Table 2. Clinical trials of potential drugs for TAM targeting.
| Strategy | Target | Drug | Drug type | Tumor type | Clinical trial number | Ref. |
|---|---|---|---|---|---|---|
| TAM recruitment and survival | CCL2-CCR2 axis | CNTO 888 (Carlumab) | CCL2 inhibitor (mAb) | Solid tumors Prostate cancer |
NCT00537368 NCT00992186 |
(193,194) |
| Trabectedin | CCL2 inhibitor (small molecule) | Ovarian cancer Liposarcoma Leiomyosarcoma |
NCT02163720 NCT01343277 |
(195,196) | ||
| PF-04136309 | CCR2 inhibitor (small molecule) | Pancreatic ductal adenocarcinoma |
NCT02732938 NCT01413022 |
(197,198) | ||
| MLN1202 | CCR2 inhibitor (mAb) | Bone metastasis | NCT01015560 | (199) | ||
| CSF1-CSF1R axis | LY3022855 | CSF1R inhibitor (mAb) | Solid tumors Breast or prostate cancer |
NCT01346358 NCT02265536 |
(200,201) | |
| AMG 820 | CSF1R inhibitor (mAb) | Solid tumors |
NCT01444404 NCT02713529 |
(202,203) | ||
| PLX3397 (Pexidartinib) | CSF1R inhibitor (small molecule) | Solid tumors Glioblastoma Multiforme Pancreatic ductal adenocarcinoma and colorectal cancer |
NCT02452424 NCT01349036 NCT02777710 |
(204-206) | ||
| RO5509554/RG7155 (Emactuzumab) | CSF1R inhibitor (mAb) | Solid tumors | NCT01494688 | (207) | ||
| Cabiralizumab | CSF1R inhibitor (mAb) | Solid tumors Pancreatic ductal adenocarcinoma |
NCT03158272 NCT03599362 |
(208,209) | ||
| BLZ945 | CSF1R inhibitor (small molecule) | Solid tumors | NCT02829723 | (210) | ||
| CXCL12-CXCR4 axis | LY2510924 | CXCR4 inhibitor (small molecule) | Solid tumors | NCT02737072 | (211) | |
| X4P-001 (Mavorixafor) | CXCR4 inhibitor (small molecule) | Melanoma | NCT02823405 | (212) | ||
| TAM activation | CD40 | ChiLob 7/4 | CD40 agonist (mAb) | Non-Hodgkin lymphoma and solid tumors | NCT01561911 | (213) |
| CP-870,893 | CD40 agonist (mAb) | Solid tumors Melanoma |
NCT00607048 NCT01103635 |
(214,215) | ||
| GM.CD40L | GM-CSF/CD40 Ligand (vaccine) | Lung adenocarcinoma | NCT01433172 | (216) | ||
| APX005M | CD40 agonist (mAb) | Melanoma and NSCLC | NCT03123783 | (217) | ||
| TLR7 | Imiquimod | TLR7 agonist (small molecule) | Breast cancer Basal cell carcinoma |
NCT01421017 NCT00899574 NCT00803907 |
(218,219) | |
| TLR7, 8, and 9 | IMO-8400 | TLR7,8, and 9 inhibitor (anti-sense oligonucleotide) | Diffuse large B cell lymphoma | NCT02252146 | (220) | |
| TLR7/8 | Resiquimod | TLR 7/8 agonist (small molecule) | Melanoma Cutaneous T cell lymphoma |
NCT00821652 NCT01676831 |
(221,222) | |
| NKTR-262 | TLR 7/8 agonist (small molecule) | solid tumors | NCT03435640 | (223) | ||
| TLR8 | Motolimod (VTX-2337) | TLR8 agonist (small molecule) | Ovarian cancer ovarian, fallopian tube or primary peritoneal cancer Squamous cell carcinoma of the head and neck |
NCT02431559 NCT01666444 NCT01334177 |
(123,224,225) | |
| TLR9 | EMD 1201081 | TLR9 agonist (small molecule) | Squamous Cell Carcinoma of the Head and Neck Cancer | NCT01040832 | (124) | |
| IMO-2055 | TLR9 agonist (small molecule) | Colorectal Cancer NSCLC |
NCT00719199 NCT00633529 |
(125,226) | ||
| SD-101 | TLR9 agonist (synthetic CpG oligonucleotide) | Low-grade B-cell lymphoma Melanoma |
NCT02254772 NCT02521870 |
(227,228) | ||
| IL6-IL6R axis | Tocilizumab | IL6R inhibitor (mAb) | Ovarian cancer | NCT01637532 | (88) | |
| Siltuximab | IL6 inhibitor (mAb) | Smoldering multiple myeloma | NCT01484275 | (89) | ||
| SIRP-α/CD47 axis | TTI-622 | SIRP-α inhibitor (Fc-fusion protein) | Non-Hodgkin lymphoma | NCT03530683 | (229) |
CCL C-C, motif chemokine ligand; CCR C-C, chemokine receptor; CD, cluster of differentiation; CSF, colony stimulating factor; CXCR, C-X-C chemokine receptor; GM, granulocyte-macrophage; IL Interleukin; mAb, monoclonal antibody; NSCLC, non-small cell lung carcinoma; TLR, toll-like receptor; SIRP, signal regulatory protein.