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.
Cancer Sciences Unit (MP824), Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom.
Suzanne E
SE
Brooks
Cancer Sciences Unit (MP824), Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom.
Stephanie A
SA
Bonney
Cancer Sciences Unit (MP824), Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom; Department of Haematology, Southampton University Hospitals Trust, University of Southampton, Southampton, United Kingdom.
Cindy
C
Lee
Department of Haematology, Southampton University Hospitals Trust, University of Southampton, Southampton, United Kingdom.
Amy
A
Publicover
Department of Life Sciences, University of Bedfordshire, Park Square, Luton, United Kingdom.
Ghazala
G
Khan
Laboratory of Experimental Haematology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijkstraat 10, B-2650 Antwerp, Belgium.
Evelien L
EL
Smits
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
Dagmar
D
Sigurdardottir
King's Genomics Centre, School of Biomedical and Health Sciences, King's College London, London, United Kingdom.
Matthew
M
Arno
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Demin
D
Li
Blood Cancer Research Group, Centre for Cancer Research and Cell Biology (CCRCB), Queen's University Belfast, Belfast, United Kingdom.
Ken I
KI
Mills
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Karen
K
Pulford
Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Alison H
AH
Banham
Laboratory of Experimental Haematology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijkstraat 10, B-2650 Antwerp, Belgium.
Viggo
V
van Tendeloo
Department of Haematological Medicine, King's College London School of Medicine, London, United Kingdom.
Ghulam J
GJ
Mufti
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
Hans-Georg
HG
Rammensee
Cancer Sciences Unit (MP824), Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom.
Tim J
TJ
Elliott
Department of Haematology, Southampton University Hospitals Trust, University of Southampton, Southampton, United Kingdom.
Kim H
KH
Orchard
Cancer Sciences Unit (MP824), Somers Cancer Sciences Building, University of Southampton, Southampton, United Kingdom; Department of Life Sciences, University of Bedfordshire, Park Square, Luton, United Kingdom; Department of Haematological Medicine, King's College London School of Medicine, London, United Kingdom.
Barbara-ann
BA
Guinn
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D034961:Antigens, Nuclear / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D015203:Reproducibility of Results
D000951:Antigens, Neoplasm; D034961:Antigens, Nuclear; D000939:Epitopes; C515845:PASD1 protein, human; D010455:Peptides