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Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma

Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma
Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma
The clonotypic T-cell antigen receptor (TCR) provides unique V? and Vßsequences with potential as idiotypic targets for immunoregulation. For T-cell malignancies, vaccination with the TCR could induce therapeutic anti-idiotypic responses. To facilitate this approach, we have developed DNA vaccines that include the genes encoding TCR sequences from a T-cell lymphoma (TCL). To combine requirements for stable folding with a simple minimized single-chain construction, we used a three-domain V?VßCß sequence.
To promote anti-TCR immunity, we fused a pathogen-derived sequence from tetanus toxin to the 3'-end of the single-chain TCR. The fusion gene vaccine induced anti-idiotypic antibodies and generated protection against the TCL. The critical requirement for the conformational integrity of the delivered TCR antigen was highlighted by the observation that DNA fusion vaccines containing either V?Vß or VßCß sequences failed to generate antibodies reactive with the native TCR or provide protection. This is the first report of a DNA vaccine able to induce anti-idiotypic immunity against TCL, and it presents a simple strategy for selectively eliminating T-cell clones in vivo.
0008-5472
1757-1760
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Thirdborough, Stephen M.
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Radcliffe, Joanna N.
95bba459-28f5-46d5-b1f1-8e077f115e52
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Thirdborough, Stephen M., Radcliffe, Joanna N., Friedmann, Peter S. and Stevenson, Freda K. (2002) Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma. Cancer Research, 62 (6), 1757-1760.

Record type: Article

Abstract

The clonotypic T-cell antigen receptor (TCR) provides unique V? and Vßsequences with potential as idiotypic targets for immunoregulation. For T-cell malignancies, vaccination with the TCR could induce therapeutic anti-idiotypic responses. To facilitate this approach, we have developed DNA vaccines that include the genes encoding TCR sequences from a T-cell lymphoma (TCL). To combine requirements for stable folding with a simple minimized single-chain construction, we used a three-domain V?VßCß sequence.
To promote anti-TCR immunity, we fused a pathogen-derived sequence from tetanus toxin to the 3'-end of the single-chain TCR. The fusion gene vaccine induced anti-idiotypic antibodies and generated protection against the TCL. The critical requirement for the conformational integrity of the delivered TCR antigen was highlighted by the observation that DNA fusion vaccines containing either V?Vß or VßCß sequences failed to generate antibodies reactive with the native TCR or provide protection. This is the first report of a DNA vaccine able to induce anti-idiotypic immunity against TCL, and it presents a simple strategy for selectively eliminating T-cell clones in vivo.

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Published date: 2002

Identifiers

Local EPrints ID: 27448
URI: http://eprints.soton.ac.uk/id/eprint/27448
ISSN: 0008-5472
PURE UUID: ed2d57e5-3f02-466f-81f2-b2c34467942d
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 28 Apr 2006
Last modified: 20 Jul 2019 01:16

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