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DNA fusion gene vaccines induce cytotoxic T-cell attack on naturally processed peptides of human prostate-specific membrane antigen

Record type: Article

For long-term attack on tumor cells in patients with prostate cancer, induction of cytolytic T cells is desirable. Several lineage-specific target proteins are known and algorithms have identified candidate MHC class I-binding peptides, particularly for HLA-A*0201. We have designed tolerance-breaking DNA fusion vaccines incorporating a domain of tetanus toxin fused to candidate tumor-derived peptide sequences. Using three separate peptide sequences from prostate-specific membrane antigen (PSMA) (peptides PSMA(27) , PSMA(663) , and PSMA(711) ), this vaccine design induced high levels of CD8(+) T cells against each peptide in a HLA-A(*) 0201 preclinical model. In contrast, the full-length PSMA sequence containing all three epitopes was poorly immunogenic. Induced T cells were cytotoxic against peptide-loaded tumor cells, but only those against PSMA(27) or PSMA(663) peptides, and not PSMA(711) , were able to kill tumor cells expressing endogenous PSMA. Cytotoxicity was also evident in vivo. The preclinical model provides a powerful tool for generating CD8(+) T cells able to predict whether target cells can process and present peptides, essential for planning peptide vaccine-based clinical trials.

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Citation

Vittes, Gisella E., Harden, Elena L., Ottensmeier, Christian H., Rice, Jason and Stevenson, Freda K. (2011) DNA fusion gene vaccines induce cytotoxic T-cell attack on naturally processed peptides of human prostate-specific membrane antigen European Journal of Immunology, 41, (8), pp. 2447-2456. (doi:10.1002/eji.201141518). (PMID:21604260).

More information

e-pub ahead of print date: 4 July 2011
Published date: August 2011
Keywords: antigen presentation/processing, immunotherapy, t cells, vaccination
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 200259
URI: http://eprints.soton.ac.uk/id/eprint/200259
ISSN: 0014-2980
PURE UUID: 6c528fcb-e855-4fff-b88a-11f7108b7d0c

Catalogue record

Date deposited: 24 Oct 2011 14:38
Last modified: 18 Jul 2017 11:14

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Contributors

Author: Gisella E. Vittes
Author: Elena L. Harden
Author: Jason Rice

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