Table 3 Current status of therapeutic agents targeting activating checkpoint receptors
Drug Target (Synonym) | Effect on T-cells and immune system | Compound (Synonym) | Drug company (Trade name) | Drug type (application) | Status | Indication |
|---|---|---|---|---|---|---|
CD27 | Binds and activates CD27 - > activation of anti-tumor immune response; Treg depletion; Direct targeting of CD27 expressing tumors | Varlilumab (CDX-1127) | Celldex | Human mAb IgG1ĸ, (i.v., D1,8,15,22 Q8W) | Phase I/II | CRC, NSCLC, RCC, MEL, ovarian cancer, head and neck squamous cell carcinoma |
CD28 | Immunosuppression via preferential activation of Tregs | TAB-08 (TGN-1412) | TheraMab (TeGenero) | Humanized MAb IgG4ĸ, (i.v., Q1W) | Phase I/II | Rheumatoid arthritis, Psoriasis, SLE |
CD134 (OX40) | Binds and activates OX40 - > increases T-cell proliferation and cytokine secretion - > activation of dormant anti-tumor immune response + reduction and suppression of Tregs | PF-04518600 (PF-8600) | Pfizer | Human MAb IgG2, (i.v.) | Phase I | Neoplasms |
MOXR-0916 | Genentech | Humanized MAb IgG1, (i.v.) | Phase I | Advanced or metastatic tumors | ||
MEDI-0562 | MedImmune | Humanized MAb (i.v.) | Phase I | Advanced or metastatic tumors | ||
MEDI-6469 | MedImmune | Humanized MAb (i.v.) | Phase I | Metastatic CRC, locoregionally advanced head and neck cancer | ||
CD137 (ILA, 4-IBB) | Activation and expansion of T-cells and anti-tumor immune response | Urelumab (BMS-663513) | BMS | Human MAb IgG4ĸ (i.v.) | Phase I | Recurrent glioblastoma, advanced solid tumors, hematologic neoplasms |
Utomilumab (PF-05082566) | Pfizer | Human MAb IgG2ĸ (i.v.) | Phase I | Avanced Solid Tumors | ||
CD270 (HVEM) | Activation/Inhibition | - | - | - | Preclinical | - |
CD278 (ICOS) | Activation | - | - | - | Preclinical | - |
CD357 (GITR) | Binds and activates GITR - > activates tumor tumor antigen specific T-effector cells, suppresses Tregs - > activates anti-tumor immune response | MK-4166 | Merck | MAb, (i.v.) | Phase I | Advanced Solid Tumors |
INCAGN-01876 | Agenus | MAb, (i.v.) | Phase I | Advanced or Metastatic Solid Tumors | ||
TRX-518 | Leap Therapeutics | Humanized MAb, (i.v.) | Phase I | Advanced Solid Tumors, MEL | ||
GWN-323 | Novartis | MAb, (i.v.) | Phase I/II | Advanced solid tumors, lymphomas | ||
TLT-2, TREML | Activation | - | - | - | Preclinical | - |