Idiotypic vaccination against B cell tumours
Idiotypic vaccination against B cell tumours
Vaccination of BALB/c mice with purified idiotypic IgM derived from the BCL1 lymphoma generates a specific anti-idiotypic response, that is capable of suppressing tumour development. We have analysed the molecular mechanisms involved in the protective response in the BCL1 model. The main mediator of this protection was shown to be antibody. However, anti-idiotypic CD4 positive T cells are presumed to be involved in this antibody production and may have a role in controlling dormant tumour. Spleens have been taken from immune mice and anti-idiotypic T cell lines and hybridomas were generated that proliferate in response to endogenous idiotypic IgM present on the BCL1 cell surface.
Presentation of idiotypic antigen was inhibited by agents that effect metabolism, protein synthesis and proteolytic degradation of antigen in the endosome. This suggests that idiotypic antigen requires endosomal processing to be recognised by anti-idiotypic T cells. Interaction between the presenting B cells and responding T cells was inhibited by anti-Class II and anti-CD4 antibodies, showing that idiotypic antigen is presented to the T cells in the context of MHC class II. Recognition of the tumour was also inhibited by anti-constant region and anti-idiotypic antibodies.
In order to extend this vaccination approach to patients, personal vaccines must be prepared, since idiotypic determinants are unique to each tumour. To facilitate this we are investigating the use of DNA vaccines, in which the variable region genes of immunoglobulin are assembled as single chain Fv (scFv). Initial experiments showed that DNA vaccines encoding scFv alone did induce some anti-idiotypic antibodies, but these were often insufficient and of low titre. By fusing the gene for Fragment C of Tetanus Toxin to the scFv we have promoted the anti-idiotypic antibody response in mice towards levels induced by idiotypic protein.
University of Southampton
King, Catherine Anne
3e310382-3ef1-4d35-ad19-edd82098c2d1
1997
King, Catherine Anne
3e310382-3ef1-4d35-ad19-edd82098c2d1
King, Catherine Anne
(1997)
Idiotypic vaccination against B cell tumours.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Vaccination of BALB/c mice with purified idiotypic IgM derived from the BCL1 lymphoma generates a specific anti-idiotypic response, that is capable of suppressing tumour development. We have analysed the molecular mechanisms involved in the protective response in the BCL1 model. The main mediator of this protection was shown to be antibody. However, anti-idiotypic CD4 positive T cells are presumed to be involved in this antibody production and may have a role in controlling dormant tumour. Spleens have been taken from immune mice and anti-idiotypic T cell lines and hybridomas were generated that proliferate in response to endogenous idiotypic IgM present on the BCL1 cell surface.
Presentation of idiotypic antigen was inhibited by agents that effect metabolism, protein synthesis and proteolytic degradation of antigen in the endosome. This suggests that idiotypic antigen requires endosomal processing to be recognised by anti-idiotypic T cells. Interaction between the presenting B cells and responding T cells was inhibited by anti-Class II and anti-CD4 antibodies, showing that idiotypic antigen is presented to the T cells in the context of MHC class II. Recognition of the tumour was also inhibited by anti-constant region and anti-idiotypic antibodies.
In order to extend this vaccination approach to patients, personal vaccines must be prepared, since idiotypic determinants are unique to each tumour. To facilitate this we are investigating the use of DNA vaccines, in which the variable region genes of immunoglobulin are assembled as single chain Fv (scFv). Initial experiments showed that DNA vaccines encoding scFv alone did induce some anti-idiotypic antibodies, but these were often insufficient and of low titre. By fusing the gene for Fragment C of Tetanus Toxin to the scFv we have promoted the anti-idiotypic antibody response in mice towards levels induced by idiotypic protein.
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Published date: 1997
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Local EPrints ID: 463119
URI: http://eprints.soton.ac.uk/id/eprint/463119
PURE UUID: bc0f7e0f-07d0-421f-abe1-5399baa78751
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Date deposited: 04 Jul 2022 20:45
Last modified: 23 Jul 2022 01:09
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Author:
Catherine Anne King
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