Table 1 Current status of agents targeting negative checkpoint receptors (NCRs)
Drug Target, (Synonym) | Effect on T-cells and immune system | Compound (Synonym) | Drug company (Trade name) | Drug type (application) | Status | Indication |
|---|---|---|---|---|---|---|
CD152 (CTLA4) | Blocking of CTLA4, activation of T-cells and anti-tumor immune response | Ipilimumab (MDX-010) | BMS (Yervoy) | Human MAb, IgG1ĸ (i.v., Q3W) | FDA 25.03.2011 EMA 25.07.2011 Investigational | MEL (metastatic and adjuvant) MEL NSCLC, SCLC |
Tremelimumab (CP-675,206) | AstraZeneca | Human MAb, IgG2ĸ (i.v., Q4-12 W) | Phase II | Mesothelioma, MEL | ||
CD223 (LAG3) | Blocking of LAG3-mediated immune down-regulation; Activation and expansion of tumor antigen-specific T-effector cells; activation of antigen presenting cells to remove tumor debris; | BMS-986016 | BMS | MAb, (i.v.) | Phase I | Relapsed hematologic malignancies |
LAG-525 | Novartis | Humanized MAb, (i.v.) | Phase I | Advanced solid tumors | ||
IMP-701 | Novartis | MAb, (i.v.) | Preclinical | No data available; Cancer | ||
IMP-321 | Prima BioMed | Recombinant human soluble LAG3 MAb fragment (fusion protein), (i.v.) | Phase I/II | Pancreatic cancer, MEL, MRCC, metastatic breast cancer | ||
CD223 (LAG3) | Blocks LAG3; Depletion of activated autoaggressive T-cells | GSK-2831781 (initially IMP-731) | GSK | Humanized MAb, (i.v.) | Phase I | Psoriasis, autoimmune diseases |
CD272 (BTLA) | - | - | - | - | Preclinical | In vitro, murine models |
CD279 (PD1) | Blocking of PD1; Activation of anti-tumor immune response via prevention of CD8+ T-cell exhaustion | Nivolumab (BMS-936558) (MDX-1106) | BMS (Opdivo) | Human MAb, IgG4ĸ (i.v.) | FDA 22.12.2014 EMA 16.07.2015 | MEL, NSCLC, RCC, M. Hodgkin MEL, NSCLC, RCC |
Pembrolizumab (Lambrolizumab) (MK-3475) | Merck (Keytruda) | Humanized MAb, IgG4ĸ (i.v., Q3W) | FDA 04.09.2015 EMA 30.07.2015 | MEL, NSCLC MEL | ||
BGB-A317 | BeiGene | Humanized MAb, (i.v. Q2-3 W) | Phase I | Advanced solid tumors, B-cell malignancies | ||
TSR-042 | Tesaro, AnaptysBio | Humanized MAb, (i.v.) | Phase I | Advanced or metastatic solid tumors | ||
PDR-001 | Novartis | Humanized MAb IgG4ĸ, (i.v.) | Phase I/II | Advanced malignancies, rec./metastatic nasopharyngeal carcinoma | ||
Pidilizumab (CT-011) (MDV9300) | Medivation | Humanized MAb IgG1ĸ, (i.v.) | Phase II | DLBCL, relapsed myeloma, follicular lymphoma | ||
AMP-224 (AFC-111CL) | Creative Biolabs | ADCC enhanced MAb. (i.v.) | Phase I | Advanced, refractory cancer, metastatic CRC | ||
MEDI-0680 (AMP-514) | MedImmune | Humanized MAb IgG4ĸ, (i.v.) | Phase I | Advanced solid tumors | ||
CD366 (TIM3) | Blocking of TIM3; Activation of anti-tumor immune response via prevention of CD8+ T-cell exhaustion | TSR-022 | Tesaro, AnaptysBio | Humanized MAb IgG4, (i.v.) | Phase I | Advanced solid tumors |
MBG-453 | Novartis | MAb, (i.v.) | Phase I | Advanced malignancies | ||
VISTA CD274 (PDL1) | Blocking of VISTA and PDL1; Activation of T-cell proliferation & cytokine production | CA-170 (AUPM-170) | Curis, Aurigene | Small molecule antagonist (p.o.) | Phase I | Advanced solid tumors or lymphomas, nonresponsive to available therapies |
TIGIT | - | - | - | - | Preclinical | Murine cancer models |