Variability in B-cell antigen expression: implications for the treatment of B-cell lymphomas and leukemias with monoclonal antibodies.
OBJECTIVE
Antigen expression intensity is becoming important for decision-making in relation to monoclonal antibody therapy. By quantifying CD20, CD22 and CD52 expression on chronic lymphocytic leukemia and normal (control) B cells, over time. The effect of Interleukin-4 therapy on CD20 antigen intensity on B-CLL cells in vivo was also determined.


METHODS
Lymphocytes were purified at weeks 0, 4 and 8 from five B-CLL patients, five healthy volunteers and seven B-CLL patients receiving IL-4 therapy. The number of antigen receptor sites was calculated in molecules of equivalent soluble fluorochrome using flow cytometry.


RESULTS
The mean number of CD20 receptors at baseline was significantly lower on B-CLL cells compared to normal B cells (8160 vs 87 046; P<0.0001). Similar results were obtained for CD22 (8630 vs 27 647; P<0.01), but not for CD52 (371 303 vs 409 484; P = 0.54). When soluble fluorochrome values at weeks 4 and 8 were analysed as change in per cent from baseline (delta%), there was <10 delta% variability in CD20 expression on control B cells, but considerable variability (22.5-67.5 delta%) on B-CLL cells. Expression of CD22 in CLL and control B cells varied by <15 delta%. CD52 on CLL B cells showed slightly greater variability (+/-35 delta%) than that of CD22 (+/-15delta%), but less than that of CD20. IL-4 therapy did not consistently increase the CD20 expression on B-CLL cells in vivo.


CONCLUSIONS
Our data confirm differences in intensity between different target antigens on B-CLL cells, and draws attention to the fact that a substantial variability may occur over time, which may influence clinical decision-making. Caution must be taken when interpreting in vitro results on cytokine-mediated receptor intensity up-regulation.
Rossmann
E D
ED
Department of Oncology (Radiumhemmet), Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
Lundin
J
J
Lenkei
R
R
Mellstedt
H
H
Osterborg
A
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018956:CD5 Antigens / Q000096:biosynthesis; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology; D037102:Lectins; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; C497867:CD22 protein, human; D018956:CD5 Antigens; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D015847:Interleukin-4