Therapeutic agents as cytokine antagonists and agonists

Abstract

A therapeutic agent capable of of binding to the F′-G′ loop of domain 4 of the common c Chain of the receptor for GM-CSF, IL-3, and IL-5. The amino acid Tyr 421 which is located in the F′-G′ loop is critical in the high affinity binding and stimulation of function of GM-CSF, IL-3 and IL-5 to the common c chain of the receptors. Other receptors for cytokines also show hydrophobic amino acids in analogous positions and it is probable that they too play a pivotal role in binding of respective cytokines to them and in modulating function. Agents capable of binding to the F′-G′ loops are suggested and should be of therapeutic value.

1. An antibody or fragment thereof that binds to SEQ ID NO:  1  present in the common β c  chain of the receptor for GM-CSF, IL-3 and IL- 5, said common β   c  chain having the amino acid sequence set forth in SEQ ID NO:1,  wherein said antibody or fragment thereof antagonizes the effects of at least one cytokine selected from the group consisting of GM-CSF, IL- 3 or  and  IL-5 by inhibiting the binding of the cytokine to the common β c  chain. 
     
     
       2. An antibody or fragment thereof  according to  claim 1  which binds to Tyr 421   Tyr of SEQ ID NO:1 of the common β c  chain of the receptor for GM-CSF, IL-3 and IL-5. 
     
     
       3. An antibody or fragment thereof  according to claim  2    1  which inhibits binding between Tyr 421   Tyr of SEQ ID NO:1 of the common β c  chain and any one of GM-CSF, IL-3 and IL-5. 
     
     
       4. An antibody or fragment thereof according to claim  2    1  which inhibits binding between Tyr 421   Tyr of SEQ ID NO:1 of the common β c  chain and all of  GM-CSF, IL-3 and IL-5. 
     
     
       5. An antibody or fragment thereof according to claim  2    1  wherein the cytokine  receptor is selected from the group consisting of GM-CSFR, IL-5R and IL-3R.