title: B and CTL responses to the ALK protein in patients with ALK-positive ALCL.
abstract: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a good prognosis compared to ALK-negative ALCL, possibly as a result of the immune recognition of the ALK proteins. The aim of our study was to investigate the presence of both a B and cytotoxic T cell (CTL) response to ALK in ALK-positive ALCL. We confirmed the presence of an antibody response to ALK in all 9 ALK-positive ALCL patients investigated. An ELISpot assay was used to detect a gamma-interferon (IFN) T cell response after short term culture of mononuclear blood cells with 2 ALK-derived HLA-A*0201 restricted peptides: ALKa and ALKb. A significant gamma-IFN response was identified in all 7 HLA-A*0201-positive ALK-positive ALCL patients but not in ALK-negative ALCL patients (n = 2) or normal subjects (n = 6). CTL lines (>95% CD8-positive) raised from 2 ALK-positive ALCL patients lysed ALK-positive ALCL derived cell lines in a MHC-Class I restricted manner. This is the first report of both a B cell and CTL response to ALK in patients with ALK-positive ALCL. This response persisted during long-term remission. The use of modified vaccinia virus Ankara (MVA) to express ALK is also described. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond to conventional treatment.
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, Leukaemia Research Fund Immunodiagnostics Unit, John Radcliffe Hospital, Oxford, United Kingdom. karen.pulford@ndcls.ox.ac.uk
authors.forename: Kamel
authors.initials: K
authors.lastname: Ait-Tahar
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Christian
authors.initials: C
authors.lastname: Hatton
authors.forename: Tom
authors.initials: T
authors.lastname: Blanchard
authors.forename: Rajko
authors.initials: R
authors.lastname: Kusec
authors.forename: Marion
authors.initials: M
authors.lastname: Becker
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Karen
authors.initials: K
authors.lastname: Pulford
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D007371:Interferon-gamma; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases