Table 9.
Overview of some clinical trials/approvals for targeting chemo/cytokine receptors.
| Target | mAb/agent | Type | Approval/trial status | Reference |
|---|---|---|---|---|
| Cytokine receptors | ||||
| IL-1Ra | Anakinra | RFP | RA, NOMID, phase II RCT for stroke (SQ) | (113, 248) |
| IL-2R-α | Daclizumab | Hz | Relapsing multiple sclerosis (MS) | (249, 250) |
| Basiliximab | C | Anti-t transplant rejection (IV) | ||
| Inolimomab | M | Graft-vs-host disease (phase III trial failed) | ||
| IL-4R-α | Dupilumab | H | Uncontrolled asthma (NCT02948959) | |
| Atopic dermatitis phase III (SQ) | (251) | |||
| IL-5R-α | Benralizumab | Hz | FDA-approved for asthma (SQ) | (252) |
| IL-6R-α | Tocilizumab | RHz | FDA-approved for RA | (253) |
| AE | (254) | |||
| GCA | (255) | |||
| NMO—under study | (256) | |||
| Olokizumab | Hz | RA, phase II | (257) | |
| Sarilumab | H | FDA-approved for RA (SQ) | (184) | |
| Saralizumab | Hz | NMO/NMOSD phase II (NCT02073279) | ||
| IL-6R (m & s) | Satrilumab | H | RA; phase II juvenile idiopathic arthritis (NCT027767) | |
| IL-17R | Brodalumab | H | FDA-approved for psoriasis (SQ) | (258) |
| Il-31Ra | Nemolizumab | Hz | Eczema (NCT03100344) | |
| TNFR2 | Ethanercepta | RFP | RA, JRA, psoriatic arthritis (SQ) | (259) |
| Type 1 IFN-R | Anifrolumab | H | SLE (phase III trial) | (26) |
| GM-CSF-Rα | Mavrilimumab | H | RA, phase IIb; phase III | (15, 260) |
| Chemokine receptors | ||||
| CCR1 | BX471 | Drug | Phase II, failed in MS | (261) |
| CCR4 | Mogamulizumab | Hz | T cell lymphoma | (262) |
| CCR5 | PRO 140 | H | Phase IIa RCT in HIV | (263) |
| Maraviroc | Drug | FDA-approved for HIV infection (not effective in RA) | (264) | |
| CCR9 | CCCX282-B | Drug | Phase II, failed in IBD | (265) |
| CXCR4-α/CXCR7 | Plerixafor (AMD3100) | Drug | FDA-approved immunostimulant to mobilize stem cells in lymphoma, multiple myeloma (SQ) | (266) |
| CXCR4 | Ulocuplumab | H | Solid tumors, failed (NCT02472977) | |
M, mouse; C, chimeric; Hz, humanized; H, human; FP, fusion protein; RH, recombinant humanized monoclonal antibody; RFP, recombinant fusion protein; IL-6R (m & s), membrane-bound and soluble IL-6R; IV, intravenous; SQ, subcutaneous; HIV, human immunodeficiency virus; NOMID, neonatal-onset multisystem inflammatory disease (SQ); AE, autoimmune encephalitis; GCA, giant cell arteritis; NMO, neuromyelitis optica; NMOD, neuromyelitis spectrum disorder; JRA, juvenile rheumatoid arthritis; UC, ulcerative colitis; FDA, U.S. Food and Drug Administration; GM-CSF, granulocyte–monocyte colony-stimulating factor; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TNF, tumor necrosis factor; IBD, inflammatory bowel disease; Ra, receptor antagonist; α, alpha chain (CD25).
acirculating receptor FP, soluble TNFR2 receptor.
Plerixator is a partial agonist at CCR4-α and a full agonist of CXCR7.
Source material was gathered using PubMed.gov searches under numerous search terms without restriction to the year of publication, http://Clinicaltrials.gov under disease headings or specific drugs/agents, and various other online resources.