RELEASE OF CLONAL BLOCK IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA BY ENGAGEMENT OF COOPERATIVE EPITOPES ON CD40

The clonal cells of patients with B-chronic lymphocytic leukaemia (B-C LL)-which essentially reside in a resting configuration-are characteri sed by a relative refractoriness to the normal signals for B cell grow th and differentiation. Previously it has been shown that, using an in vitro culture system where CD40 is hyper-crosslinked by monoclonal an tibody (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 synth esis ensuing. In the present study, we report that such release can be achieved purely with soluble reagents whereby co-operative epitopes o n CD40 are targeted by the combined use of mAb and soluble recombinant CD40L. Substantial levels of DNA synthesis were induced under such co nditions in 7/18 patients using CD40-targeted reagents alone and in 16 /18 patients in the additional presence of interleukin 4. Possible ext rapolation of these findings to novel therapeutic modalities could be envisaged. (C) 1998 Elsevier Science Ltd. All rights reserved.