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dc.contributor.authorHardwick, Nicola R.en
dc.contributor.authorBuchan, Sarahen
dc.contributor.authorIngram, Wendyen
dc.contributor.authorKhan, Ghazalaen
dc.contributor.authorVittes, Gisellaen
dc.contributor.authorRice, Jasonen
dc.contributor.authorPulford, Karenen
dc.contributor.authorMufti, Ghulam J.en
dc.contributor.authorStevenson, Fredaen
dc.contributor.authorGuinn, Barbara-Annen
dc.date.accessioned2015-09-29T08:51:09Zen
dc.date.available2015-09-29T08:51:09Zen
dc.date.issued2013en
dc.identifier.citationHardwick, N.R., Buchan, S., Ingram, W., Khan, G., Vittes, G., Rice, J., Pulford, K., Mufti, G.J., Stevenson, F.K. & Guinn, B.A. (2013) 'An analogue peptide from the cancer testis antigen, PASD1, induces CD8+ T cell-responses against naturally processed peptide'. Cancer Immunity, 13, pp.16-26.en
dc.identifier.issn1424-9634en
dc.identifier.pmid23882161
dc.identifier.urihttp://hdl.handle.net/10547/578859en
dc.description.abstractWe have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in "humanized" mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells.
dc.language.isoenen
dc.publisherCancer Research Instituteen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718735/en
dc.relation.urlhttp://cancerimmunolres.aacrjournals.org/content/canimmarch/13/3/16en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDNA vaccineen
dc.subjectPASD1en
dc.subjectacute myeloid leukemiaen
dc.subjectanalogue peptideen
dc.subjectimmunotherapyen
dc.titleAn analogue peptide from the cancer testis antigen, PASD1, induces CD8+ T cell-responses against naturally processed peptide.en
dc.typeArticleen
dc.contributor.departmentKing’s College Londonen
dc.contributor.departmentUniversity of Southamptonen
dc.contributor.departmentUniversity of Bedfordshireen
dc.contributor.departmentUniversity of Oxforden
dc.identifier.pmcidPMC3718735en
html.description.abstractWe have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in "humanized" mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells.


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