1. Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response
- Author
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Thierry Huet, Elodie Pliquet, Pierre Langlade-Demoyen, Emanuèle Bourges, Simon Wain-Hobson, Marion Julithe, Anna Kostrzak, Thomas Bestetti, Abderrahim Lachgar, Jessie Thalmensi, Christelle Liard, Marie Escande, Julien Caumartin, Anne-Sophie Pailhes-Jimenez, and Maria Loustau
- Subjects
Cellular immunity ,medicine.medical_treatment ,Immunology ,Immunotherapy ,Biology ,DNA vaccination ,03 medical and health sciences ,CTL ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Telomerase reverse transcriptase ,Cancer vaccine ,Original Research ,030215 immunology - 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.
- Published
- 2015