Identification of CTL epitopes in novel tumour antigens for immunotherapy in human lung cancer
Identification of CTL epitopes in novel tumour antigens for immunotherapy in human lung cancer
Lung cancer is the commonest cause of cancer death in the developed world. Current treatment options are limited with only 5% of patients alive 5 years from diagnosis. CTL-based immunotherapy, a novel treatment approach, is based on the observation that CD8+ cytotoxic T lymphocytes (CTL) can make an effective response to proteins (antigens) expressed in cancer.
Anti-tumour immunity is a complex interaction of molecular and cellular mechanisms, with CTL (in association with CD4 T cell help) representing the major effector cells capable of producing cell killing. For a candidate tumour antigen to be a suitable target for a vaccine it would ideally have expression restricted to tumour cells, be shared by large numbers of histologically different tumours (without down-regulation or mutation) and be processed and presented by tumour cells and dendritic cells.
Nonamer peptides predicted to bind to HLA-A*0201 were identified from nine candidate tumour antigens. Binding to HLA-A*0201 was determined using a T2 (TAP-deficient) stabilisation assay. Approximately 1/3 of peptides demonstrated no binding to HLA-A*0201. Binding at low and intermediate affinity peptides was enhanced by the substitution of a tyrosine residue at position 1 of the nonamer peptide. Two antigen presentation cell systems (monocyte-derived dendritic cells and CD40L activated B cells) were developed and a comparison made of their potential to prime CTL by assessing antigen density and costimlatory molecules. Peptides shown to bind to HLA-A*0201 were used successfully to prime a CTL response in vitro. One predicted epitope used to prime CTL has not been confirmed by another lab and is the subject of a clinical trial.
University of Southampton
Darby, Angela J
37bf05d2-0075-4a39-9825-988680e8dcab
2004
Darby, Angela J
37bf05d2-0075-4a39-9825-988680e8dcab
Darby, Angela J
(2004)
Identification of CTL epitopes in novel tumour antigens for immunotherapy in human lung cancer.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Lung cancer is the commonest cause of cancer death in the developed world. Current treatment options are limited with only 5% of patients alive 5 years from diagnosis. CTL-based immunotherapy, a novel treatment approach, is based on the observation that CD8+ cytotoxic T lymphocytes (CTL) can make an effective response to proteins (antigens) expressed in cancer.
Anti-tumour immunity is a complex interaction of molecular and cellular mechanisms, with CTL (in association with CD4 T cell help) representing the major effector cells capable of producing cell killing. For a candidate tumour antigen to be a suitable target for a vaccine it would ideally have expression restricted to tumour cells, be shared by large numbers of histologically different tumours (without down-regulation or mutation) and be processed and presented by tumour cells and dendritic cells.
Nonamer peptides predicted to bind to HLA-A*0201 were identified from nine candidate tumour antigens. Binding to HLA-A*0201 was determined using a T2 (TAP-deficient) stabilisation assay. Approximately 1/3 of peptides demonstrated no binding to HLA-A*0201. Binding at low and intermediate affinity peptides was enhanced by the substitution of a tyrosine residue at position 1 of the nonamer peptide. Two antigen presentation cell systems (monocyte-derived dendritic cells and CD40L activated B cells) were developed and a comparison made of their potential to prime CTL by assessing antigen density and costimlatory molecules. Peptides shown to bind to HLA-A*0201 were used successfully to prime a CTL response in vitro. One predicted epitope used to prime CTL has not been confirmed by another lab and is the subject of a clinical trial.
Text
1004226.pdf
- Version of Record
More information
Published date: 2004
Identifiers
Local EPrints ID: 465836
URI: http://eprints.soton.ac.uk/id/eprint/465836
PURE UUID: 6619a287-84e1-4a00-854d-bfdc1f75cc55
Catalogue record
Date deposited: 05 Jul 2022 03:15
Last modified: 16 Mar 2024 20:23
Export record
Contributors
Author:
Angela J Darby
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