Targeted lnp compositions for in vivo immune cell engineering and methods of use thereof
AssigneeCREATE Medicines, Inc.
InventorsDaniel GETTS, Yuxiao WANG
Life of this patent
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Abstract
The present disclosure provides compositions and methods for making and using engineered phagocytic cells that express a chimeric antigen receptor having an enhanced phagocytic activity for immunotherapy in cancer or infection.
Claims25
1-26. (canceled)
A method of treating a disease or condition in a subject in need thereof comprising administering to the subject a pharmaceutical composition formulated for systemic injection into the subject, the pharmaceutical composition comprising a lipid nanoparticle (LNP) comprising a recombinant RNA molecule, wherein the LNP
- (a) is modified to comprise a surface modification, the surface modification comprising a binding moiety attached to the LNP, wherein the binding moiety comprises an antibody or antigen binding fragment thereof that targets a cell surface receptor;
- (b) comprises cholesterol, a polar lipid, a nonpolar lipid, and a polymeric ethylene glycol (PEG) moiety;
- (c) is from 60-300 nm in diameter;
- and wherein the recombinant RNA molecule
- (i) is encapsulated within the LNP;
- (ii) comprises a sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain comprising an antigen binding domain, a transmembrane domain and an intracellular domain comprising a signaling domain;
- and
- (iii) comprises 5′ and 3′ untranslated regions flanking the sequence encoding the CAR.
The method of claim 49, wherein the mRNA molecule does not comprise pseudouridine.
The method of claim 49, wherein the mRNA molecule comprises a circRNA.
The method of claim 49, wherein the mRNA molecule comprises an unmodified mRNA molecule.
The method of claim 49, wherein the mRNA molecule lacks unnatural bases.
The method of claim 49, wherein the mRNA molecule is an in vitro transcribed mRNA molecule.
A pharmaceutical composition comprising a lipid nanoparticle (LNP) comprising a recombinant RNA molecule, wherein the LNP
- (a) is modified to comprise a surface modification, the surface modification comprising a binding moiety attached to the LNP, wherein the binding moiety comprises an antibody or antigen binding fragment thereof that targets a cell surface receptor;
- (b) comprises cholesterol, a polar lipid, a nonpolar lipid, and a polymeric ethylene glycol (PEG) moiety;
- (c) is from 60-300 nm in diameter;
- and wherein the recombinant RNA molecule
- (i) is encapsulated within the LNP;
- (ii) comprises a sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain comprising an antigen binding domain, a transmembrane domain and an intracellular domain comprising a signaling domain;
- and
- (iii) comprises 5′ and 3′ untranslated regions flanking the sequence encoding the CAR.
Dependencies are inferred from the claim text.