title: Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad antibody responses in humans, a RAYS-based analysis.
abstract: Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that target-specific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen.
authors.affiliation: University Hospital Zurich, Department of Oncology, Rämistr. 100, CH-8091 Zurich, Switzerland. axel.mischo@usz.ch
authors.forename: Axel
authors.initials: A
authors.lastname: Mischo
authors.forename: Nina
authors.initials: N
authors.lastname: Bubel
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Cebon
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Samaras
authors.forename: Ulf
authors.initials: U
authors.lastname: Petrausch
authors.forename: Frank
authors.initials: F
authors.lastname: Stenner-Liewen
authors.forename: Niklaus G
authors.initials: NG
authors.lastname: Schaefer
authors.forename: Boris
authors.initials: B
authors.lastname: Kubuschok
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.forename: Andreas
authors.initials: A
authors.lastname: Wadle
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D002784:Cholesterol / Q000494:pharmacology* / Q000627:therapeutic use; D045142:Cross-Priming / Q000276:immunology; D004338:Drug Combinations; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000628:therapy; D010743:Phospholipids / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D004338:Drug Combinations; D000939:Epitopes; C493786:ISCOMATRIX; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D012503:Saponins; D002784:Cholesterol