytic virotherapy to individualized multimodal immunotherapy with focus on glioblastoma

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