Table 1.
Published clinical trials of immunotherapy combined with inhibitors of molecules associated with ECM stiffness.
| Target type | Targets | Cancer type | Immuno-therapy type | Key molecules in immunotherapy | Therapy drugs | Efficacy | Phase | NCT number | Number of patients | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|
| Mechano-transduction signal pathway | TGF-β | Head and neck cancer | ICB | PD-L1 | M7824 | PR (35.7%) | I/II | NCT04247282 | 14 | [156] |
| TGF-β | HNSCC | ICB | PD-L1 | M7824 | PR (12.5%), SD (12.5%) | I | NCT02517398 | 32 | [157] | |
| TGF-β | Esophageal adenocarcinoma | ICB | PD-L1 | M7824 | PR (10%), SD (10%) | I | NCT02699515 | 30 | [158] | |
| TGF-β | Esophageal adenocarcinoma | ICB | PD-L1 | M7824 | PR (20%), SD (13.3%) | I | NCT02517398 | 30 | [159] | |
| TGF-β | Biliary tract cancer | ICB | PD-L1 | M7824 | CR (6.7%), PR (13.3%), SD (20%) | I | NCT02699515 | 30 | [162] | |
| TGF-β | HPV-associated malignancies | ICB | PD-L1 | M7824 | CR (8.5%), PR (22%), SD (13.6%) | I/II | NCT02517398, NCT03427411 | 59 | [163] | |
| TGF-β | Colorectal cancer | ICB | PD-L1 | M7824 | PR (3.1%), SD (3.1%) | I | NCT02517398 | 32 | [164] | |
| TGF-β | Solid tumors | ICB | CD73 | GS-1423 | PR (4.8%), SD (33.3%) | I | NCT03954704 | 21 | [165] | |
| TGF-β1, TGF-β2 | Ovarian cancer | TCV | Autologous tumor cell vaccine | Gemogenovatucel-T | N.A. | IIb | NCT02346747 | 47 | [166] | |
| TGF-β2 | Non-small cell lung cancer | TCV | Allogeneic tumor cell vaccine | Belagenpumatucel-L | N.A. | III | NCT00676507 | 270 | [167] | |
| TGF-βRII | Solid tumors | ICB | PD-L1 | SHR-1701 | CR (1.7%), PR (10.7%), SD (19.8%) | I | NCT03710265 | 121 | [168] | |
| TGF-βRII | Prostate cancer | ACT | CAR-T | DnTGF-βRII-T2A-Pbbz CAR T cells | N.A. | I | NCT03089203 | 17 | [169] | |
| TGF-βRII | Prostate cancer | ACT | CAR-T | CART-PSMA-TGFβRDN cells | N.A. | I | NCT03089203 | 14 | [170] | |
| FAK | Pancreatic ductal adenocarcinoma | ICB | PD-L1 | Defactinib, Pembrolizumab, Gemcitabine |
PR (5%) SD (75%) |
I | NCT02546531 | 20 | [171] | |
| CAF | FAP | Solid tumors | ICB | PD-L1 | RO7122290, Atezolizumab |
CR (1.7%) PR (7.8%) |
I | N.A. | 115 | [172] |
| FAP | Pleural mesothelioma | ACT | CAR-T | Anti-FAP-Δ-CD28/CD3ζ CAR T cells | SD (100%) | I | NCT01722149 | 1 | [130] | |
| FGFR4 | Hepatocellular carcinoma | ICB | PD-L1 | BLU-554, CS1001 |
CR (25%) PR (25%) SD (50%) |
Ib/II | NCT04194801 | 4 | [173] | |
| FGFR1–4 | Urothelial carcinoma | ICB | N.A. | Erdafitinib | ORR (59.1%) | II | NCT02365597 | 22 | [174] |
ACT adoptive cell therapy, CAF cancer-associated fibroblasts, CR complete response, FAK focal adhesion kinase, FGFR fibroblast growth factor receptor, ICB immune checkpoint blockade, HNSCC head and neck squamous cell carcinoma, HPV human papillomavirus, N.A. not available, PR partial response, pts patients, SD stable disease, TCV therapeutic cancer vaccine.