Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming.
The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8(+) T cell responses, through in vivo cross-priming, has remained unclear. In this article, we report that repeated vaccination of cancer patients with recombinant NY-ESO-1 protein, Montanide ISA-51, and CpG ODN 7909, a potent stimulator of B cells and T helper type 1 (Th1)-type immunity, resulted in the early induction of specific integrated CD4(+) Th cells and antibody responses in most vaccinated patients, followed by the development of later CD8(+) T cell responses in a fraction of them. The correlation between antibody and T cell responses, together with the ability of vaccine-induced antibodies to promote in vitro cross-presentation of NY-ESO-1 by dendritic cells to vaccine-induced CD8(+) T cells, indicated that elicitation of NY-ESO-1-specific CD8(+) T cell responses by cross-priming in vivo was associated with the induction of adequate levels of specific antibodies. Together, our data provide clear evidence of in vivo cross-priming of specific cytotoxic T lymphocytes by a recombinant tumor antigen vaccine, underline the importance of specific antibody induction for the cross-priming to occur, and support the use of this type of formulation for the further development of efficient cancer vaccines.
Valmori
Danila
D
Ludwig Institute Clinical Trial Center, Columbia University, New York, NY 10032, USA. danila.valmori@univ-nantes.fr
Souleimanian
Naira E
NE
Tosello
Valeria
V
Bhardwaj
Nina
N
Adams
Sylvia
S
O'Neill
David
D
Pavlick
Anna
A
Escalon
Juliet B
JB
Cruz
Crystal M
CM
Angiulli
Angelica
A
Angiulli
Francesca
F
Mears
Gregory
G
Vogel
Susan M
SM
Pan
Linda
L
Jungbluth
Achim A
AA
Hoffmann
Eric W
EW
Venhaus
Ralph
R
Ritter
Gerd
G
Old
Lloyd J
LJ
Ayyoub
Maha
M
D000906:Antibodies / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000009:adverse effects / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D008353:Mannitol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D008565:Membrane Proteins / Q000009:adverse effects / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009829:Oleic Acids / Q000009:adverse effects / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D009838:Oligodeoxyribonucleotides / Q000009:adverse effects / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination
D000906:Antibodies; D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D008565:Membrane Proteins; D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; C477385:montanide ISA 51; D008353:Mannitol