Release of clonal block in B cell chronic lymphocytic leukaemia by engagement of co-operative epitopes on CD40.
The 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 7/18 patients using CD40-targeted reagents alone and in 16/18 patients in the additional presence of interleukin 4. Possible extrapolation of these findings to novel therapeutic modalities could be envisaged.
Department of Haematology, University of Birmingham, Edgbaston, UK.
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Jacob
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JD
Pound
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Challa
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Gordon
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand; D002453:Cell Cycle; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004357:Drug Synergism; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D000939:Epitopes; D008024:Ligands; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D015847:Interleukin-4; D004247:DNA