Multiepitope CD8(+) T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting
Details
Serval ID
serval:BIB_DAE7405F50E4
Type
Article: article from journal or magazin.
Publication sub-type
Letter (letter): Communication to the publisher.
Collection
Publications
Institution
Title
Multiepitope CD8(+) T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting
Journal
Journal of Clinical Investigation
ISSN
0021-9738 (Print)
Publication state
Published
Issued date
12/2002
Volume
110
Number
12
Pages
1813-22
Notes
Comment
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Abstract
The cancer-testis antigen NY-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8(+) T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8(+) T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8(+) T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1(+) tumor cells. In contrast, the majority of peptide 157-165-specific CD8(+) T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8(+) T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize NY-ESO-1-expressing tumor targets. Thus, because of the complexity of the CD8(+) T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.
Keywords
Antigens, Neoplasm/*immunology
CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism
Cancer Vaccines/*immunology/metabolism
Cells, Cultured
Epitopes/immunology/*metabolism
HLA-A2 Antigen/immunology/metabolism
Humans
Leiomyosarcoma/immunology/therapy
Male
*Membrane Proteins
Neoplasms/*immunology/therapy
Protein Binding
Proteins/*immunology
Sarcoma, Synovial/immunology/therapy
Vaccines, Subunit/*immunology/therapeutic use
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:14
Last modification date
20/08/2019 17:00