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Immunotherapy of B cell non-Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model

Item Type:Article
Title:Immunotherapy of B cell non-Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model
Creators Name:Panjideh, H. and Mueller, G. and Koch, M. and Wilde, F. and Scheu, S. and Moldenhauer, G. and Lipp, M.
Abstract:Bispecific antibodies are promising agents for immunotherapy. Here we describe a quadroma-based trifunctional bispecific antibody binding the chemokine receptor CXCR5 and the T-cell antigen CD3 that efficiently prevents tumor growth in a mouse B-cell lymphoma model. CXCR5 regulates the tissue homeostasis of mature B-cells and is highly expressed on B-cell non-Hodgkin and lymphocyte-predominant Hodgkin lymphoma, as well as on a subset of CD4 T-cells known as follicular T-helper cells. In vitro, the bispecific CXCR5::CD3 antibody efficiently recruited effector T-cells to CXCR5 expressing B-cells and induced a costimulation-independent activation of CD8(+) and CD4(+) T-cells as demonstrated by the de novo expression of CD25 and CD69, and secretion of the cytokines IFN-γ, TNF-α, IL-6 and IL-10 by peripheral blood mononuclear cells (PBMCs). Notably, at low antibody concentrations CXCR5::CD3-displayed a significantly higher cytotoxic activity against autologous B-cells than its parental antibodies or rituximab. In vivo imaging revealed that CXCR5::CD3 and its parental CXCR5 antibody efficiently prevent tumor growth in a xenograft model of B cell lymphoma in mice and prolong their survival. Taken together, our results identify CXCR5 as a promising target for antibody-based therapies in the treatment of B cell malignancies.
Keywords:Immunotherapy, Bispecific Antibody, Chemokine Receptor, CXCR5, CD3, Non-Hodgkin Lymphoma, Animals, Mice
Source:International Journal of Cancer
Page Range:2623-2632
Date:1 December 2014
Official Publication:https://doi.org/10.1002/ijc.28893
PubMed:View item in PubMed

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