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

Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigen s 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-l-expressing tumo rs. A clinical trial was initiated to study the immunological effects of in tradermal vaccination with 3 HLA-AZ-binding NY-ESO-1 peptides in 12 patient s with metastatic NY-ESO-l-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody po sitive at the outset of the study. Primary peptide-specific CD8+ T-cell rea ctions and delayed-type hypersensitivity responses were generated in four o f 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 asso ciated with disease stabilization and objective regression of single metast ases. NY-ESO-1 antibody-positive patients did not develop significant chang es in baseline NY-ESO-1-specific T-cell reactivity, However, stabilization of disease and regression of individual metastases were observed in three o f five immunized patients. These results demonstrate that primary NY-ESO-1- specific CD8+ T-cell responses can be induced by intradermal immunization w ith NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the pot ential to alter the natural course of NY-ESO-1-expressing tumors.