Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans
Open Access
- 13 July 2004
- journal article
- clinical trial
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 101 (29), 10697-10702
- https://doi.org/10.1073/pnas.0403572101
Abstract
NY-ESO-1 is a “cancer-testis” antigen expressed in many cancers. ISCOMATRIX is a saponin-based adjuvant that induces antibody and T cell responses. We performed a placebo-controlled clinical trial evaluating the safety and immunogenicity of recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant. Forty-six evaluable patients with resected NY-ESO-1-positive tumors received three doses of vaccine intramuscularly at monthly intervals. The vaccine was well tolerated. We observed high-titer antibody responses, strong delayed-type hypersensitivity reactions, and circulating CD8+ and CD4+ T cells specific for a broad range of NY-ESO-1 epitopes, including known and previously unknown epitopes. In an unplanned analysis, vaccinated patients appeared to have superior clinical outcomes to those treated with placebo or protein alone. The vaccine is safe and highly potent immunologically.Keywords
This publication has 32 references indexed in Scilit:
- A robust human T-cell culture method suitable for monitoring CD8+ and CD4+ T-cell responses from cancer clinical trial samplesJournal of Immunological Methods, 2004
- Liposomes and ISCOMsPublished by Wiley ,2004
- Survey of naturally occurring CD4 + T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responsesProceedings of the National Academy of Sciences, 2003
- CD4+T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: Association with NY-ESO-1 antibody productionProceedings of the National Academy of Sciences, 2001
- Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancersProceedings of the National Academy of Sciences, 2000
- Augmentation of Human Influenza A Virus-Specific Cytotoxic T Lymphocyte Memory by Influenza Vaccine and Adjuvanted Carriers (ISCOMS)Virology, 1999
- Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein.JCI Insight, 1997
- ISCOMs (immunostimulating complexes): The first decadeImmunology & Cell Biology, 1996
- Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphomaNature, 1993
- Detection of intracellular cytokines by flow cytometryJournal of Immunological Methods, 1993