Table 3.
Summary of strategies targeting TAMs which are currently under investigation in breast cancer preclinical and clinical studies.
| Mechanism of Action | Target | Drug | Partners | Trials |
|---|---|---|---|---|
| TAM killing | Membrane cell receptor activation | Trabectidine | CT, PARP inhibitor |
NCT00050427 NCT00580112 NCT03127215 |
| CSF1-CSF1R inhibition | Emactuzumab Pexidartinib Lacnotuzumab Cabiralizumab |
CT, immune checkpoint inhibitors |
NCT02323191 NCT02760797 NCT01494688 NCT01596751 NCT01525602 NCT01042379 NCT02435680 NCT02807844 NCT03285607 NCT04331067 |
|
| Inhibition of TAM recruitment | CCL2-CCR2 inhibition | Carlutumab | CT | NCT01204996 |
| Modulation of TAM polarization (from M2 into M1 TAM phenotype) | Macrophage | Zoledronic Acid | NA | Approved in both early and metastatic settings |
| CD40 stimulation | Selicrelumab | Other anti-TAM agents |
NCT02225002 NCT02157831 NCT02665416 NCT02760797 |
|
| CR3 stimulation | 1,3–1,6 β-glucan | Immunotherapy | NCT02981303 | |
| Induction of cancer cell phagocytosis by TAMs | CD47-SIRPα inhibition | TTI-621, ALX148 Hu5F9-G4 |
Immunotherapy, anti-VEGF agents, anti-HER2 agents |
NCT02890368 NCT03013218 NCT02216409 NCT02953782 |
| Regulation of antigen presentation by TAMs | TLR7 stimulation | Imiquimod 852A |
CT, RT | NCT00899574, NCT01421017, NCT00821964, NCT00319748 |
| Vaccination | NA | SV-BR-1-GM H2NVAC |
Immunotherapy | NCT04418219, NCT04144023 |
Abbreviations: TAMs, tumor-associated macrophages; CT, chemotherapy; PARP, poly-ADP polymerase; M2pep, M2peptide; CSF1 (R), colony stimulating factor 1 (receptor); CCL2, chemokine C-C motif ligand 2; CCR2, CCL2 receptor; mAb, monoclonal antibody; Fbln7, fibulin 7; CXCL1, C-X-C Motif Chemokine Ligand 1 Pathway; ZnPPIX, zinc protoporphyrin 9; SIRPα, signal regulatory protein alpha; TLR7, toll-like receptor 7; GM-CSF, granulocyte-macrophage colony stimulating factor.