Targeted delivery of anti-csf1r antibodies

Abstract

The present disclosure provides compositions and methods for intra-articular delivery of anti-CSF1R antibodies to a tissue that is impacted by a disease that is treatable with CSF1/CSF1R inhibition and/or that expresses CSF1R. It was conventional knowledge that the intra-articular dwell time of proteins in joints is typically a few hours or less. The present disclosure shows, however, that intra-articular delivery of an anti-CSF1R antibody can lead to sustained exposure and pharmacologic activity of the antibody in the joints far beyond a few hours, providing an effective means for targeted and extended delivery of the therapeutic agent.

1 . A method for administering an anti-CSF1R (colony stimulating factor 1 receptor) antibody to a mammalian subject, comprising local administration of a composition comprising the antibody at or proximate to a tissue in the mammalian subject, the tissue is a joint impacted with a tumor, and wherein the tissue comprises at least a cell that expresses CSF1R on the surface. 
     
     
         2 . The method of  claim 1 , wherein the antibody is selected from the group consisting of AM001, emactuzumab, cabiralizumab, axatilimab and IMC-CS4. 
     
     
         3 . The method of  claim 1 , wherein the composition comprises at least 10 mg of the antibody. 
     
     
         4 . The method of  claim 3 , wherein the composition comprises at least 50 mg of the antibody. 
     
     
         5 . The method of  claim 1 , wherein the joint is a knee, elbow, wrist, ankle or hip. 
     
     
         6 . The method of  claim 1 , wherein the local administration is intra-articular injection or intra-tumoral injection. 
     
     
         7 . The method of  claim 6 , wherein the local administration is intraarticular injection. 
     
     
         8 . The method of  claim 1 , wherein the composition further comprises a polymer selected from the group consisting of hyaluronic acid (HA), a poloxamer, alginate, hydroxy methylcellulose (HPMC), hydroxy propylcellulose (HPC), poly(D,L-lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA), a block copolymer comprising hydrophilic poly(ethylene glycol) (PEG) and one or more polymers selected from poly(lactic acid-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and poly(ε-caprolactone-co-glycolic acid) (PCGA), and combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the administration results in sustained exposure of the antibody for at least 3 weeks, 4 weeks, 2 months, 3 months, 4 months, or 6 months. 
     
     
         10 . The method of  claim 1 , wherein the administration is once every 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 6 months, or longer. 
     
     
         11 . The method of  claim 1 , wherein the antibody is AM001. 
     
     
         12 . A method for treating a tumor at a joint in a patient, comprising administering an anti-CSF1R (colony stimulating factor 1 receptor) antibody at or proximate to the joint in the patient. 
     
     
         13 . The method of  claim 12 , wherein the tumor expresses CSF1R on cell surfaces. 
     
     
         14 . The method of  claim 12 , wherein the administering is via intra-articular or intra-tumoral injection. 
     
     
         15 . The method of  claim 12 , wherein the antibody is selected from the group consisting of AM001, emactuzumab, cabiralizumab, axatilimab and IMC-CS4. 
     
     
         16 . The method of  claim 12 , wherein the administration results in sustained exposure of the antibody for at least 3 weeks, 4 weeks, 2 months, 3 months, 4 months, or 6 months. 
     
     
         17 . The method of  claim 12 , wherein the administration is once every 2 weeks, 3 weeks, 4 weeks, 2 months, 3 months, 4 months, 6 months, or longer. 
     
     
         18 . The method of  claim 12 , wherein the antibody is AM001.