Therapeutic use of anti-CD22 antibodies for inducing trogocytosis

摘要

Disclosed are methods and compositions of anti-B cell antibodies, preferably anti-CD22 antibodies, for diagnosis, prognosis and therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. In certain embodiments, trogocytosis induced by anti-B cell antibodies may determine antibody efficacy, disease responsiveness and prognosis of therapeutic intervention. In other embodiments, optimal dosages of therapeutic antibody may be selected by monitoring the degree of trogocytosis induced by anti-B cell antibodies. Other characteristics of anti-B-cell antibodies that may be monitored include inducing phosphorylation of CD22, CD79a and CD79b; inducing translocation of CD22, CD79a and CD79b to lipid rafts; inducing caspase-dependent apoptosis; increasing pLyn, pERKs and pJNKs; decreasing constitutively-active p38; or inducing mitochondrial membrane depolarization, generation of reactive oxygen species, upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-xl, Mcl-1 and Bcl-2.

主权项

1. A method of treating a human patient with a B-cell malignancy comprising:
a) exposing B cells from the human patient to a chimeric, humanized or human anti-CD22 antibody in vitro in the presence of PBMCs (peripheral blood mononuclear cells) or FcγR-positive cells; b) measuring the depletion of one or more antigens selected from the group consisting of CD19, CD20, CD21, CD22 and CD79b on the surface of the B cells, wherein the antigens are depleted by trogocytosis, to determine the sensitivity of the B cells to the anti-CD22 antibody; and c) administering the anti-CD22 antibody to the human patient, wherein the antibody is capable of inducing trogocytosis of the one or more antigens from the patient's B cells.