Table 3.

Schematic diagram of progressive clinical trials on OS TAM-centered treatments.

Clinical trial	Phase	Combined drug	Interventions	Therapeutic target
NCT02441309	II	Ifosfamide + Mifamurtide	Group 1: mifamurtide alone; Group 2: ifosfamide alone for 6 weeks then ifosfamide + Mifamurtide for 6 weeks, then mifamurtide alone for 30 weeks; Group 3: ifosfamide + mifamurtide for 12 weeks then mifamurtide alone for 24 weeks. All participants will receive 36 weeks or more of mifamurtide.	Macrophage
NCT00631631	—	—	Mifamurtide (L-MTP-PE), intravenous, at a dose of 2 mg/m^2 twice weekly (at least 3 days apart) for 12 weeks, and then weekly for an additional 24 weeks, for a total of 48 doses in 36 weeks.	Macrophage
NCT03811886	I	Natalizumab	Traditional 3 + 3 escalation of natalizumab at a weight-based dosing 2 mg/kg not exceeding 300 mg. If no subjects experience a dose limiting toxicity (DLT), 3 more subjects are enrolled at the next dose of 3 mg/kg, not to exceed 300 mg. If no subjects experience a DLT, 3 more subjects will be enrolled at the next and final dose of 4 mg/kg, not exceeding 300mg.	TAMs
NCT01459484	II	Methotrexate, Cisplatinum, Doxorubicine, Ifosfamide + Mifamurtide	Group1: Chemotherapy for patients who over express ABCB1/P-glycoprotein:PRE-SUGERY TREATMENT: methotrexate:12 g/m2 (3cycles) + cisplatinum:120 mg/m2 (3 cycles), doxorubicin + ADM 75 mg/m2 (3 cycles); POST-SURGERY TREATMENT for good responder patients with positive PGLYCOPROTEIN:methotrexate 12 g/m2 (10 Cycles) cisplatinum 120 mg/m2; Doxorubicin 90 mg/m2 MEPACT 2 mg/m2 twice a week for the first 3 months the weekly for the next 6 months (total length of treatment: 44 weeks); POST-SURGERY TREATMENT for poor responder patients with positive P-GLYCOPROTEIN: methotrexate 12 g/m2; cisplatinum 120 mg/m2; doxorubicin 90 mg/m2, ifosfamide 15 g/m2 MEPACT 2 mg/m2 twice a week for the first 3 months the weekly for the next 6 months (total length of treatment 44 weeks);Group 2: high-grade osteosarcoma treatment for patients who do not over express ABCB1/P-glycoprotein: high-grade osteosarcoma that does not over express ABCB1/P-glycoprotein will be treated with a standard 3-drug regimen PRE-SUGERY TREATMENT: methotrexate: 12 g/m2 (3 cycles), cisplatinum: 120 mg/m2 (3 cycles) doxorubicin: ADM 75 mg/m2 (3 cycles) POST-SURGERY TREATMENT: methotrexate 12 g/m2 (10 cycles), cisplatinum 120 mg/m2; doxorubicin 90 mg/m2 (total length 34 weeks)	TAMs
NCT02584647	I	Sirolimus + PLX3397	Subjects with unresectable or metastatic sarcoma will take orally PLX3397 (600 - 1000mg) in combination with Sirolimus (2-6 mg) daily	TAMs
NCT02502786	II	GM-CSF + humanized anti-GD2 antibody: hu3F8	One cycle consists of treatment with hu3F8 at a dose of 2.4 mg/kg/dose for 3 days (day 1, 3, and 5) in the presence of subcutaneous (sc) GM-CSF (day 4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. Cycles are repeated at ~2–4-week intervals between first days of hu3F8, through 5 cycles.	GM-CSF