Table 5 Strategies of targeted therapy for TAMs
Strategy | Method | Function | References |
|---|---|---|---|
To reduce TAMs generation | Clodronate-containing liposomes (CL) Engeletin, CSF1/CSF1R inhibitors (MCS110, Pexidartinib and Emactuzumab), cox-oxidase inhibitors | CL can deplete macrophages in vivo and inhibitors of chemokines can reduce TAMs recruitment | |
To reactivate M1 TAMs phagocytosis | IFN-γ/IDO1 Anti-CD47 antibodies (Hu5F9-G4, HX009, AK117) HMGB1 inhibitors (A Box, RAP and EP), TGF-β receptor I inhibitors (SB4x), DNMTi 5-Azacytidine (5AZA-C) and ornithine decarboxylase inhibitor α-difluoromethylchlorine (DFMO) TAM receptors inhibitors (BMS-777607, BGB324 and A VB-S6-500) | Targeting IFN-γ/IDO1 pathway, blocking CD47-SIRPα axis and using several valid drugs can reactivate macrophage phagocytosis and convert M2 into M1 macrophages Blocking TAM receptors can inhibit TAM activation and polarization | |
To inhibit macrophage-derived molecules | Broad-spectrum MMP inhibitor (CP-471,474) Selective MMP-12 inhibitors (CGA, CGA-1 and AGA) uPA inhibitor B-428 IL-6 inhibitor Siltuximab, Tocilizumab and Cetuximab TGF-β inhibitor Fresolimumab (GC1008), LY3022859, LY2109761 and 1D11 IL-10 receptor-blocking mAb (αIL-10R; clone 1B1.3A) | Inhibitors of TAMs-derived molecules (MMPs, uPA, IL-6, TGF-β, IL-10) were used to block the occurrence and development of tumor cells | |
CAR macrophage therapy | Edited specific chimeric antigen receptor on macrophages to target antigen (such as CD19, HER2) | CAR-M therapy can reverse M2 into M1 macrophages and activate phagocytosis | |
TAMs-based immune vaccines | Fused macrophage–tumor cytomembrane with vaccine adjuvant (CpG ODNs) Therapeutic vaccine with TAMs receptor inhibitor | TAMs-based immune vaccines can increase M1 macrophages and enhance immune response of immune cells. Combining therapeutic vaccine with TAMs receptor inhibitor obtains synergistic therapeutic effects | |
TAMs nanobiotechnology | Macrolide-Au nanorod aCD47@CaCO3 NPs R848-loaded NPs Supramolecular NPs | Nanobiotechnology can target TAMs to boost anti-tumor effect, release CD47, or active TLR-7/TLR-8 to amplify M1 repolarization and phagocytosis |