Open AccessRecombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans
Author(s) -
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 A. McArthur,
Duncan MacGregor,
Sue Sturrock,
Tsin Yee Tai,
Simon Green,
Andrew G. S. Cuthbertson,
Darryl Maher,
Lena Miloradovic,
Susan V Mitchell,
Gerd Ritter,
Achim A. Jungbluth,
Yao Tseng Chen,
Sacha Gnjatic,
Eric W. Hoffman,
Lloyd J. Old,
Jonathan Cebon
Publication year - 2004
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0403572101
Subject(s) - adjuvant , immunogenicity , epitope , antigen , immunology , antibody , cd8 , cancer vaccine , recombinant dna , medicine , titer , immunity , immunotherapy , virology , immune system , biology , biochemistry , gene
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.