期刊
ONCOIMMUNOLOGY
卷 5, 期 3, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2015.1083670
关键词
Cancer; DNA vaccines; electrogene transfer; electroporation; hTERT; immunotherapy
资金
- Paris Region IDF
- FUI
- ANRT
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.
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