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Plant viral genes in DNA idiotypic vaccines activate linked CD4+ T-cell mediated immunity against B-cell malignancies

Plant viral genes in DNA idiotypic vaccines activate linked CD4+ T-cell mediated immunity against B-cell malignancies
Plant viral genes in DNA idiotypic vaccines activate linked CD4+ T-cell mediated immunity against B-cell malignancies
DNA delivery of tumor antigens can activate specific immune attack on cancer cells. However, antigens may be weak, and immune capacity can be compromised. Fusion of genes encoding activating sequences to the tumor antigen sequence facilitates promotion and manipulation of effector pathways. Idiotypic determinants of B-cell tumors, encoded by the variable region genes, are clone-specific tumor antigens. When assembled as single-chain Fv (scFv) alone in a DNA vaccine, immunogenicity is low. Previously, we found that fusion of a sequence from tetanus toxin (fragment C; FrC) promoted anti-idiotypic protection against lymphoma and myeloma. We have now investigated an alternative fusion gene derived from a plant virus, potato virus X coat protein, a primary antigen in humans. When fused to scFv, the self-aggregating protein generates protection against lymphoma and myeloma. In contrast to scFv?FrC, protection against lymphoma is mediated by CD4+ T cells, as is protection against myeloma. Plant viral proteins offer new opportunities to activate immunity against linked T-cell epitopes to attack cancer.
1087-0156
760-764
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Munday, Rosalind
283bbfbe-f2a4-4176-ae83-a5d81bc925b6
Spellerberg, Myfanwy B.
c28a2c74-38c0-466b-a143-c88c8a854c9c
Lomonossoff, George P.
896bab6a-3c0c-48e6-9e46-7db6314bbcb6
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Munday, Rosalind
283bbfbe-f2a4-4176-ae83-a5d81bc925b6
Spellerberg, Myfanwy B.
c28a2c74-38c0-466b-a143-c88c8a854c9c
Lomonossoff, George P.
896bab6a-3c0c-48e6-9e46-7db6314bbcb6
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Savelyeva, Natalia, Munday, Rosalind, Spellerberg, Myfanwy B., Lomonossoff, George P. and Stevenson, Freda K. (2001) Plant viral genes in DNA idiotypic vaccines activate linked CD4+ T-cell mediated immunity against B-cell malignancies. Nature Biotechnology, 19 (8), 760-764. (doi:10.1038/90816).

Record type: Article

Abstract

DNA delivery of tumor antigens can activate specific immune attack on cancer cells. However, antigens may be weak, and immune capacity can be compromised. Fusion of genes encoding activating sequences to the tumor antigen sequence facilitates promotion and manipulation of effector pathways. Idiotypic determinants of B-cell tumors, encoded by the variable region genes, are clone-specific tumor antigens. When assembled as single-chain Fv (scFv) alone in a DNA vaccine, immunogenicity is low. Previously, we found that fusion of a sequence from tetanus toxin (fragment C; FrC) promoted anti-idiotypic protection against lymphoma and myeloma. We have now investigated an alternative fusion gene derived from a plant virus, potato virus X coat protein, a primary antigen in humans. When fused to scFv, the self-aggregating protein generates protection against lymphoma and myeloma. In contrast to scFv?FrC, protection against lymphoma is mediated by CD4+ T cells, as is protection against myeloma. Plant viral proteins offer new opportunities to activate immunity against linked T-cell epitopes to attack cancer.

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Published date: 2001

Identifiers

Local EPrints ID: 26593
URI: http://eprints.soton.ac.uk/id/eprint/26593
ISSN: 1087-0156
PURE UUID: c37a2383-d9f3-446f-bdad-d4182080ba7b
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: Rosalind Munday
Author: Myfanwy B. Spellerberg
Author: George P. Lomonossoff

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