Table 3 Synergistic effect via combination of immunotherapy and HIF inhibitor
Target | Immunotherapy agent | HIF inhibitor agent | Mechanism of HIF inhibitor | Cell | Cell line | Reference |
|---|---|---|---|---|---|---|
PD-1 | PD-1 Ab (clone RMP1–14, rat IgG2a) | PMN-MDSC inhibitor: POG
| Inhibits HIF-1α expression | Melanoma | Mouse: B16F10 | PubChem CID: 14034912 URL: https://pubchem.ncbi.nlm.nih.gov/compound/14034912 [105] |
Breast cancer | Mouse: 4T1 | |||||
PD-1 Ab | IDF-11774
| Inhibits HIF-1α expression | Prostate cancer | Mouse: RM-1 | Pubchem CID: 71542096 URL: https://pubchem.ncbi.nlm.nih.gov/compound/71542096 [106] | |
PD-L1 | PD‐L1 Ab (SP142) | HIF-2α antagonist: PT2385
PT2399
| Both interfere the heterodimerization of HIF-2α with HIF-β | ccRCC | Mouse: XP164, XP373, XP453, XP454 | PubChem CID: 91754484 URL: https://pubchem.ncbi.nlm.nih.gov/compound/91754484 PubChem CID: 91663289 URL: |
CTLA-4 | CTLA4 mAb (UC10-4F10; hamster IgG) | anti-RANKL mAb: denosumab | Downregulates HIF-1α protein expression | Melanoma | Mouse: B16F10, LWT1 | [109] [110] |
Colon carcinoma | Mouse: CT26 | |||||
Prostate carcinoma | Mouse:RM-1 | |||||
Prostate adenocarcinoma | Mouse: Tramp-C1 | |||||
Fibrosarcoma | Mouse: MCA1956 | |||||
PD-1, CTLA-4 | PD-1 (clone RMP1-14) CTLA-4 mAb (clone 9D9) | ENTPD2 inhibitor: ARL67156
POM-1
| Inhibit downstream product MDSC to upregulate HIF-1α | HCC | Human: MHCC97L PLC/PRF/5, Hep3B Mouse: Hepa1-6 | PubChem CID: 146157453 URL: https://pubchem.ncbi.nlm.nih.gov/compound/146157453 PubChem CID: 71311259 URL: https://pubchem.ncbi.nlm.nih.gov/compound/71311259 [111] |
PD-1, CTLA4 | CTLA-4 Ab (9H10) PD-1 Ab (clone: 29 F.1A12, 135204) | Ganetespib
| Inhibits Hsp90 and leads to HIF-1α degradation | Colon carcinoma | Mouse: MC38/gp 100 | PubChem CID: 135564985 URL: https://pubchem.ncbi.nlm.nih.gov/compound/135564985 [114] |
Melanoma | Human: melanoma 2338, 2400, 2549, 2559, 2812 | |||||
PD-L1, PD-1, CTLA-4 | Anti-PD-1 (clone RMP1-14) | CXCR4 antagonist: X4-136 | Inhibits CXCR-4 to positively feedback HIF-1α | Melanoma | Mouse: B16-OVA | [115] [116] |
Anti-PD-L1 (clone: 10F.9G2) | Renal Cancer | Mouse: Renal Cancer Renca DM (Renca-2159-84H) | ||||
Anti-CTLA-4 Ab (clone: 9D9) | ||||||
IL-1 | miR-144-3p mimic | COX2 inhibitor: celecoxib
| Inhibits IL-1β/NF-κB/COX-2/ HIF-1α pathways | NSCLC | Human: A549 | PubChem CID: 349,978,031 URL: https://pubchem.ncbi.nlm.nih.gov/substance/349978031 [117] |
