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Table 2 Immunotherapeutic strategies that target CAFs in clinical and/or preclinical studies

From: Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy

Drugs Mechanisms Combination therapy Biological effects Cancer models Status Refs
SynCon DNA vaccine FAP deletion Anti-tumor vaccine Overcomes immune tolerance Lung cancer Preclinical [100]
FAP-specific CAR T cell FAP deletion Anti-tumor CAR T cell Enhances anti-tumor immunity Lung cancer Preclinical [116]
Oncolytic adenovirus FAP deletion No Enhances anti-tumor immunity CRC Preclinical [118, 119]
ATAR (vitamin A analog) Vitamin A storage and PSC deactivation Gemcitabine Enhances anti-tumor immunity; inhibits tumor cell growth PDAC Preclinical [126]
Calcipotriol (vitamin D analog) Vitamin D receptor activation and PSC deactivation Anti-PD-1 immunotherapy Reverses tumor immunosuppression PDAC Phase II [10]
AMD3100 Blocks the CXCL12-CXCR4 interaction Anti-PD-L1 immunotherapy Reverses tumor immunosuppression PDAC Preclinical [96]
131I-m81C6 (anti-tenascin mAb) Radioimmunotherapy No Reverses tumor immunosuppression Recurrent malignant glioma Phase II [135]
Ruxolitinib (JAK inhibitor) JAK-STA3 pathway inhibition Capecitabine Inhibits tumor-promoting inflammation Metastatic pancreatic cancer Phase II [129]
IPI-926 Hedgehog pathway inhibition Gemcitabine Reverses tumor immunosuppression PDAC Preclinical [133]
NIS793 ABBV151 Blocking pan-TGF-β and GARP Anti-PD-1 immunotherapy Reverses tumor immunosuppression Breast, lung, HCC, CRC, pancreatic and renal cancer Phase I [62]
  1. FAP fibroblast activation protein, CAR chimeric antigen receptor, ATRA all-trans retinoic acid, CXCL12 CXC-chemokine ligand 12, CXCR4 CXC-chemokine receptor 4, PD-1 programmed cell death-1, PD-L1 programmed cell death 1 ligand, JAK Janus kinase, STAT3 signal transducer and activator of transcription 3, mAb monoclonal antibody, PSC pancreatic stellate cell, TGF-β transforming growth factor-β, GARP glycoprotein A repetitions predominant protein, PDAC pancreatic ductal adenocarcinoma, HCC hepatocellular carcinoma, CRC colorectal cancer