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Cd8 T-cell recognition of human 5T4 oncofetal antigen

Smyth, LJC; Elkord, E; Taher, TEI; Jiang, H; Burt, DJ; Clayton, A; van Veelen, PA; de Ru, A; Ossendorp, F; Melief, CJM; Drijfhout, JW; Dermime, S; Hawkins, RE; Stern, PL

Authors

LJC Smyth

E Elkord

TEI Taher

H Jiang

DJ Burt

A Clayton

PA van Veelen

A de Ru

F Ossendorp

CJM Melief

JW Drijfhout

S Dermime

RE Hawkins

PL Stern



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.

Citation

Smyth, L., Elkord, E., Taher, T., Jiang, H., Burt, D., Clayton, A., …Stern, P. (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

Journal Article Type Article
Publication Date Jan 1, 2006
Deposit Date Dec 23, 2010
Journal International Journal of Cancer
Print ISSN 0020-7136
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 119
Issue 7
Pages 1638-1647
DOI https://doi.org/10.1002/ijc.22018
Publisher URL http://dx.doi.org/10.1002/ijc.22018