In vivo binding of mouse IgG via polyreactive surface IgM abrogates progressive lymphocytosis in prolymphocytic leukemia.
Surface IgM expressed by malignant CD5+ B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) has previously been shown to bind mouse Ig in what appears to be an example of polyreactive antigen-binding activity. This report demonstrates the in vitro and in vivo binding of mouse Ig to the surface of malignant B-cells from a patient with B-cell prolymphocytic leukemia (B-PLL). In vitro studies showed that K121, a mouse monoclonal antibody, bound to the B-PLL cells via the same low-affinity binding interaction demonstrated to occur between mouse Ig and surface IgM expressed by B-CLL cells rather than in the conventional sense against a specific antigen via its antigen-binding site. With the view to using this phenomenon to target malignant B-cells, it was important to determine whether the low-affinity interaction also occurred in vivo. Infusions of K121 totalling 286 mg were administered to a B-PLL patient over 7 days. Binding of K121 to circulating B-PLL cells was demonstrable after the administration of 36 mg of antibody and was preceded by the appearance of free antibody in the serum. Throughout the period of the infusion, the rapid rise in the peripheral blood white cell count normally observed after leukopheresis was abrogated. However, the count rose markedly after cessation of the antibody infusion in parallel with a decrease in both free and cell-bound K121. There were no observable side effects and no host immune response to either species specific or idiotypic determinants on the mouse Ig was detected. The in vivo binding of mouse Ig together with the previous in vitro data suggest the potential for a novel targeting mechanism using a region of the mouse Ig molecule to target polyreactive Ig expressed by malignant cells in B-CLL and B-PLL.
Weston
K M
KM
Department of Cell and Molecular Biology, University of Technology, Sydney, NSW, Australia. kath.weston@uts.edu.au
Mulligan
S P
SP
Raison
R L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015463:Leukemia, Prolymphocytic / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D008218:Lymphocytosis / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D010641:Phenotype
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G