CD8 T-cell recognition of human 5T4 oncofetal antigen

Lucy J.C. Smyth, Eyad Elkord, Taher E.I. Taher, Hui Rong Jiang, Deborah J. Burt, Alison Clayton, Peter A. Van Veelen, Arnoud De Ru, Ferry Ossendorp, Cornelis J.M. Melief, Jan W. Drijfhout, Said Dermime, Robert E. Hawkins, Peter L. Stern

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas, including colorectal, ovarian and gastric carcinomas. The restricted expression of 5T4 on tumor tissues as well as its implication in tumor progression and bad prognosis makes 5T4 a promising new candidate for immunotherapy. An MVA vaccine encoding 5T4 antigen has been successfully evaluated in preclinical studies in a murine tumor model. Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4). Analysis of several donors confirms a repertoire of such CD8 responses. In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen. Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFNγ ELISPOT. Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFNγ ELISPOT or ELISA. Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response. In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.

Original languageEnglish
Pages (from-to)1638-1647
Number of pages10
JournalInternational Journal of Cancer
Volume119
Issue number7
DOIs
Publication statusPublished - 1 Oct 2006
Externally publishedYes

Fingerprint

T-Lymphocytes
Enzyme-Linked Immunospot Assay
Epitopes
Antigens
Peptides
Neoplasms
Peptide T
Proteasome Endopeptidase Complex
Adenoviridae
Immunotherapy
Monocytes
Digestion
Colorectal Neoplasms
Stomach
Complementary DNA
Enzyme-Linked Immunosorbent Assay
oncofetal antigens
Carcinoma
HLA-A*02:01 antigen

Keywords

  • 5T4 oncofetal antigen
  • Adenovirus
  • CD8 T cells
  • Dendritic cells
  • Proteasome

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Smyth, L. J. C., Elkord, E., Taher, T. E. I., Jiang, H. R., Burt, D. J., Clayton, A., ... Stern, P. L. (2006). CD8 T-cell recognition of human 5T4 oncofetal antigen. International Journal of Cancer, 119(7), 1638-1647. https://doi.org/10.1002/ijc.22018

CD8 T-cell recognition of human 5T4 oncofetal antigen. / Smyth, Lucy J.C.; Elkord, Eyad; Taher, Taher E.I.; Jiang, Hui Rong; Burt, Deborah J.; Clayton, Alison; Van Veelen, Peter A.; De Ru, Arnoud; Ossendorp, Ferry; Melief, Cornelis J.M.; Drijfhout, Jan W.; Dermime, Said; Hawkins, Robert E.; Stern, Peter L.

In: International Journal of Cancer, Vol. 119, No. 7, 01.10.2006, p. 1638-1647.

Research output: Contribution to journalArticle

Smyth, LJC, Elkord, E, Taher, TEI, Jiang, HR, Burt, DJ, Clayton, A, Van Veelen, PA, De Ru, A, Ossendorp, F, Melief, CJM, Drijfhout, JW, Dermime, S, Hawkins, RE & Stern, PL 2006, 'CD8 T-cell recognition of human 5T4 oncofetal antigen', International Journal of Cancer, vol. 119, no. 7, pp. 1638-1647. https://doi.org/10.1002/ijc.22018
Smyth LJC, Elkord E, Taher TEI, Jiang HR, Burt DJ, Clayton A et al. CD8 T-cell recognition of human 5T4 oncofetal antigen. International Journal of Cancer. 2006 Oct 1;119(7):1638-1647. https://doi.org/10.1002/ijc.22018
Smyth, Lucy J.C. ; Elkord, Eyad ; Taher, Taher E.I. ; Jiang, Hui Rong ; Burt, Deborah J. ; Clayton, Alison ; Van Veelen, Peter A. ; De Ru, Arnoud ; Ossendorp, Ferry ; Melief, Cornelis J.M. ; Drijfhout, Jan W. ; Dermime, Said ; Hawkins, Robert E. ; Stern, Peter L. / CD8 T-cell recognition of human 5T4 oncofetal antigen. In: International Journal of Cancer. 2006 ; Vol. 119, No. 7. pp. 1638-1647.
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