Table 3 Ongoing clinical trials targeting TAMCs
From: Tumor-associated myeloid cells in cancer immunotherapy
Strategies | Class | Treatment | Conditions | With ICBs or not | Outcomes | Adverse effects |
|---|---|---|---|---|---|---|
Blocking expansion and recruitment of TAMCs | CCR2 inhibitor | PF-04136309, MLN1202, BMS-813160, etc | Pancreatic ductal adenocarcinoma, melanoma, metastatic cancer, etc | Both monotherapy and synergistic ICBs are available | ORR was 16.7–49%. About 33% of patients had reduced metastasis markers. But some trials have been stopped for lack of clinical benefit | Fatigue and anemia were common. DLTs were present. Neutropenia may occur with concurrent chemotherapy |
VEGFR inhibitor | Axitinib, Cabozantinib, Pazopanib, etc | Renal cell carcinoma, breast cancer, small cell lung cancer, etc | Both monotherapy and synergistic ICBs are available | OS and PFS were significantly prolonged, and ORR was increased | The incidence rate of serious AEs was about 40%. The most common AE was diarrhea | |
CSF1R inhibitor | Cabiralizumab, PLX3397, ARRY-382, etc | Advanced solid tumor, melanoma, non-small cell lung cancer, etc | Mostly in collaboration with ICBs | The objective response rate was 0–16.7%. PFS did not prolong significantly | The incidence rate of serious AEs and DLTs was 0–54.5%. Gastrointestinal diseases were common | |
Mitigating the immunosuppressive ability of TAMCs | COX-2 inhibitor | Celecoxib, apricoxib, etc | Breast cancer, non-small cell lung cancer, etc | Collaboration with ICBs is rare | PFS did not significantly prolong or even shorten. There was no clinical benefit | The incidence rate of serious AEs was similar to that of placebo group |
PDE5 inhibitor | Tadalafil, Sildenafil, etc | Head and neck squamous cell carcinoma, prostatic neoplasms, etc | No | The activity of Arg-1 and iNOS was significantly decreased, reversing tumor specific immune suppression | No AEs are reported | |
TLR agonist | CMP-001, Imiquimod, SD-101, etc | Melanoma, head and neck cancer, breast cancer, etc | Mostly in collaboration with ICBs | ORR was 0–55.6%, and progressive disease accounted for 11.1–44.4%. MPR also showed a mix of good and bad outcomes | The incidence rate of serious AEs was 16.67–44.4%. Chills and fatigue were prominent | |
Direct depletion | VEGFR inhibitor | Sunitinib malate, ZD6474, Apatinib, etc | Renal cell carcinoma, bladder cancer, breast cancer, gastric cancer, etc | Both monotherapy and synergistic ICBs are available | PFS and OS were prolonged in most trials. Some studies have shown that MDSC mediated immunosuppression is reversed | The incidence rate of serious AEs was 6.67–40%. Leukocytes and platelets were often affected |
C-kit inhibitor | Imatinib, Masitinib, Dasatinib, Dovitinib, etc | Salivary gland neoplasm, non-small cell lung cancer, melanoma, thyroid cancer, etc | Collaboration with ICBs is rare | Clinical benefit was limited. PFS was prolonged in some trials, but the results of some trials were mainly progressive disease | The incidence rate of serious AEs was 2.44–65%. Among them, diarrhea, nausea and vomiting were easy to occur | |
Chemo therapy | Cisplatin, 5-FU, Carboplatin, Paclitaxel, Doxorubicin, etc | Esophageal neoplasms, breast cancer, non-small cell lung cancer, ovarian cancer, sarcoma, etc | Both monotherapy and synergistic ICBs are available | Effectiveness varies greatly depending on tumor type, drug dose, combination therapy, etc. Both trials with significant clinical benefit and trials with low ORR exist | Nausea, constipation and diarrhea were prominent in AEs. The hematopoietic system such as neutrophils and platelets were susceptible |