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PMID: 15252201 Published · ppublish English Clinical Trial Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 101 ·No. 29 ·2004-07-20 ·Pages 10697-702

Davis ID, Chen W, Jackson H, Parente P, Shackleton M, Hopkins W, Chen Q, Dimopoulos N, Luke T, Murphy R, Scott AM, Maraskovsky E, McArthur G, MacGregor D, Sturrock S, Tai TY, Green S, Cuthbertson A, Maher D, Miloradovic L, Mitchell SV, Ritter G, Jungbluth AA, Chen YT, Gnjatic S, Hoffman EW, Old LJ, Cebon JS

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.

MeSH Terms
Adjuvants, Immunologic Antibodies, Neoplasm/immunology Antigens, Neoplasm/genetics,immunology CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cancer Vaccines Dose-Response Relationship, Drug Double-Blind Method Epitopes Humans Male Melanoma/immunology,pathology Membrane Proteins/genetics,immunology Placebos Recombinant Proteins/genetics,immunology Saponins/immunology Testis/pathology Treatment Outcome
Chemicals
Adjuvants, Immunologic Antibodies, Neoplasm Antigens, Neoplasm CTAG1B protein, human Cancer Vaccines Epitopes Membrane Proteins Placebos Recombinant Proteins Saponins
Authors & Affiliations
28 authors, click to expand affiliations / ORCID
Davis Ian D
Ludwig Institute for Cancer Research, Melbourne 3084, Australia. [email protected]
Chen Weisan
Jackson Heather
Parente Phillip
Shackleton Mark
Hopkins Wendie
Chen Qiyuan
Dimopoulos Nektaria
Luke Tina
Murphy Roger
Scott Andrew M
Maraskovsky Eugene
McArthur Grant
MacGregor Duncan
Sturrock Sue
Tai Tsin Yee
Green Simon
Cuthbertson Andrew
Maher Darryl
Miloradovic Lena
Mitchell Susan V
Ritter Gerd
Jungbluth Achim A
Chen Yao-Tseng
Gnjatic Sacha
Hoffman Eric W
Old Lloyd J
Cebon Jonathan S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0403572101
Email
[email protected]
Published
2004-07-20
Epub
2004-00-13
Pages
10697-702
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC489997
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.0403572101 PMC Full Text View journal details
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