Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response.

Autor:	Thalmensi J; Invectys, Pasteur BioTop , Paris, France., Pliquet E; Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France., Liard C; Invectys, Pasteur BioTop , Paris, France., Escande M; Invectys, Pasteur BioTop , Paris, France., Bestetti T; Invectys, Pasteur BioTop , Paris, France., Julithe M; Invectys, Pasteur BioTop , Paris, France., Kostrzak A; Invectys, Pasteur BioTop , Paris, France., Pailhes-Jimenez AS; Invectys, Pasteur BioTop , Paris, France., Bourges E; Invectys, Pasteur BioTop , Paris, France., Loustau M; Invectys, Pasteur BioTop , Paris, France., Caumartin J; Invectys, Pasteur BioTop , Paris, France., Lachgar A; Invectys, Pasteur BioTop , Paris, France., Huet T; Invectys, Pasteur BioTop , Paris, France., Wain-Hobson S; Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France., Langlade-Demoyen P; Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2015 Nov 05; Vol. 5 (3), pp. e1083670. Date of Electronic Publication: 2015 Nov 05 (Print Publication: 2016).
DOI:	10.1080/2162402X.2015.1083670
Abstrakt:	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.
Databáze:	MEDLINE
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