NY-ESO-1 is a "cancer-testis" (CT) antigen that is expressed in a wide variety of common cancers. We vaccinated patients with full length NY-ESO-1 protein with and without the ISCOMATRIX™ adjuvant. Immune responses were evaluated by DTH skin testing, antibody assays and cellular assays for epitope-specific CD4+ and CD8+ cells. Antibody titers and DTH reactions were significantly greater in patients who received adjuvant compared to those who received protein alone. Biopsy of DTH lesions showed CD4+ and CD8+ T-cell infiltrates. Antigen-specific T cells capable of recognizing Class I and class II NY-ESO-1 epitopes were isolated from these lesions. Circulating T-cell responses in blood were assessed with tetramers and an intracellular cytokine staining (ICS) assay for IFN-gamma to assess responses to an HLA-A2-restricted epitope NY-ESO-1157-165 (SLLMWITQC). ICS was also employed in a novel assay, which used autologous PBMCs and panels of overlapping peptides. Three of 8 patients who received 100 mg of protein with adjuvant responded to NY-ESO-1157-165. Importantly, responses to a variety of other previously described and undescribed CD4 and CD8 epitopes were seen, demonstrating a broad-based CD4+ and CD8+ cellular immune response against NY-ESO-1. In ongoing work we are defining minimal peptides, mapping these epitopes, and identifying the HLA class I and II restriction for each. Although the study was not designed to evaluate clinical outcomes, data show that those patients who received vaccine with ISCOMATRIX™ adjuvant appeared to have a longer disease-free survival than those who received protein alone or placebo. A prospective evaluation is required to determine whether immune responses to NY-ESO-1 can modify the survival of patients with tumors that express this antigen.
This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
- Copyright © 2003 by Jonathan Cebon