Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice.

Sylvie Rusakiewicz (1, 2) , Magalie Dosset (2) , Karine Mollier (3) , Philippe Souque (3) , Pierre Charneau (3) , Simon Wain-Hobson (4) , Pierre Langlade-Demoyen (4) , Olivier Adotévi (2, 4)

1 UMR 1015 - Immunologie des tumeurs et immunothérapie
2 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
3 Virologie moléculaire et Vectorologie
4 Rétrovirologie Moléculaire

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.

Domains: Microbiology and Parasitology

Sylvie Rusakiewicz, Magalie Dosset, Karine Mollier, Philippe Souque, Pierre Charneau, et al.. Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice.. Vaccine, 2010, epub ahead of print. ⟨10.1016/j.vaccine.2010.06.071⟩. ⟨pasteur-00507432⟩