A DNA telomerase vaccine for canine cancer immunotherapy
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Jessie Thalmensi1, Elodie Pliquet1, Christelle Liard1, Gabriel Chamel1, Christine Kreuz2, Thomas Bestetti1, Marie Escande1, Anna Kostrzak1, Anne-Sophie Pailhes-Jimenez1, Emmanuèle Bourges1, Marion Julithe1, Ludovic Bourre1, Olivier Keravel3, Pascal Clayette2, Thierry Huet1, Simon Wain-Hobson1,4 and Pierre Langlade-Demoyen1,4
1 Invectys, Paris BioPark, Paris 75013, France
2 ImmunoPharmacology and Biosafety Lab, Bertin Pharma/CEA, Fontenay-aux-Roses 92265, France
3 Eiffelvet, Paris 75015, France
4 Molecular Retrovirology Unit, Institut Pasteur, CNRS-URA 3015, Paris 75015, France
Keywords: DNA vaccine; canine TERT; cancer; immunotherapy; Electro-Gene-Transfer
Received: May 20, 2016 Accepted: April 29, 2019 Published: May 21, 2019
Telomerase reverse transcriptase (TERT) is highly expressed in more than 90% of canine cancer cells and low to absent in normal cells. Given that immune tolerance to telomerase is easily broken both naturally and experimentally, telomerase is an attractive tumor associated antigen for cancer immunotherapy. Indeed, therapeutic trials using human telomerase peptides have been performed. We have developed an immunogenic yet catalytically inactive human telomerase DNA construct that is in clinical trials with patients presenting solid tumors. Paralleling this human construct, we have developed a canine telomerase DNA vaccine, called pDUV5. When administered intradermally to mice combined with electrogene transfer, pDUV5 induced canine TERT specific cytotoxic T-cells as measured by IFN-γ ELISpot assay. Intradermal vaccination of healthy dogs with 400 μg of pDUV5 generated strong, broad and long lasting TERT specific cellular immune responses. In vitro immunization with cTERT peptides revealed the maintenance of cTERT specific T-cells in PBMCs from tumor bearing dogs showing that this repertoire was not depleted. This study highlights the potential of pDUV5 as a cancer vaccine and supports its evaluation for the treatment of spontaneous canine tumors.
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