Methods of treating neoplastic, autoimmune and inflammatory diseases

Abstract

Methods of treating cancer and autoimmune and inflammatory diseases are provided.

1 - 59 . (canceled) 
     
     
         60 . A method of treating a patient having a CD33-negative cancer with involved non-malignant effector cells, comprising administering to the patient an effective regimen of a CD33 binding agent, whereby progression of the cancer is reduced or the tumor burden is reduced. 
     
     
         61 . The method of  claim 60 , wherein the cancer is selected from the group consisting of CD33-negative acute lymphoid leukemia, CD33-negative chronic lymphoid leukemia, erythrocytic leukemia and megakaryoblastic leukemia, and other CD33-negative hematological malignancies. 
     
     
         62 . The method of  claim 60 , wherein the CD33 binding agent decreases the number of involved non-malignant effector cells, and/or decreases the levels of one or more inflammatory cytokines, chemokines or growth factors, in the patient. 
     
     
         63 . The method of  claim 60 , further comprising monitoring the levels of one or more inflammatory cytokines, chemokines or growth factors and/or the number of involved non-malignant effector cells in the patient. 
     
     
         64 . The method of  claim 63 , wherein the one or more inflammatory cytokines, chemokines or growth factors are interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-1 (MCP-1), RANTES, interleukin-10 (IL-10), interleukin-12 (IL-12), matrix metalloproteinase 2 (MMP2), IP-10 and/or macrophage inflammatory protein 1α (MIP1α) 
     
     
         65 . The method of  claim 63 , further comprising adjusting the dosage of CD33 binding agent based on the monitoring. 
     
     
         66 . The method of  claim 60 , wherein the non-malignant effector cells are monocytes, macrophages, dendritic cells and/or neutrophils. 
     
     
         67 . The method of  claim 66 , wherein the macrophages are tumor-associated macrophages. 
     
     
         68 . The method of  claim 60 , wherein the CD33 binding agent is administered in combination with at least one therapeutic agent effective against the cancer. 
     
     
         69 . The method of  claim 68 , wherein the therapeutic agent is a chemotherapeutic agent, a radiotherapeutic agent, a therapeutic antibody, an antisense or siRNA drug, a small molecule drug, or a peptide drug. 
     
     
         70 . The method of  claim 69 , wherein the therapeutic agents is a chemotherapeutic agent. 
     
     
         71 . The method of  claim 70 , wherein the chemotherapeutic agent is Velcade® (bortezomib), Revlimid® (lenalidomide), Vidaza® (azacytidine), or cytarabine. 
     
     
         72 . The method of  claim 60 , wherein the CD33 binding agent is an unconjugated antibody that specifically binds to CD33. 
     
     
         73 . The method of  claim 72 , wherein the antibody competes with M195 antibody for specific binding to CD33. 
     
     
         74 . The method of  claim 73 , wherein the antibody is a humanized or chimeric M195 antibody. 
     
     
         75 . The method of  claim 74 , wherein the antibody is administered to the patient intravenously at a dose of 2.5 to about 12 mg/kg. 
     
     
         76 . A method of treating a patient having a cancer-associated cachexia, comprising administering to the patient an effective regimen of a CD33 binding agent, whereby at least one symptom of the cancer-associated cachexia is reduced 
     
     
         77 . The method of  claim 76 , wherein the patent has a CD33 negative cancer. 
     
     
         78 . The method of  claim 76 , wherein the method further comprises monitoring the extent of cancer-associated cachexia responsive to the administration. 
     
     
         79 . The method of  claim 76 , wherein the CD33 binding agent is an unconjugated antibody that specifically binds to CD33. 
     
     
         80 . The method of  claim 79 , wherein the antibody competes with M195 antibody for specific binding to CD33. 
     
     
         81 . The method of  claim 80 , wherein the antibody is a humanized or chimeric M195 antibody. 
     
     
         82 . The method of  claim 81 , wherein the antibody is administered to the patient intravenously at a dose of 2.5 to about 12 mg/kg. 
     
     
         83 . A method of delaying progression of a non-hematological malignancy, comprising administering to a patient with a non-hematological malignancy an effective regimen of a CD33 binding agent and thereby delaying progression of the non-hematological malignancy. 
     
     
         84 . The method of  claim 83 , wherein the CD33 binding agent is an unconjugated antibody that specifically binds to CD33. 
     
     
         85 . The method of  claim 84 , wherein the antibody competes with M195 antibody for specific binding to CD33. 
     
     
         86 . The method of  claim 85 , wherein the antibody is a humanized or chimeric M195 antibody. 
     
     
         87 . The method of  claim 86 , wherein the antibody is administered to the patient intravenously at a dose of 2.5 to about 12 mg/kg. 
     
     
         88 . A method of treating a patient having an autoimmune or inflammatory disease with involved non-malignant effector cells, comprising administering to the patient an effective regimen of a CD33 binding agent, whereby at least one symptom of the disease is reduced. 
     
     
         89 . The method of  claim 88 , wherein the CD33 binding agent is an unconjugated antibody that specifically binds to CD33. 
     
     
         90 . The method of  claim 89 , wherein the antibody competes with M195 antibody for specific binding to CD33. 
     
     
         91 . The method of  claim 90 , wherein the antibody is a humanized or chimeric M195 antibody. 
     
     
         92 . The method of  claim 91 , wherein the antibody is administered to the patient intravenously at a dose of 2.5 to about 12 mg/kg. 
     
     
         93 . The method of  claim 88 , wherein the CD33 binding agent decreases the number of involved non-malignant effector cells and/or decreases the levels of one or more inflammatory cytokines, chemokines or growth factors, in the patient. 
     
     
         94 . The method of  claim 93 , further comprising monitoring the levels of one or more inflammatory cytokines, chemokines or growth factors and/or monitoring the number of involved non-malignant effector cells in the patient. 
     
     
         95 . The method of  claim 94 , wherein the one or more inflammatory cytokines, chemokines or growth factors are interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-1 (MCP-1), RANTES, interleukin-10 (IL-10), interleukin-12 (IL-12), matrix metalloproteinase 2 (MMP2), IP-10 and/or macrophage inflammatory protein 1α (MIP1α). 
     
     
         96 . The method of  claim 95 , further comprising adjusting the dosage of CD33 binding agent based on the monitoring. 
     
     
         97 . The method of  claim 95 , wherein the non-malignant effector cells are monocytes, macrophages, dendritic cells and/or neutrophils. 
     
     
         98 . The method of  claim 88 , wherein the CD33 binding agent is administered in combination with at least one therapeutic agent effective against the autoimmune or inflammatory disease. 
     
     
         99 . The method of  claim 88 , wherein the autoimmune or inflammatory disease is inflammatory bowel disease, psoriasis, atopic dermatitis, psoriatic arthritis, rheumatoid arthritis or atopic dermatitis.