Abstracts (complete list) - Wissenschaft Online

Jörg Rossbacher, Frank Wilde, Gerd Müller, Martin Lipp
CXCR5 as a therapeutic target in Non Hodgkin lymphomas
and autoimmune disease
Homeostatic chemokine receptors and their ligands control the trafficking of
lymphocytes to and within secondary lymphoid organs. The receptor CXCR5 is
expressed on mature recirculating B cells, a subset of memory T cells and follicular B
helper cells (TFH). In cooperation with its ligand, CXCL13, which is expressed on
stromal and follicular dendritic cells in the B cell follicle, CXCR5 is responsible for B/T
separation in lymphoid tissues. It was shown that CXCR5 plays a major role in the
development of secondary lymphoid structures like Peyers Patches and certain lymph
nodes and therefore is suspected to be essential in ectopic follicle formation in chronic
inflammatory diseases like Rheumatoid Arthritis, Sjogren's syndrome and Helicobacter
pylori-induced chronic gastritis.Together with the fact that 90% of B cell non Hodgkin
lymphomas (NHL) express significant levels of CXCR5 on their surface we propose that
CXCR5 is a suitable therapeutic target in B cell NHL and chronic autoimmune disease.
We therefore generated a hybrid hybridoma producing the trifunctional bispecific
antibody bsCXCR5xCD3 to perform CXCR5 positive cell depletion. Bispecificity should
enhance the lytic ability by bringing target and effector cells into close proximity and
the intact Fc portion could attract FcR bearing effector cells or even initiate complement
lysis. We tested the antibody on CXCR5 expressing NHL cell lines and observed
increased cell lysis at various conditions and time points. In addition we tested primay B
cells obtained from healthy human donors and observed efficient cell lysis at
comparable concentrations and time points. These results show that the bispecific
antibody is able to deplete target cells “in vitro”, no matter if they are cancer cell lines
or primary human cells.