Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans.
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.
Davis
Ian D
ID
Ludwig Institute for Cancer Research, Melbourne 3084, Australia. ian.davis@ludwig.edu.au
Chen
Weisan
W
Jackson
Heather
H
Parente
Phillip
P
Shackleton
Mark
M
Hopkins
Wendie
W
Chen
Qiyuan
Q
Dimopoulos
Nektaria
N
Luke
Tina
T
Murphy
Roger
R
Scott
Andrew M
AM
Maraskovsky
Eugene
E
McArthur
Grant
G
MacGregor
Duncan
D
Sturrock
Sue
S
Tai
Tsin Yee
TY
Green
Simon
S
Cuthbertson
Andrew
A
Maher
Darryl
D
Miloradovic
Lena
L
Mitchell
Susan V
SV
Ritter
Gerd
G
Jungbluth
Achim A
AA
Chen
Yao-Tseng
YT
Gnjatic
Sacha
S
Hoffman
Eric W
EW
Old
Lloyd J
LJ
Cebon
Jonathan S
JS
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000939:Epitopes; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D010919:Placebos; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D013737:Testis / Q000473:pathology; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D008565:Membrane Proteins; D010919:Placebos; D011994:Recombinant Proteins; D012503:Saponins