System and method for removal of immune inhibitors from biological fluids

Abstract

The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNFα. The system and method are useful for the treatment of different cancer types, stages and severity.

1 - 53 . (canceled) 
     
     
         54 . A system for removing a target component from a body fluid of a patient, the system comprising:
 a sequestering chamber;   an inlet coupled to the sequestering chamber and configured to receive the body fluid; and   a capture support disposed within the sequestering chamber, wherein:
 the capture support comprises a solid support having a tumor necrosis factor (TNF) ligand immobilized thereon; 
 the TNF ligand comprises a modified sequence consisting of a substitution of an amino acid residue in a reference sequence selected from a group of a trimer of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, wherein the monomers are optionally linked by a spacer sequence; and 
 the TNF ligand is configured to bind to the target component. 
   
     
     
         55 . The system of  claim 54 , wherein the reference sequence is one of SEQ ID NO: 2 or SEQ ID NO: 3. 
     
     
         56 . The system of  claim 55 , wherein the reference sequence is SEQ ID NO: 2. 
     
     
         57 . The system of  claim 55 , wherein the reference sequence is SEQ ID NO: 3. 
     
     
         58 . The system of  claim 55 , wherein the reference sequence does not include a spacer sequence. 
     
     
         59 . The system of  claim 54 , wherein the spacer sequence comprises two or more amino acids. 
     
     
         60 . The system of  claim 59 , wherein the spacer sequence comprises a GGGS sequence. 
     
     
         61 . The system of  claim 54 , wherein the target component comprises at least one of sTNF-R1 and sTNF-R2. 
     
     
         62 . The system of  claim 54 , wherein the modified sequence has at least 95% or more identity to the reference sequence. 
     
     
         63 . The system of  claim 62 , wherein the modified sequence has at least 97% or more identity to the reference sequence. 
     
     
         64 . The system of  claim 63 , wherein the modified sequence has at least 98% or more identity to the reference sequence. 
     
     
         65 . The system of  claim 63 , wherein the modified sequence has less than 99% identity to the reference sequence. 
     
     
         66 . The system of  claim 54 , further comprising:
 an access port coupled to the sequestering chamber and configured to facilitate insertion and/or removal of the capture support to or from the sequestering chamber.   
     
     
         67 . The system of  claim 54 , further comprising:
 an outlet coupled to the sequestering chamber and configured to return the body fluid, with a portion of the target component removed, to the patient.