Efficient induction of tumor antigen-specific CD8+ memory T cells by recombinant lentivectors.
The success of active cancer immunotherapy entails a robust induction of tumor-reactive effector and memory CD8+ T cells. We compared the in vivo immunogenicity of the melanoma-associated antigen Melan-A(26-35) encoded by third-generation recombinant lentivector (rec. lv) or as peptide admixed with a strong adjuvant. Ex vivo analyses of immunized HLA-A2/H-2K(b) mice showed that rec. lv triggered a stronger anti-Melan-A CD8+ T -cell response than peptide vaccine. Importantly, the majority of anti-Melan-A T cells elicited by rec. lv expressed the memory marker CD127 at the peak of the primary response. In those mice, memory T cells were detectable several months after priming and could be activated by recall peptide vaccination. These results show that immunization with rec. lv induces not only a strong antigen-specific CD8+ T -cell response but also a long-lasting T-cell memory against a bona fide tumor-associated antigen.
Chapatte
Laurence
L
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
Colombetti
Sara
S
Cerottini
Jean-Charles
JC
Lévy
Frédéric
F
D000818:Animals; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000235:genetics; D007156:Immunologic Memory / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments; D012878:Skin Neoplasms / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D010446:Peptide Fragments