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NY-ESO-1 Protein Formulated in ISCOMATRIX Adjuvant Is a Potent Anticancer Vaccine Inducing Both Humoral and CD8⁺ T-Cell-Mediated Immunity and Protection against NY-ESO-1⁺ Tumors

¹ Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre (ARMC), Melbourne, Victoria, Australia;
² CSL Limited, Research & Development, Melbourne,Victoria, Australia;
³ The Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research, Brisbane, Queensland, Australia; and
⁴ Institute Pasteur, Departement-d’Immunologie, Unite d’Immunite Cellulaire Antivirale, Paris, France

NY-ESO-1 is a 180 amino-acid human tumor antigen expressed by many different tumor types and belongs to the family of "cancer-testis" antigens. In humans, NY-ESO-1 is one of the most immunogenic tumor antigens and NY-ESO-1 peptides have been shown to induce NY-ESO-1-specific CD8⁺ CTLs capable of altering the natural course of NY-ESO-1-expressing tumors in cancer patients. Here we describe the preclinical immunogenicity and efficacy of NY-ESO-1 protein formulated with the ISCOMATRIX adjuvant (NY-ESO-1 vaccine). In vitro, the NY-ESO-1 vaccine was readily taken up by human monocyte-derived dendritic cells, and on maturation, these human monocyte-derived dendritic cells efficiently cross-presented HLA-A2-restricted epitopes to NY-ESO-1-specific CD8⁺ T cells. In addition, epitopes of NY-ESO-1 protein were also presented on MHC class II molecules to NY-ESO-1-specific CD4⁺ T cells. The NY-ESO-1 vaccine induced strong NY-ESO-1-specific IFN- and IgG2a responses in C57BL/6 mice. Furthermore, the NY-ESO-1 vaccine induced NY-ESO-1-specific CD8⁺ CTLs in HLA-A2 transgenic mice that were capable of lysing human HLA-A2⁺ NY-ESO-1⁺ tumor cells. Finally, C57BL/6 mice, immunized with the NY-ESO-1 vaccine, were protected against challenge with a B16 melanoma cell line expressing NY-ESO-1. These data illustrate that the NY-ESO-1 vaccine represents a potent therapeutic anticancer vaccine.

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