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RESEARCH PRODUCT

Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers

Julia RieckenbergMichael ArandDirk JägerJulia KarbachEric W. HoffmanElisabeth StockertGerd RitterYao-tseng ChenYao-tseng ChenElke JägerYasuhiro NagataAlexander KnuthSacha GnjaticLloyd J. OldAntje Neumann

subject

Cytotoxicity ImmunologicMaleAntibodies Neoplasm10050 Institute of Pharmacology and ToxicologyPeptide610 Medicine & healthDiseaseCD8-Positive T-LymphocytesCancer VaccinesAntigenAntigens NeoplasmImmunityTestisHumansMedicineHypersensitivity DelayedAmino Acid Sequencechemistry.chemical_classification1000 MultidisciplinaryMultidisciplinarybusiness.industryMembrane ProteinsProteinsBiological SciencesClinical trialchemistryImmunizationImmunology570 Life sciences; biologyNY-ESO-1PeptidesbusinessCD8

description

Cancer–testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40–50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.

10.5167/uzh-113856https://www.zora.uzh.ch/id/eprint/113856/