Enhanced macrophages
AssigneeResolution Therapeutics Limited
InventorsLara CAMPANA, Kayleigh THIRLWELL, Niya ALEKSANDROVA ALEKSIEVA
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Abstract
The present invention relates to a macrophage engineered to express a Matrix Metallopeptidase and therapeutic uses thereof. Such a macrophage may be for use in treatment of an inflammatory condition comprising a fibrotic element in a subject such as inflammatory organ damage. The inflammatory condition may be acute or chronic and may involve a fibrotic element.
Claims38
An engineered macrophage for use in treating an inflammatory condition with a fibrotic element, wherein the macrophage is engineered with exogenous nucleic acid encoding MMP9.
An engineered macrophage as claimed in any preceding claim, wherein said macrophage overexpresses the said coding sequence encoding MMP9.
An engineered macrophage as claimed in any preceding claim, wherein said exogenous nucleic acid comprises a DNA molecule, an RNA molecule, or a non-viral vector.
An engineered macrophage as claimed in any preceding claim, wherein said exogenous nucleic acid is transfected into the macrophage, preferably via electroporation.
An engineered macrophage as claimed in any preceding claim wherein said macrophage has a repressed STING pathway or is treated with anti-inflammatory agents.
An engineered macrophage according to any preceding claim, wherein said macrophage exhibits a pro-restorative phenotype.
An engineered macrophage according to any preceding claim, wherein said macrophage is autologous or allogenic to the subject, optionally wherein the macrophage is derived from a human monocyte, or a stem cell, further optionally wherein the stem cell is an induced pluripotent stem cell.
An engineered macrophage according to any preceding claim, wherein said inflammatory condition is chronic.
An engineered macrophages according to any preceding claim, wherein the engineered macrophage secretes MMP9 and the secreted MMP9 protein level is greater than 200 ng/ml when the macrophage is cultured in vitro at a cell concentration of 4×106/ml.
A population of engineered macrophages comprising engineered macrophages for use according to any preceding claim.
A composition comprising an engineered macrophage or population of engineered macrophages for use according to any preceding claim.
A method of improving the resolution of fibrosis in a chronic condition, comprising the use of an engineered macrophage, population of engineered macrophages or a composition according to any of the preceding claims.
A method of treating an inflammatory condition with a fibrotic element, comprising the use of a macrophage engineered with an exogenous sequence encoding for MMP9.
An engineered macrophage, wherein the macrophage is engineered to express MMP9.
Dependencies are inferred from the claim text.