Document Detail


Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer.
MedLine Citation:
PMID:  17652518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
NY-ESO-1 is a "cancer-testis" antigen expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. The NY-ESO-1 peptide epitope, ESO(157-170), is recognized by HLA-DP4-restricted CD4+ T cells and HLA-A2- and A24-restricted CD8+ T cells. To test whether providing cognate helper CD4+ T cells would enhance the antitumor immune response, we conducted a phase I clinical trial of immunization with ESO(157-170) mixed with incomplete Freund's adjuvant (Montanide ISA51) in 18 HLA-DP4+ EOC patients with minimal disease burden. NY-ESO-1-specific Ab responses and/or specific HLA-A2-restricted CD8+ and HLA-DP4-restricted CD4+ T cell responses were induced by a course of at least five vaccinations at three weekly intervals in a high proportion of patients. There were no serious vaccine-related adverse events. Vaccine-induced CD8+ and CD4+ T cell clones were shown to recognize NY-ESO-1-expressing tumor targets. T cell receptor analysis indicated that tumor-recognizing CD4+ T cell clones were structurally distinct from non-tumor-recognizing clones. Long-lived and functional vaccine-elicited CD8+ and CD4+ T cells were detectable in some patients up to 12 months after immunization. These results confirm the paradigm that the provision of cognate CD4+ T cell help is important for cancer vaccine design and provides the rationale for a phase II study design using ESO(157-170) epitope or the full-length NY-ESO-1 protein for immunotherapy in patients with EOC.
Authors:
Kunle Odunsi; Feng Qian; Junko Matsuzaki; Paulette Mhawech-Fauceglia; Christopher Andrews; Eric W Hoffman; Linda Pan; Gerd Ritter; Jeannine Villella; Bridget Thomas; Kerry Rodabaugh; Shashikant Lele; Protul Shrikant; Lloyd J Old; Sacha Gnjatic
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-08-01     Completed Date:  2007-09-21     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12837-42     Citation Subset:  IM    
Affiliation:
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. kunle.odunsi@@roswellpark.org
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MeSH Terms
Descriptor/Qualifier:
Antibodies / blood,  immunology
Antibody Formation / immunology*
Cancer Vaccines / adverse effects,  immunology*
Female
Freund's Adjuvant / immunology
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class II / immunology*
Humans
Neoplasm Proteins / immunology*
Ovarian Neoplasms / immunology*,  pathology
Peptide Fragments / immunology*
T-Lymphocytes / immunology*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Cancer Vaccines; 0/Histocompatibility Antigens Class I; 0/Histocompatibility Antigens Class II; 0/Neoplasm Proteins; 0/Peptide Fragments; 0/peptide NY-ESO-1 157-170; 9007-81-2/Freund's Adjuvant
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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