Introduction
Target | Expression | Mechanism | Drug | Type of drug | Phase | Identifier |
---|---|---|---|---|---|---|
Inhibitory pathways | ||||||
LAG‑3 | Activated T cells, NK cells, B cells, plasmacytoid DCs | Regulates proliferation, activation and homeostasis of T cells | Relatlimab (BMS-986016) | mAb | II | NCT03743766 |
XmAb22841 | Bispecific Ab (anti-CTLA‑4 and anti-LAG-3) | I | NCT03849469 | |||
TIM‑3 | Th17 cells, Tregs and innate immune cells (DCs, NK cells, monocytes), TILs | Mediates CD8+ T cell exhaustion, regulates macrophage activation | Cobolimab (TSR-022) | mAb | II | NCT04139902 |
INCAGN02390 | mAb | I/II | NCT04370704 | |||
RO7121661 | Bispecific Ab (anti-PD‑1 and anti-TIM-3) | I | NCT03708328 | |||
TIGIT | T cells, Tregs, NK cells, TILs | Regulates T cell activity, increases IL-10 secretion | Vibostolimab (MK-7684) | mAb | I/II | NCT04305054 NCT04305041 NCT04303169 |
B7-H3 | APCs, NK cells, tumor and endothelial cells | Inhibits T cell activation, proliferation and cytokine production | Enoblituzumab (MGA271) | mAb | I | NCT02475213 |
BTLA | Majority of lymphocytes | Inhibits T and B cell activation, proliferation and cytokine production | TAB004/JS004 | mAb | I | NCT04137900 |
VISTA | Neutrophils, monocytes, macrophages, DCs, CD4+ and CD8+ T cells, TILs | Regulates TLR signaling in myeloid cells, controls myeloid cell-mediated inflammation and immunosuppression | JNJ-61610588 | mAb | I | NCT02671955 |
CA-170 | Small molecule antagonist of PD‑1 and VISTA | I | NCT02812875 | |||
Stimulatory pathways | ||||||
OX-40 | Activated T cells, APCs | Promotes T effector proliferation, inhibits Treg function | PF-04518600 | mAb | II | NCT02554812 |
GITR | Tregs (high), naïve and memory T cells (low) | Down-regulates Tregs, up-regulates CD8+ effector cells and extends their survival | NCAGN01876 | mAb | I/II | NCT03126110 |
ICOS | Activated cytotoxic T cells, Tregs, NK cells | Enhances T cell functions to foreign antigen | GSK3359609 | mAb | II | NCT03693612 |
4‑1BB | Innate and adaptive immune cells | Upregulates anti-apoptotic molecules, cytokine secretion, and enhanced effector function | Utomilumab (PF-05082566) | mAb | II | NCT02554812 |
CD27 | T cells, NK cells, Tregs | Enhances CD8+ T cell activation, survival and effector function | Varlilumab (CDX-1127) | mAb | I/II | NCT03617328 |
CD40 | APCs, DCs, B cells, non-immune cells and tumors | Regulates initiation and progression of cellular and humoral adaptive immunity | APX005M | mAb | II | NCT04337931 |
Other pathways and targets | ||||||
IDO | Overexpressed in several malignancies, including melanoma | Inhibits immune cell effector functions and/or facilitates T cell death | Linrodostat (BMS-986205) | Small molecule inhibitor | III | NCT03329846 |
CD73 | Overexpressed by many cancer cells | Inhibits immunosurveillance against tumor cells by upregulating adenosine signaling | LY3475070 | Small molecule inhibitor | I | NCT04148937 |
TLR | Expressed on a variety of cell types | Play a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules | Poly-ICLC (Hiltonol) | Viral mimic immunostimulant | I/II | NCT03617328 NCT04364230 |
IL-2R | Lymphocytes | Plays vital roles in key functions of the immune system, tolerance and immunity | Bempegaldesleukin (NKTR-214) | PEGylated IL‑2 | III | NCT04410445 NCT03635983 |
IL-10 | Produced by almost all cell types within the innate and adaptive immune system | Multiple, pleiotropic effects in immunoregulation and inflammation | Pegilodecakin (LY3500518, AM0010) | PEGylated IL-10 | I | NCT02009449 |
Oncolytic peptides | – | Has the ability to kill human cancer cells and induce specific anticancer immune response when injected locally | Ruxotemitide (LTX-315) | Lytic peptide | I | NCT01986426 |
HDAC | Primarily found in the nucleus (depending on class) | Regulates DNA expression by acetylation and de-acetylation | Entinostat (MS-275, SNDX-275) | Small molecule inhibitor | II | NCT03765229 |
STING | T cells, NK cells, myeloid cells | Plays important role in innate immunity | E7766 | Agonist compound | I | NCT04144140 |
MIW815 (ADU-S100) | Agonist compound | I | NCT03172936 |