Table 2.
Biologics targeting immunomodulatory pathways in clinical trials
| Name | Companies | Type of biologic | Pathways | Roles | Indications | Trial phase |
|---|---|---|---|---|---|---|
| Immunoglobulin family | ||||||
| Tremelimumab | Medlmmune/AstraZeneca | CTLA4-specific human IgG2 | CTLA4-B7.1, CTLA4-B7.2, B7H2 | T cell priming and activation | Solid tumours | II |
| Galiximab | Cancer and Leukemia Group B (CALGB)/Biogen Idec |
B7.1-specific chimeric IgG1 | B7.1 | B cell proliferation | Lymphoma | II |
| BMS-936558 | Bristol-Myers Squibb/Medarex | PD1-specific human IgG4 | PD1-B7H1, PD1-B7DC | T cell activation and tolerance | Multiple cancers; HCV | III |
| CT-011 | CureTech | PD1-specific humanized IgG1 | PD1-B7H1, PD1-B7DC | T cell activation and tolerance | Advanced solid tumours; HCV | II |
| MK-3475 | Merck/Schering-Plough | PD1-specific IgG4 | PD1-B7H1, PD1-B7DC | T cell activation and tolerance | Advanced or metastatic solid tumours | I |
| AMP224 | Amplimmune/GlaxoSmithKline | B7DC and human IgG1 fusion protein | PD1-B7H1, PD1-B7DC | T cell activation and tolerance | Multiple cancers | I |
| BMS-936559 | Bristol-Myers Squibb | B7H1-specific human IgG4 | PD1-B7H1 | T cell activation and tolerance | Advanced or recurrent solid tumours | I |
| MPDL3280A | Genentech/Roche | B7H1-specific engineered human IgG1 | PD1-B7H1 | T cell activation and tolerance | Solid tumours | I |
| MEDI4736 | Medlmmune/AstraZeneca | B7H1-specific engineered human IgG1 | PD1-B7H1 | T cell activation and tolerance | Solid tumours | I |
| MEDI-570 | Medlmmune/AstraZeneca | ICOS-specific human IgG | ICOS-B7H2 | T cell-dependent B cell response | SLE | I |
| AMG 557 | Amgen | B7H2-specific human IgG | ICOS, CD28, CTLA4 | T cell-dependent B cell response | SLE, psoriasis | I |
| MGA271 | Macrogenics | B7H3-specific, ADCC-enhanced humanized IgG1 | B7H3 | T cell activation and tolerance | Solid tumours | I |
| IMP321 | Immutep | LAG3 and human IgG1 fusion protein | LAG3-MHCII | DC maturation and T cell activation | Multiple cancers | I/II |
| TNF family | ||||||
| BMS-663513 | Bristol-Myers Squibb | CD137-specific human IgG4 | CD137 | T cell activation | Solid tumours | I/II |
| PF-05082566 | Pfizer | CD137-specific human IgG | CD137 | T cell activation | Lymphoma | I |
| CDX-1127 | Celldex | CD27-specific human IgG1 | CD27 | T cell activation | Multiple cancers | I |
| Anti-OX40 | Providence Health & Services | OX40-specific mouse IgG | OX40 | CD4 T cell activation | Prostate cancer | II |
| huMAb OX40L | Genentech/Roche | OX40L-specific human IgG1 | OX40-OX40L | CD4 T cell activation | Asthma | II |
| TRX518 | GITR Inc. | GITR-specific humanized IgG1 | GITR-GITRL | T cell activation | Solid tumours | I |
| Atacicept | ZymoGenetics/EMD Serono | TACI and human IgG1 fusion protein | TACI, BCMA and BAFFR | B cell activation and antibody production | SLE, rheumatoid arthritis, multiple sclerosis and optic neuritis | II/III |
| CP-870,893 | Pfizer | CD40-specific human IgG1 | CD40 | APC activation and B cell maturation | Multiple cancers | I |
| Lucatumumab | Novartis | CD40-specific human IgG1 | CD40 | APC activation and B cell maturation | Lymphoma and leukaemia | I/II |
| Dacetuzumab | Seattle Genetics | CD40-specific humanized IgG1 | CD40 | APC activation and B cell maturation | Lymphoma and multiple myeloma | II |
ADCC, antibody-dependent cell-mediated cytotoxicity; APC, antigen-presenting cell; B7H1, B7 homolog 1; BAFFR, B cell activation factor receptor; BCMA, B cell maturation antigen; CTLA4, cytotoxic T lymphocyte antigen 4; DC, dendritic cell; GITR, glucocorticoid-induced TNFR-related protein; GITRL, GITR ligand; HCV, hepatitis C virus; ICOS, inducible co-stimulator; IgG1, immunoglobulin G1; LAG3, lymphocyte activation gene 3; MHCII, major histocompatibility complex class II; OX40L, OX40 ligand; PD1, programmed cell death protein 1; SLE, systemic lupus erythematosus; TACI, transmembrane activator and CAML interactor; TNF, tumour necrosis factor.