title: Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response.
abstract: Human telomerase reverse transcriptase (hTERT) is overexpressed in more than 85% of human cancers regardless of their cellular origin. As immunological tolerance to hTERT can be overcome not only spontaneously but also by vaccination, it represents a relevant universal tumor associated antigen (TAA). Indeed, hTERT specific cytotoxic T lymphocyte (CTL) precursors are present within the peripheral T-cell repertoire. Consequently, hTERT vaccine represents an attractive candidate for antitumor immunotherapy. Here, an optimized DNA plasmid encoding an inactivated form of hTERT, named INVAC-1, was designed in order to trigger cellular immunity against tumors. Intradermal injection of INVAC-1 followed by electrogene transfer (EGT) in a variety of mouse models elicited broad hTERT specific cellular immune responses including high CD4+Th1 effector and memory CD8+T‑cells. Furthermore, therapeutic INVAC‑1 immunization in a HLA-A2 spontaneous and aggressive mouse sarcoma model slows tumor growth and increases survival rate of 50% of tumor-bearing mice. These results emphasize that INVAC-1 based immunotherapy represents a relevant cancer vaccine candidate.
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Jessie
authors.initials: J
authors.lastname: Thalmensi
authors.affiliation: Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Pliquet
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Liard
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Escande
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bestetti
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Julithe
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kostrzak
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Pailhes-Jimenez
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Emanuèle
authors.initials: E
authors.lastname: Bourges
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Loustau
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Caumartin
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Lachgar
authors.affiliation: Invectys, Pasteur BioTop , Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Huet
authors.affiliation: Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
authors.affiliation: Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Langlade-Demoyen
keywords: Cancer; DNA vaccines; electrogene transfer; electroporation; hTERT; immunotherapy 