Jonathan Cebon
Ludwig Institute for Cancer Research, Melbourne Victoria, Australia

Ian D. Davis¹, Weisan Chen¹, Heather Jackson¹, Phillip Parente¹,², Catherine Barrow¹,², Wendie Hopkins¹, Qiyuan Chen¹, Roger Murphy¹, Andrew Scott¹,², 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, Lloyd J. Old⁵.
¹Ludwig Institute for Cancer Research, Melbourne
² Austin Hospital,
³ Peter MacCallum Cancer Centre,
⁴ CSL Limited,
⁵ Ludwig Institute for Cancer Research

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

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 IFNg 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 PBMC and panels of overlapping peptides. Three of 8 patients who received 100mg 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.