Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice
Authors: Sylvie Rusakiewicz, Magalie Dossetcd, Karine Mollier, Philippe Souque, Pierre Charneau,
Simon Wain-Hobson, Pierre Langlade-Demoyen, Olivier Adotévi
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-γ 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.