Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response. (3rd March 2016)

• Record Type: Journal Article
• Authors: Thalmensi, Jessie; Pliquet, Elodie; Liard, Christelle; Escande, Marie; Bestetti, Thomas; Julithe, Marion; Kostrzak, Anna; Pailhes-Jimenez, Anne-Sophie; Bourges, Emanuèle; Loustau, Maria; Caumartin, Julien; Lachgar, Abderrahim; Huet, Thierry; Wain-Hobson, Simon; Langlade-Demoyen, Pierre
• Is Part Of: Oncoimmunology. Volume 5:Number 3(2016)
• Publication Date: 2016-03-03
• Subjects: Cancer -- DNA vaccines -- electrogene transfer -- electroporation -- hTERT -- immunotherapy; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2015.1083670
• Languages: English
• ISSNs: 2162-402X

Abstract

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.