Concise reportRelease of clonal block in B cell chronic lymphocytic leukaemia by engagement of co-operative epitopes on CD40
Review articleOpen access
Abstract:

AbstractThe clonal cells of patients with B-chronic lymphocytic leukaemia (B-CLL)—which essentially reside in a resting configuration—are characterised by a relative refractoriness to the normal signals for B cell growth and differentiation. Previously it has been shown that, using an in vitro culture system where CD40 is hyper-crosslinked by monoclonal antibody (mAb) held on CD32-transfected mouse L cells, the clonal block in B-CLL cells can be released with a resultant high rate of DNA synthesis ensuing. In the present study, we report that such release can be achieved purely with soluble reagents whereby co-operative epitopes on CD40 are targeted by the combined use of mAb and soluble recombinant CD40L. Substantial levels of DNA synthesis were induced under such conditions in 718 patients using CD40-targeted reagents alone and in 1618 patients in the additional presence of interleukin 4. Possible extrapolation of these findings to novel therapeutic modalities could be envisaged.

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