Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
Identifieur interne : 002A68 ( Main/Exploration ); précédent : 002A67; suivant : 002A69Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
Auteurs : Ashley J. Knights [Suisse] ; Natko Nuber [Suisse] ; Christopher W. Thomson [Suisse] ; Olga De La Rosa [Suisse] ; Elke J Ger [Allemagne] ; Jean-Marie Tiercy [Suisse] ; Maries Van Den Broek [Suisse] ; Steve Pascolo [Suisse] ; Alexander Knuth [Suisse] ; Alfred Zippelius [Suisse]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2009-03-01.
Descripteurs français
- Wicri :
- topic : Vaccination.
English descriptors
Abstract
Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.
Url:
DOI: 10.1007/s00262-008-0556-8
Affiliations:
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This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Suisse</li></country><region><li>District de Darmstadt</li><li>Hesse (Land)</li></region><settlement><li>Francfort-sur-le-Main</li></settlement></list><tree><country name="Suisse"><noRegion><name sortKey="Knights, Ashley J" sort="Knights, Ashley J" uniqKey="Knights A" first="Ashley J." last="Knights">Ashley J. Knights</name></noRegion><name sortKey="De La Rosa, Olga" sort="De La Rosa, Olga" uniqKey="De La Rosa O" first="Olga" last="De La Rosa">Olga De La Rosa</name><name sortKey="Knights, Ashley J" sort="Knights, Ashley J" uniqKey="Knights A" first="Ashley J." last="Knights">Ashley J. Knights</name><name sortKey="Knuth, Alexander" sort="Knuth, Alexander" uniqKey="Knuth A" first="Alexander" last="Knuth">Alexander Knuth</name><name sortKey="Nuber, Natko" sort="Nuber, Natko" uniqKey="Nuber N" first="Natko" last="Nuber">Natko Nuber</name><name sortKey="Pascolo, Steve" sort="Pascolo, Steve" uniqKey="Pascolo S" first="Steve" last="Pascolo">Steve Pascolo</name><name sortKey="Thomson, Christopher W" sort="Thomson, Christopher W" uniqKey="Thomson C" first="Christopher W." last="Thomson">Christopher W. 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