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

Hardwick, Nicola; Buchan, Sarah; Ingram, Wendy; Khan, Ghazala; Vittes, Gisella; Rice, Jason; Pulford, Karen; Mufti, Ghulam; Stevenson, Freda; Guinn, Barbara Ann

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. © 2013 by Barbara-ann Guinn.

Citation

Hardwick, N., Buchan, S., Ingram, W., Khan, G., Vittes, G., Rice, J., Pulford, K., Mufti, G., Stevenson, F., & Guinn, B. A. (2013). An analogue peptide from the cancer/testis antigen PASD1 induces CD8+ T cell responses against naturally processed peptide. Cancer Immunology Research, 13(3), 16-26. https://doi.org/10.1158/1424-9634.DCL-16.13.3

• Journal Article Type: Article
• Acceptance Date: Jul 1, 2013
• Online Publication Date: Jul 15, 2013
• Publication Date: Jul 19, 2013
• Deposit Date: Apr 4, 2022
• Publicly Available Date: Oct 27, 2022
• Journal: Cancer Immunology Research
• Print ISSN: 2326-6066
• Electronic ISSN: 2326-6074
• Publisher: American Association for Cancer Research
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 3
• Pages: 16-26
• DOI: https://doi.org/10.1158/1424-9634.DCL-16.13.3
• Keywords: PASD1; immunotherapy; acute myeloid leukemia; DNA vaccine; analogue peptide
• Public URL: https://hull-repository.worktribe.com/output/2596603
• Publisher URL: https://aacrjournals.org/cancerimmun/article/13/3/16/471963/An-analogue-peptide-from-the-Cancer-Testis-antigen