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Yu, X.* ; Ilecka, M.* ; Bartlett, E.J.* ; Schneidt, V.* ; Bhat, R.* ; Mautner, J. ; Feederle, R. ; Delecluse, H.J.*

Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen-specific CD4+ T cells.

Blood 125, 1601-1610 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The treatment of non-Hodgkin lymphomas has benefited enormously from the introduction of monoclonal antibody-based therapies. However, the efficacy of these treatments varies with lymphoma subtypes and typically decreases with subsequent relapses. Here, we report on antigen-armed antibodies (AgAbs) as a potential treatment for B-cell lymphoma. AgAbs include antigens from ubiquitous pathogens, such as Epstein-Barr virus (EBV), that persist in their host and elicit strong lifelong T cell responses. They act as vectors by introducing antigen directly into tumor cells to induce an antigen-specific CD4+ T cell response against these cells. We have fused antibodies targeting human B-cell surface receptors (CD19-22) to immunodominant T cell antigens from EBV proteins, including EBNA1, EBNA3B and EBNA3C. Exposure of EBV-transformed B-cells and of BL cells to AgAbs led to antigen presentation, T cell recognition and target cell killing. The efficiency of AgAb action paralleled the abundance of the targeted molecules on lymphoma cells as well as their HLA class II expression levels. AgAbs can also induce the activation and proliferation of EBV-specific memory CD4+ T cells ex vivo. These studies show the potential of AgAbs as an effective therapeutic strategy against B-cell lymphomas.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Epstein-barr-virus; Dendritic Cells; Down-regulation; Infection; Responses; Dec-205; Protein; Rituximab; Receptor; Line
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 125, Issue: 10, Pages: 1601-1610 Article Number: , Supplement: ,
Publisher American Society of Hematology
Publishing Place Washington
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Molecular Immunology (IMI)