Skip to search boxSkip to navigationSkip to main content

An analogue peptide from the cancer testis antigen, PASD1, induces CD8+ T cell-responses against naturally processed peptide

  • Nicola R. Hardwick
    ,
  • Sarah Buchan
    ,
  • Wendy Ingram
    ,
  • Ghazala Khan
    ,
  • Gisella Vittes
    ,
  • Jason Rice
  • King's College London
    ,
  • University of Southampton
    ,
  • University of Oxford
Research Output: Contribution to journal Article Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

We 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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 16-26

Journal (Volume, Issue Number)

Cancer Immunology Research (Volume 13)

Publication milestones

  • Accepted/In press - 29/09/2012
  • Published - 01/01/2013

Publication status

Published - 01/01/2013

ISSN

2326-6066

External Publication IDs

  • handle.net: 10547/578859

Access to documents

Publication metrics

Metrics

Download statistics
Download count
1