Multiepitope CD8+ T cell response to an NY-ESO-1 peptide vaccine results in imprecise tumor targeting Journal Article
| Authors: | Dutoit, V.; Taub, R. N.; Papadopoulos, K. P.; Talbot, S.; Keohan, M. L.; Brehm, M.; Gnjatic, S.; Harris, P. E.; Bisikirska, B.; Guillaume, P.; Cerottini, J. C.; Hesdorffer, C. S.; Old, L. J.; Valmori, D. |
| Article Title: | Multiepitope CD8+ T cell response to an NY-ESO-1 peptide vaccine results in imprecise tumor targeting |
| 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: | protein expression; unclassified drug; human cell; case report; cancer adjuvant therapy; binding affinity; protein domain; neoplasms; t lymphocyte; cd8-positive t-lymphocytes; proteins; cells, cultured; granulocyte macrophage colony stimulating factor; protein binding; membrane proteins; tumor antigen; immune response; antigens, neoplasm; cancer vaccine; cancer vaccines; ny eso 1 antigen; antigen recognition; vaccination; epitope; tumor cell; target cell; leiomyosarcoma; synovial sarcoma; sarcoma, synovial; polymer; t lymphocyte subpopulation; vaccines, subunit; hla-a2 antigen; epitopes; synthetic peptide; humans; human; male; priority journal; article |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 110 |
| Issue: | 12 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2002-12-15 |
| Start Page: | 1813 |
| End Page: | 1822 |
| Language: | English |
| DOI: | 10.1172/jci200216428 |
| PUBMED: | 12488431 |
| PROVIDER: | scopus |
| PMCID: | PMC151653 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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