The aberrant activation of B cells plays a central role
in the pathogenesis of various autoimmune diseases
and B-cell lymphomas. Now, Honigberg and
colleagues describe an orally available, potent and
selective inhibitor of the B-cell receptor (BCR)
signalling molecule Bruton's tyrosine kinase (BTK), which shows promising
activity in mouse models of autoimmunity and in spontaneously occuring
B-cell lymphomas in dogs.
BTK is a well-defined downstream component of the BCR signalling cascade
with an essential role in B-cell development and activation. BTK mutations in
humans cause X-linked agammaglobulinaemia, which is characterized by
severe B cell-specific defects including the complete absence of B cells in the
periphery. Clinical studies with rituximab, a regulatory approved
CD20-specific monoclonal antibody, have shown that B-cell depletion is
efficacious in autoimmune diseases such as rheumatoid arthritis. Rituximab
is also approved for the treatment of non-Hodgkin's lymphoma (NHL).
Nature Reviews Drug Discovery 9, 681 (September 2010) |
doi:10.1038/nrd3262
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