CD8 T-cell recognition of human 5T4 oncofetal antigen

International Journal of Cancer. Journal International Du Cancer
Lucy J C SmythP.L. 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 IFN gamma ELISPOT. Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they exp...Continue Reading

References

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Citations

Nov 16, 2007·Cancer Immunology, Immunotherapy : CII·Eyad ElkordPeter L Stern
Jun 24, 2008·International Immunology·William H ShinglerRichard Harrop
Feb 2, 2008·Neuroimmunomodulation·Ines KaufmannManfred Thiel
Dec 14, 2011·Immunotherapy·Rui-Tao ZhangHoward L Kaufman
Jun 1, 2007·Biomarkers in Medicine·Adam E SnookScott A Waldman
Dec 4, 2009·Expert Review of Anticancer Therapy·Eyad ElkordRobert E Hawkins
Mar 21, 2008·Expert Opinion on Biological Therapy·Eyad ElkordPeter L Stern
Apr 14, 2012·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Saly Al-TaeiZsuzsanna Tabi
Jul 30, 2014·Seminars in Cancer Biology·Peter L SternOwen J McGinn
Oct 9, 2012·Cellular Immunology·Martin ScurrAndrew Godkin
Oct 10, 2007·American Journal of Human Genetics·Geraldine M ClarkeLon R Cardon
Oct 21, 2016·Cancer Immunology, Immunotherapy : CII·Peter L Stern, Richard Harrop
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hui-Rong JiangPeter L Stern
Feb 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christy RalphFiona C Thistlethwaite
Mar 6, 2021·Human Vaccines & Immunotherapeutics·Yuexin XuScott S Tykodi

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