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Oncoimmunology. 2015 Nov 5;5(3):e1083670. eCollection 2016 Mar.

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

Author information

1
Invectys, Pasteur BioTop , Paris, France.
2
Invectys, Pasteur BioTop, Paris, France; Molecular Retrovirology Unit, CNRS-URA 3015, Institut Pasteur, Paris, France.

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.

KEYWORDS:

Cancer; DNA vaccines; electrogene transfer; electroporation; hTERT; immunotherapy

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