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B and CTL responses to the ALK protein in patients with ALK-positive ALCL

Ait-Taharl, K., Cerundolo, V., Banham, A. H., Hatton, C., Blanchard, T., Kusec, R., Becker, M., Smith, G. L. and Pulford, K. (2006) 'B and CTL responses to the ALK protein in patients with ALK-positive ALCL'. International Journal of Cancer, Vol 118, Issue 3, pp. 688-695.

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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. (c) 2005 Wiley-Liss, Inc.

Item Type: Article
Uncontrolled Keywords: elispot tumour-associated antigens ctl responses alk alcl t-cell responses mhc class-i major histocompatibility complex anaplastic lymphoma kinase melanoma patients tumor-antigen tyrosine kinase antibody-responses myeloid-leukemia hla-a2 melanomas
Subjects: QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General)
QZ Pathology > Neoplasms. Cysts > QZ 200 Neoplasms. Cysts (General)
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
WH Hemic and Lymphatic Systems > Lymphatic System > WH 700 Lymphatic system. Lymphatic diseases (General)
Faculty: Department: Groups (2002 - 2012) > Clinical Group
Digital Object Identifer (DOI): https://doi.org/10.1002/ijc.21410
Depositing User: Martin Chapman
Date Deposited: 14 Apr 2011 11:36
Last Modified: 06 Feb 2018 13:01
URI: http://archive.lstmed.ac.uk/id/eprint/1435

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