US2021260111A1PendingUtilityA1

Methods for generating macrophages with enhanced cancer phagocytosis

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Assignee: UNIV GEORGIA STATE RES FOUNDPriority: Apr 10, 2016Filed: May 10, 2021Published: Aug 26, 2021
Est. expiryApr 10, 2036(~9.7 yrs left)· nominal 20-yr term from priority
Inventors:Yuan LiuZhen BianKe Zen
A61K 38/19A61K 40/416A61K 40/42A61K 40/24A61K 40/22A61K 40/17A61K 2239/50A61K 2239/38A61K 2239/57A61K 38/217A61K 47/6813C12N 5/0645A61P 35/00A61K 38/204A61K 38/2006A61K 31/739A61K 2039/505A61K 38/191A61K 39/395C12N 15/1138A61K 45/06A61K 31/7088C07K 16/2896C07K 16/244C07K 2317/76A61K 35/15
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Claims

Abstract

The present invention relates to compositions and methods variously useful in treating cancer, inhibiting graft rejection, and treating autoimmune disease. The compositions and methods include those in which macrophages are conditioned to down regulate or upregulate the expression or activity of SIRPα or its interaction with CD47.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A pharmaceutical composition comprising a one or more agents that suppress the expression or activity of signal regulatory protein α (SIRPα) and one or more agents that activate Protein kinase C (PKC)-Spleen tyrosine kinase (Syk) pathway. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the one or more agents that suppress the expression or activity of SIRPα comprise a nucleic acid that suppresses the expression of SIRPα. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the nucleic acid mediates RNAi, is an antisense oligonucleotide, or is a microRNA. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the nucleic acid is a targeting sequence used in conjunction with gene editing. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the one or more agents that suppress the expression or activity of SIRPα comprise an antibody that suppresses the activity of SIRPα. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the antibody that suppresses the activity of SIRPα is an anti-SIRPα monoclonal antibody. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the one or more agents that suppress the expression or activity of SIRPα comprise a Toll-like receptor (TLR) ligand. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the TLR ligand comprises a CpG oligonucleotide or a polyinosinic:polycytidylic acid (poly I:C). 
     
     
         9 . The pharmaceutical composition of  claim 7 , wherein the TLR ligand comprises GARDIQUIMOD or IMIQUIMOD. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the one or more agents that suppress the expression or activity of SIRPα comprise a Toll-like receptor (TLR) ligand, IFNγ, and IL-6. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the one or more agents that activate the PKC-Syk pathway is phorbol 12-myristate 13-acetate (PMA). 
     
     
         12 . The pharmaceutical composition of  claim 1 , comprising a Toll-like receptor (TLR) ligand, IFNγ, IL-6, and phorbol 12-myristate 13-acetate (PMA). 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the TLR ligand comprises a CpG oligonucleotide or a polyinosinic:polycytidylic acid (poly I:C). 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein the TLR ligand comprises GARDIQUIMOD or IMIQUIMOD.

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