Treatment and diagnosis of macrophage mediated disease

Abstract

The invention relates to a method of treating or monitoring/diagnosing a disease state mediated by activated macrophages. The method comprises the step of administering to a patient suffering from a macrophage mediated disease state an effective amount of a composition comprising a conjugate or complex of the general formula A b −X where the group A b comprises a ligand capable of binding to activated macrophages, and when the conjugate is being used for treatment of the disease state, the group X comprises an immunogen, a cytotoxin, or a compound capable of altering macrophage function, and when the conjugate is being used for monitoring/diagnosing the disease state, X comprises an imaging agent. The method is useful for treating a patient suffering from a disease selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, inflammation, infections, osteomyelitis, atherosclerosis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, and systemic sclerosis.

1 .- 19 . (canceled) 
     
     
         20 . A method of treating a disease state mediated by activated macrophages, said method comprising the step of administering to a patient suffering from the macrophage mediated disease state an effective amount of a composition comprising a conjugate of the general formula
   A b −X   
       wherein the group A b  comprises folate, or an analog thereof, wherein folate or the folate analog binds to the folate receptor and is capable of binding to the activated macrophages, and wherein the group X comprises a cytotoxin. 
     
     
         21 . The method of  claim 20  wherein A b  comprises folate. 
     
     
         22 . The method of  claim 20  wherein A b  comprises a folate analog that binds to the folate receptor. 
     
     
         23 . The method of  claim 20  wherein the group X further comprises a liposome. 
     
     
         24 . The method of  claim 20  wherein the patient is suffering from a disease state selected from the group consisting of arthritis, ulcerative colitis, Crohn's disease, inflammatory lesions, infections of the skin, osteomyelitis, organ transplant rejection, pulmonary fibrosis, sarcoidosis, systemic sclerosis, and any chronic inflammation. 
     
     
         25 . The method of  claim 20  further comprising the step of administering to the patient an adjuvant selected from the group consisting of TiterMax Gold, Alum, and GPI-100. 
     
     
         26 . The method of  claim 20  wherein the cytotoxin is selected from the group consisting of a toxin, an alkylating agent, an antimetabolite, a steroid, a platinum compound, a nitrosurea, and a microtubule inhibitor. 
     
     
         27 . The method of  claim 26  wherein the antimetabolite is an antifolate. 
     
     
         28 . The method of  claim 27  wherein the antifolate is methotrexate. 
     
     
         29 . The method of  claim 26  wherein the microtubule inhibitor is selected from the group consisting of vinblastine, vincristine, taxol, and tamoxiphen. 
     
     
         30 . The method of  claim 29  wherein the microtubule inhibitor is vinblastine. 
     
     
         31 . The method of  claim 29  wherein the microtubule inhibitor is taxol. 
     
     
         32 . The method of  claim 26  wherein the steroid is a corticoid. 
     
     
         33 . The method of  claim 32  wherein the corticoid is an adrenocorticoid.