Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans

Ian D. Davis, Weisan Chen, Heather Jackson, Phillip Parente, Mark Shackleton, Wendie Hopkins, Qiyuan Chen, Nektaria Dimopoulos, Tina Luke, Roger Murphy, Andrew M. Scott, Eugene Maraskovsky, Grant McArthur, Duncan MacGregor, Sue Sturrock, Tsin Yee Tai, Simon Green, Andrew Cuthbertson, Darryl Maher, Lena MiloradovicSusan V. Mitchell, Gerd Ritter, Achim A. Jungbluth, Yao Tseng Chen, Sacha Gnjatic, Eric W. Hoffman, Lloyd J. Old, Jonathan S. Cebon

Research output: Contribution to journalArticleResearchpeer-review

347 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)10697-10702
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number29
DOIs
Publication statusPublished - 20 Jul 2004

Cite this

Davis, I. D., Chen, W., Jackson, H., Parente, P., Shackleton, M., Hopkins, W., Chen, Q., Dimopoulos, N., Luke, T., Murphy, R., Scott, A. M., Maraskovsky, E., McArthur, G., MacGregor, D., Sturrock, S., Tai, T. Y., Green, S., Cuthbertson, A., Maher, D., ... Cebon, J. S. (2004). Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans. Proceedings of the National Academy of Sciences of the United States of America, 101(29), 10697-10702. https://doi.org/10.1073/pnas.0403572101