Immunotherapy of B‐cell non‐Hodgkin lymphoma by targeting the chemokine receptor CXCR5 in a preclinical mouse model. Issue 11 (29th April 2014)

• Record Type: Journal Article
• Authors: Panjideh, Hossein; Müller, Gerd; Koch, Mathias; Wilde, Frank; Scheu, Susanne; Moldenhauer, Gerhard; Lipp, Martin
• Is Part Of: International journal of cancer. Volume 135:Issue 11(2014:Dec. 01)
• Page Start: 2623
• Page End: 2632
• Publication Date: 2014-04-29
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28893
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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<sup>+</sup> T cells known as follicular T‐helper cells. <italic>In vitro</italic>, the bispecific CXCR5::CD3 antibody efficiently recruited effector T cells to CXCR5 expressing B cells and induced a co‐stimulation‐independent activation of CD8<sup>+</sup> and CD4<sup>+</sup> T cells as demonstrated by the <italic>de novo</italic> expression of CD25 and CD69, and secretion of the cytokines IFN‐γ, TNF‐α, IL‐6 and IL‐10 by peripheral blood mononuclear cells. Notably, at low antibody concentrations, CXCR5::CD3 displayed a significantly higher cytotoxic activity against autologous B cells than its parental antibodies or rituximab. <italic>In vivo</italic> 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.</p> </abstract>