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Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis
Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis
Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6)). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1(126-134) (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1(950-958) epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.
1932-6203
1-19
Brooks, Suzanne E.
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Bonney, Stephanie A.
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Lee, Cindy
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Publicover, Amy
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Khan, Ghazala
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Smits, Evelien L.
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Sigurdardottir, Dagmar
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Arno, Matthew
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Li, Demin
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Mills, Ken I
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Pulford, Karen
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Banham, Alison H
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van Tendeloo, Viggo
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Mufti, Ghulam J
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Rammensee, Hans-Georg
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Elliott, Tim J.
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Orchard, Kim H.
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Guinn, Barbara-ann
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Brooks, Suzanne E.
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Bonney, Stephanie A.
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Lee, Cindy
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Publicover, Amy
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Khan, Ghazala
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Smits, Evelien L.
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Sigurdardottir, Dagmar
099d39ad-5c9c-45cc-8420-763b92b9c3f4
Arno, Matthew
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Li, Demin
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Mills, Ken I
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Pulford, Karen
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Banham, Alison H
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van Tendeloo, Viggo
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Mufti, Ghulam J
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Rammensee, Hans-Georg
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Elliott, Tim J.
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Orchard, Kim H.
794654ab-d6cc-488a-ac11-c9217433c7a2
Guinn, Barbara-ann
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Brooks, Suzanne E., Bonney, Stephanie A., Lee, Cindy, Publicover, Amy, Khan, Ghazala, Smits, Evelien L., Sigurdardottir, Dagmar, Arno, Matthew, Li, Demin, Mills, Ken I, Pulford, Karen, Banham, Alison H, van Tendeloo, Viggo, Mufti, Ghulam J, Rammensee, Hans-Georg, Elliott, Tim J., Orchard, Kim H. and Guinn, Barbara-ann (2015) Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis PLoS ONE, 10, (10), pp. 1-19. (doi:10.1371/journal.pone.0140483). (PMID:18308940).

Record type: Article

Abstract

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6)). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1(126-134) (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1(950-958) epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

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Accepted/In Press date: 25 September 2015
Published date: 22 October 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 395394
URI: http://eprints.soton.ac.uk/id/eprint/395394
ISSN: 1932-6203
PURE UUID: 9fa0b1e7-e74e-49ee-a9c3-6936ba9534cc
ORCID for Tim J. Elliott: ORCID iD orcid.org/0000-0003-1097-0222
ORCID for Kim H. Orchard: ORCID iD orcid.org/0000-0003-2276-3925

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Date deposited: 27 May 2016 14:28
Last modified: 17 Jul 2017 18:54

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Contributors

Author: Suzanne E. Brooks
Author: Stephanie A. Bonney
Author: Cindy Lee
Author: Amy Publicover
Author: Ghazala Khan
Author: Evelien L. Smits
Author: Dagmar Sigurdardottir
Author: Matthew Arno
Author: Demin Li
Author: Ken I Mills
Author: Karen Pulford
Author: Alison H Banham
Author: Viggo van Tendeloo
Author: Ghulam J Mufti
Author: Hans-Georg Rammensee
Author: Tim J. Elliott ORCID iD
Author: Kim H. Orchard ORCID iD
Author: Barbara-ann Guinn

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