Table 2 Current status of therapeutic agents targeting ligands of negative checkpoint receptor (NCR)
Drug Target, (Synonym) | Effect on T-cells and immune system | Compound (Synonym) | Drug company (Trade name) | Drug type (application) | Status | Indication |
|---|---|---|---|---|---|---|
CD270 (HVEM) | Activation/Inhibition | - | - | - | Preclinical | - |
CD274 (PDL1) | Blocks PD1/PDL1 ligation; Activation of anti-tumor immune response via prevention of CD8+ T-cell exhaustion | Durvalumab (MEDI-4736) | AstraZeneca | Human MAb IgG1ĸ (i.v., Q2-3 W) | FDA 17.02.2016 BTD Phase III Phase I/II | Metastatic urothelial cancer NSCLC Head and neck, gastric cancer, pancreatic cancer, hematologic malignancies, myelodysplastic syndromes |
Atezolizumab (MPDL-3280A) (RG7446) | Roche Genentech (Tecentriq) | Humanized MAb IgG1ĸ, (i.v., Q3W) | FDA 18.05.2016 Phase III | Metastatic urothelial cancer NSCLC | ||
Avelumab (MSB-0010718C) | Merck & Pfizer | Human MAb IgG1ĸ, (i.v., Q2W) | Phase III | Advanced malignancies, bladder cancer, ovarian cancer, MRCC, head and neck, NSCLC, gastric cancer, Merkel cell carcinoma, M. Hodgkin | ||
BMS-936559 (MDX-505) | BMS | Human MAb IgG4 ĸ, (i.v., Q2W) | Phase I | MEL, advanced refractory solid tumors and hematologic malignancies | ||
CD274 (PDL1) VISTA | Blocking of PDL1 and VISTA - > indirect activation of T-cell proliferation & cytokine production | CA-170 (AUPM-170) | Curis, Aurigene | Small molecule antagonist (p.o., BID Q4D) | Phase I | Advanced solid tumors or lymphomas, non-responsive to available therapies |
HGMB1 | Sensitizes MDR AML cells to chemotherapy, significant decrease in AML cell proliferation | miR181b | - | Inhibits HMGB1 expression | Preclinical | In vitro |