title: Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming.
abstract: 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.
authors.affiliation: Ludwig Institute Clinical Trial Center, Columbia University, New York, NY 10032, USA. danila.valmori@univ-nantes.fr
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
authors.forename: Naira E
authors.initials: NE
authors.lastname: Souleimanian
authors.forename: Valeria
authors.initials: V
authors.lastname: Tosello
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
authors.forename: Sylvia
authors.initials: S
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: O'Neill
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.forename: Juliet B
authors.initials: JB
authors.lastname: Escalon
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Cruz
authors.forename: Angelica
authors.initials: A
authors.lastname: Angiulli
authors.forename: Francesca
authors.initials: F
authors.lastname: Angiulli
authors.forename: Gregory
authors.initials: G
authors.lastname: Mears
authors.forename: Susan M
authors.initials: SM
authors.lastname: Vogel
authors.forename: Linda
authors.initials: L
authors.lastname: Pan
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hoffmann
authors.forename: Ralph
authors.initials: R
authors.lastname: Venhaus
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
mesh_terms: 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
chemical_list: 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