Cancer Immunity 3 Suppl 2:17 (2003)

NY-ESO-1 protein formulated With ISCOMATRIX™ adjuvant induces a broad-based immune response involving high titers of antibody, CD4+ and CD8+ T-cell responses

Jonathan Cebon^1*, Ian D. Davis¹, Weisan Chen¹, Heather Jackson¹, Phillip Parente^1,2, Catherine Barrow^1,2, Wendie Hopkins¹, Qiyuan Chen¹, Roger Murphy¹, Andrew Scott^1,2, Eugene Maraskovsky¹, Grant McArthur³, Duncan MacGregor², Tsin Yee Tai¹, Nektaria Dimopoulos¹, Simon Green⁴, Andrew Cuthbertson⁴, Darryl Maher⁴, Lena Miloradovic⁴, Sue Mitchell⁴, Gerd Ritter⁵, Elisabeth Stockert⁵, Lisa Pugliese⁵, Eric W. Hoffman⁵, and Lloyd J. Old⁵

¹Ludwig Institute for Cancer Research, Melbourne Victoria, Australia
²Austin Hospital
³Peter MacCallum Cancer Centre
⁴CSL Limited
⁵Ludwig Institute for Cancer Research
^*Presenting author

Abstract

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-1_157-165 (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-1_157-165. 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.