Granted Patent
B2
US 12,576,131 · App. 16/963,119 · Granted Mar 17, 2026
Altering inflammatory states of immune cells in vivo by modulating cellular activation states
Assignee:
Fred Hutchinson Cancer Center
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Abstract
Systems and methods to modulate the activation state of immune cells in vivo are described. The systems and methods can be used to transform immunosuppressive macrophages that support cancer growth and metastasis into highly activated tumoricidal macrophages.
Claims (14)
1 . A therapeutic composition comprising nanoparticles comprising mRNA encoding interferon regulatory factor 5 (IRF5) and mRNA encoding IKKβ.
2 . The therapeutic composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
3 . The therapeutic composition of claim 1 , wherein the nanoparticles further comprise mRNA encoding an anticancer gene comprising p53, RB, BRCA1, E1A, bcl-2, MDR-1, p21, p16, bax, bcl-xs, E2F, IGF-I VEGF, angiostatin, oncostatin, endostatin, GM-CSF, IL-12, IL-2, IL-4, IL-7, IFN-γ, TNFα, HSV-tk, or a combination thereof.
4 . The therapeutic composition of claim 1 , wherein the nanoparticles further comprise mRNA encoding glucocorticoid-induced leucine zipper (GILZ).
5 . The therapeutic composition of claim 1 , wherein the nanoparticles further comprise a targeting ligand linked to a surface of the nanoparticles.
6 . The therapeutic composition of claim 5 , wherein the targeting ligand binds CD206, CD163, CD23, CD38, G-protein coupled receptor 18 (Gpr18), formyl peptide receptor 2 (Fpr2), CD64, or CD68.
7 . The therapeutic composition of claim 5 , wherein the targeting ligand comprises di-mannose.
8 . The therapeutic composition of claim 1 , wherein the nanoparticles comprise a positively-charged poly(β)-amino ester core, a star-shaped polymer, a polyglutamic acid coating, a hyaluronic acid coating, a liposome, or a combination thereof.
9 . The therapeutic composition of claim 1 , wherein the nanoparticles comprise a mean diameter of <130 nm.
10 . The therapeutic composition of claim 1 , wherein the nanoparticles comprise a ratio of the mRNA encoding IRF5 to the mRNA encoding Iκκβ of 0.5:1, 1:1, 2:1, 3:1, 4:1, or 5:1.
11 . The therapeutic composition of claim 1 , wherein the nanoparticles comprise a ratio of the mRNA encoding IRF5 to the mRNA encoding Iκκβ of 3:1.
12 . The therapeutic composition of claim 5 , wherein the targeting ligand binds selectively to an immune cell.
13 . The therapeutic composition of claim 12 , wherein the immune cell is a tumor-associated macrophage.
14 . The therapeutic composition of claim 5 , wherein the targeting ligand is an antibody or an antigen-binding fragment thereof.
Assignments (2)
MERGER AND CHANGE OF NAME
Recorded Jun 23, 2022
From: FRED HUTCHINSON CANCER RESEARCH CENTER; SEATTLE CANCER CARE ALLIANCE
To: FRED HUTCHINSON CANCER CENTER
Reel/Frame 060438/0369 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 24, 2020
From: STEPHAN, MATTHIAS
To: FRED HUTCHINSON CANCER RESEARCH CENTER
Reel/Frame 053302/0925 →
Continuity (2)
Provisional Application
62618908
· Jan 18, 2018
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