Synergistic anti-cd47 therapy for hematologic cancers

Abstract

Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

1 . A method for the treatment of non-Hodgkin's lymphoma (NHL) in a patient, comprising:
 administering an effective dose of a bispecific FcR-engaging antibody comprising a first variable region selective for (a) CD47; and a second variable region selective for (b) a second NHL associated cell marker;   wherein the first variable region (a) selectively inhibits or blocks CD47 on cancer cells by binding to CD47 on cancer cells and disrupting the interaction between CD47 and SIRPα present on the surface of phagocytic cells; and   the second variable region (b) selectively inhibits or blocks a second NHL associated cell surface marker by binding to the second NHL associated cell surface marker on the cancer cells.   
     
     
         2 . The method of  claim 1 , wherein the NHL is a diffuse large B cell lymphoma. 
     
     
         3 . The method of  claim 1 , wherein said second NHL associated marker is selected from CD20 and CD22. 
     
     
         4 . The method of  claim 2 , wherein said second NHL associated marker is selected from CD20 and CD22. 
     
     
         5 . The method of  claim 1 , wherein the bispecific antibody is conjugated to a cytotoxic agent. 
     
     
         6 . The method of  claim 5 , wherein said cytotoxic agent is selected from the group consisting of a radioactive isotope, a chemotherapeutic agent and a toxin.