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 formulaAb−Xwhere the group Ab 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.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority under 35 U.S.C § 119(e) to U.S. Provisional Application Ser. No. r 60 / 288,208, filed on May 2, 2001.FIELD OF THE INVENTION[0002]This invention relates to methods for treating and monitoring disease states mediated by activated macrophages. More particularly, ligands that bind to activated macrophages are complexed with an imaging agent, or an immunogen, a cytotoxin or an agent for altering macrophage function for administration to a diseased host for diagnosis and / or treatment of macrophage mediated disease.BACKGROUND AND SUMMARY OF THE INVENTION[0003]The mammalian immune system provides a means for the recognition and elimination of foreign pathogens. While the immune system normally provides a line of defense against foreign pathogens, there are many instances where the immune response itself is involved in the progression of disease. Exemplary of diseases caused or worsened by the host's own immune resp...

AI Technical Summary

Benefits of technology

"The patent text discusses the role of activated macrophages in the immune system and how they can contribute to the progression of disease. Autoimmune diseases like rheumatoid arthritis and lupus erythematosus are caused by the body's own immune response. The text describes the use of folate-linked therapy to target activated macrophages and the folate receptor, which is highly expressed on these cells. The technical effect of this approach is the development of new therapies with reduced toxicity that are effective in treating these diseases."

Problems solved by technology

Activated macrophages nonspecifically engulf and kill foreign pathogens within the macrophage by hydrolytic and oxidative attack resulting in degradation of the pathogen.

The synovial inflammation causes cartilage deterioration and bone erosion with consequent destruction of joint integrity.

The clinical manifestations of RA include pain, swelling, and tenderness in the joints resulting in limitation of motion, weakness, fatigue, and weight loss.

However, these agents have a minimal effect on the progression of the disease and are associated with toxic side effects.

Disease-modifying anti-rheumatic drugs, such as α-penicillamine and sulfasalazine, are also used to treat RA, but the benefit from these drugs is delayed for weeks or months and these drugs have toxic side effects.

Immunosuppressive and cytotoxic drugs suppress symptoms of RA in some patients, but are associated with toxicity.

Preclinical studies with such radioimaging agents have clearly emphasized the value of imaging arthritic tissues in-vivo, however, the selectively of the current imaging agents is not yet optimal, and none of the present compounds is targeted exclusively to activated macrophages.

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