The present invention relate to autologous isolated unpolarized human macrophages for use in the treatment of liver disease and macrophages for use in a method of treating fibrosis in a human in need thereof.

Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade.

Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade.

A method of treating an inflammatory disorder in a subject, comprising administering to a subject in need thereof a nucleic acid molecule for inhibiting the expression of Hom-1.

A method of treating an inflammatory disorder in a subject, comprising administering to a subject in need thereof a nucleic acid molecule for inhibiting the expression of Hom-1.

The present invention belongs to the technical fields of immunology and oncologic therapies. Provided are a tumor microenvironment-regulated CAR-monocyte/macrophage, and a preparation method therefor and the use thereof. When the CAR-monocyte/macrophage forms a chimeric antigen receptor composite structure, GM-CSF can be expressed intracellularly and autocrine to extracellular to promote the differentiation of the CAR-monocyte/macrophage to form an M1 type macrophage, so that the tumor microenvironment can be further regulated while the property of resisting M2 type macrophage reversal in the tumor microenvironment is maintained, thereby sensitizing the anti-tumor effect of the CAR-monocyte/macrophage. On the basis of GM-CSF, a tumor microenvironment-regulated CAR macrophage technology platform is constructed, which can maintain the M1-type characteristics of CAR-M and can also produce a TME reversal effect, thereby achieving the efficient anti-tumor effect of a CAR-monocyte/macrophage.

The present invention belongs to the technical fields of immunology and oncologic therapies. Provided are a tumor microenvironment-regulated CAR-monocyte/macrophage, and a preparation method therefor and the use thereof. When the CAR-monocyte/macrophage forms a chimeric antigen receptor composite structure, GM-CSF can be expressed intracellularly and autocrine to extracellular to promote the differentiation of the CAR-monocyte/macrophage to form an M1 type macrophage, so that the tumor microenvironment can be further regulated while the property of resisting M2 type macrophage reversal in the tumor microenvironment is maintained, thereby sensitizing the anti-tumor effect of the CAR-monocyte/macrophage. On the basis of GM-CSF, a tumor microenvironment-regulated CAR macrophage technology platform is constructed, which can maintain the M1-type characteristics of CAR-M and can also produce a TME reversal effect, thereby achieving the efficient anti-tumor effect of a CAR-monocyte/macrophage.

Described herein are compositions and methods for treating various indications in a subject including, but not limited to, atherosclerosis, cardiovascular diseases, inflammation, chronic inflammatory diseases, wounds, and spinal cord injuries. In some embodiments, the compositions and methods comprise a modified macrophage or monocyte comprising surface-expressed CD47-targeted chimeric antigen receptor (CAR) proteins and lipid-based particles conjugated to a surface of the modified macrophage or monocyte, wherein the lipid-based particles comprise a -cyclodextrin (-CD). In some embodiments, the lipid-based particles comprise lipid nanoparticles (LNPs).

Described herein are compositions and methods for treating various indications in a subject including, but not limited to, atherosclerosis, cardiovascular diseases, inflammation, chronic inflammatory diseases, wounds, and spinal cord injuries. In some embodiments, the compositions and methods comprise a modified macrophage or monocyte comprising surface-expressed CD47-targeted chimeric antigen receptor (CAR) proteins and lipid-based particles conjugated to a surface of the modified macrophage or monocyte, wherein the lipid-based particles comprise a -cyclodextrin (-CD). In some embodiments, the lipid-based particles comprise lipid nanoparticles (LNPs).

The present application provides compositions and methods for producing antigen presenting cells (APCs) from monocytes (e.g., monocytes from cancer patients) that involve an IL-10 receptor activator (e.g., IL-10), IFN receptor activator (e.g., IFN), TNF receptor activator (e.g., TNF), IL-4 receptor activator (e.g., IL-4), GM-CSF receptor activator (e.g., GM-CSF), and/or IL-6 receptor activator (e.g., IL-6). APCs produced accordingly are also provided, as well as methods of activating immune cells (e.g., T cells) via co-culturing with APCs. The activated immune cell compositions and the methods of treatments that involve the activated immune cells are also provided.