Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen
Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen
DNA vaccines can activate immunity against tumor Ags expressed as MHC class I-associated peptides. However, priming of CD8+ CTL against weak tumor Ags may require adjuvant molecules. We have used a pathogen-derived sequence from tetanus toxin (fragment C (FrC)) fused to tumor Ag sequences to promote Ab and CD4+ T cell responses. For induction of CD8+ T cell responses, the FrC sequence has been engineered to remove potentially competitive MHC class I-binding epitopes and to improve presentation of tumor epitopes.
The colon carcinoma CT26 expresses an endogenous retroviral gene product, gp70, containing a known H2-Ld-restricted epitope (AH1). A DNA vaccine encoding gp70 alone was a poor inducer of CTL, and performance was not significantly improved by fusion of full-length FrC. However, use of a minimized domain of FrC, with the AH1 sequence fused to the 3' position, led to rapid induction of high levels of CTL. IFN-?-producing epitope-specific CTL were detectable ex vivo and these killed CT26 targets in vitro. The single epitope vaccine was more effective than GM-CSF-transfected CT26 tumor cells in inducing an AH1-specific CTL response and equally effective in providing protection against tumor challenge.
Levels of AH1-specific CTL in vivo were increased following injection of tumor cells, and CTL expanded in vitro were able to kill CT26 cells in tumor bearers. Pre-existing immunity to tetanus toxoid had no effect on the induction of AH1-specific CTL. These data demonstrate the power of epitope-specific CTL against tumor cells and illustrate a strategy for priming immunity via a dual component DNA vaccine.
3908-3913
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
Buchan, Sarah
9ade187d-f127-45de-ad90-9d544d64718a
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
1 October 2002
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
Buchan, Sarah
9ade187d-f127-45de-ad90-9d544d64718a
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Rice, Jason, Buchan, Sarah and Stevenson, Freda K.
(2002)
Critical components of a DNA fusion vaccine able to induce protective cytotoxic T cells against a single epitope of a tumor antigen.
Journal of Immunology, 169 (7), .
Abstract
DNA vaccines can activate immunity against tumor Ags expressed as MHC class I-associated peptides. However, priming of CD8+ CTL against weak tumor Ags may require adjuvant molecules. We have used a pathogen-derived sequence from tetanus toxin (fragment C (FrC)) fused to tumor Ag sequences to promote Ab and CD4+ T cell responses. For induction of CD8+ T cell responses, the FrC sequence has been engineered to remove potentially competitive MHC class I-binding epitopes and to improve presentation of tumor epitopes.
The colon carcinoma CT26 expresses an endogenous retroviral gene product, gp70, containing a known H2-Ld-restricted epitope (AH1). A DNA vaccine encoding gp70 alone was a poor inducer of CTL, and performance was not significantly improved by fusion of full-length FrC. However, use of a minimized domain of FrC, with the AH1 sequence fused to the 3' position, led to rapid induction of high levels of CTL. IFN-?-producing epitope-specific CTL were detectable ex vivo and these killed CT26 targets in vitro. The single epitope vaccine was more effective than GM-CSF-transfected CT26 tumor cells in inducing an AH1-specific CTL response and equally effective in providing protection against tumor challenge.
Levels of AH1-specific CTL in vivo were increased following injection of tumor cells, and CTL expanded in vitro were able to kill CT26 cells in tumor bearers. Pre-existing immunity to tetanus toxoid had no effect on the induction of AH1-specific CTL. These data demonstrate the power of epitope-specific CTL against tumor cells and illustrate a strategy for priming immunity via a dual component DNA vaccine.
Text
3908.pdf
- Version of Record
Restricted to Repository staff only
Request a copy
More information
Published date: 1 October 2002
Identifiers
Local EPrints ID: 26570
URI: http://eprints.soton.ac.uk/id/eprint/26570
ISSN: 0022-1767
PURE UUID: 7a063961-f507-49ed-9ff9-0ac338a70f16
Catalogue record
Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 02:54
Export record
Contributors
Author:
Jason Rice
Author:
Sarah Buchan
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics