Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice.
Over expression of telomerase represents a hallmark of cancer cells and the induction of T cell immunity against this universal tumor antigen have gained promising interest for anticancer immunotherapy. In this study we evaluated a recombinant lentiviral vector expressing the human telomerase reverse transcriptase (lv-hTERT) vaccination in the humanized HLA-B*0702 transgenic (HLA-B7 Tg) mice. A single lv-hTERT vector immunization induces potent and broad HLA-B7-restricted CTL responses against hTERT. Unlike conventional hTERT peptide or DNA immunization, the lv-hTERT vector triggers high and sustained IFN-gamma producing CD8(+) T cell responses in HLA-B7 Tg mice. The avidity and in vivo cytotoxicity of CD8(+) T cells were stronger in lv-hTERT vector-immunized mice than in hTERT peptide or DNA vaccinated groups. The study also showed that the use of prime-boost vaccination drastically improved the magnitude and strength of lentivector-primed CD8(+) T cells. Our data indicated that lentiviral delivery of hTERT is suitable for enhancing cellular immunity against hTERT and offers a promising alternative for telomerase-based cancer vaccine.
Rusakiewicz
Sylvie
S
UMRS 970, université Paris Descartes, France.
Dosset
Magalie
M
Mollier
Karine
K
Souque
Philippe
P
Charneau
Pierre
P
Wain-Hobson
Simon
S
Langlade-Demoyen
Pierre
P
Adotévi
Olivier
O
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics; D015793:HLA-B7 Antigen; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D016086:Lentivirus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
D019496:Cancer Vaccines; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D007371:Interferon-gamma; C509186:TERT protein, human; D019098:Telomerase