Lentivector immunization induces tumor antigen-specific B and T cell responses in vivo.
Expression of the cancer/germ-line antigen NY-ESO-1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY-ESO-1 (rLV/ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA-A2-transgenic mice elicited long-lasting B and T cell responses against NY-ESO-1. CD8+ T cells against the HLA-A2-restricted peptide NY-ESO-1(157-165) were readily detectable ex vivo and showed restricted TCR Vbeta usage. Moreover, rLV/ESO elicited a far greater anti-NY-ESO-1(157-165) CD8+ T cell response than peptide- or protein-based vaccines. Anti-NY-ESO-1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen-specific CD8+ T cells. The rLV/ESO also induced CD4+ T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8+ T cell responses against NY-ESO-1. The induced CD4+ T cells were primarily directed against a single NY-ESO-1 epitope spanning amino acids 81-100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo.
Ludwig Institute for Cancer Research-Lausanne Branch, University of Lausanne, Chemin des Boveresses 155, Epalinges, Switzerland.
Javier
J
Garcia Casado
Jozef
J
Janda
Joe
J
Wei
Laurence
L
Chapatte
Sara
S
Colombetti
Pedro
P
Alves
Gerd
G
Ritter
Maha
M
Ayyoub
Danila
D
Valmori
Weisan
W
Chen
Frédéric
F
Lévy
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D016086:Lentivirus; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic