Compositions and methods for altering macrophage phenotype
AssigneeNavidea Biopharmaceuticals, Inc.
InventorDavid A. Ralph
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Abstract
Disclosed are methods and compositions for repolarizing a tumor associated macrophage (TAM) from M2 to M1 comprising administering to a subject in need thereof an effective dose of a compound comprising a dextran backbone and one or more CD206 targeting moieties conjugated thereto. In certain aspects, the compound further comprises a therapeutic agent selected from: paclitaxel, gemcitabine, lapatinib, and doxorubicin. In further aspect, the therapeutic agent comprises a chelator and at least one metal ion. In certain implementations, the at least one metal ion comprises at least one Cu(II) ions.
Claims9
A method for repolarizing a tumor associated macrophage (TAM) from an immunosuppressive (M2-like) phenotype to a proinflammatory (M1-like) phenotype comprising administering to a subject in need thereof an effective dose of a compound, wherein the compound is Formula (I);
- wherein
- each X is independently H, L1-A, or L2-R;
- each L1 and L2 are independently an amino-terminated leash;
- each A independently is H or a therapeutic agent bound to the amine-terminated leash, wherein the amino-terminated leash has the formula —(CH2)pS(CH2)q—NH—with an optional attachment with amide, amidine, and/or hydrazone group, wherein p and q are integers from 0 to 5, wherein the therapeutic agent is selected from the group consisting of paclitaxel, gemcitabine, lapitinib, doxorubicin, and a bisphophonate;
- each R indepedently is mannose, fucose, n-acetylglucosamine, or H;
- and n is an integer greater than zero,
- wherein at least one A is the therapeutic agent, and at least one R is mannose.
Dependencies are inferred from the claim text.