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

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)...

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Bibliographic Details
Published in:Oncoimmunology 2016-03, Vol.5 (3), p.e1083670-e1083670
Main 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
Format: Article
Language:English
Subjects:
Cancer
DNA vaccines
electrogene transfer
electroporation
hTERT
immunotherapy
Original Research
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Summary: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.
ISSN:2162-4011
2162-402X
2162-402X
DOI:10.1080/2162402X.2015.1083670