Molecular Target | Reagent | Principle | Company/Reference | Experimental Effects | Clinical Trial/Status |
---|---|---|---|---|---|
TRAIL receptors | HGS-ETR1 | Agonistic TRAIL-R1 mAb | HGSI/CAT | Apoptosis induction in various tumor cell lines and tumor xenografts, synergistic with anticancer drugs | Phase 2, no hepatic or hematological toxicity with up to 10 mg/kg i.v. |
HGS-ETR2 | Agonistic TRAIL-R2 mAb | HGSI/CAT | Apoptosis induction in tumor cell lines | Phase 1 | |
HGS-TR2J | Agonistic TRAIL-R2 mAb | HGSI/KNBWY | Apoptosis induction in tumor cell lines | Phase 1 | |
PRO1762 | Soluble human Apo2L/TRAIL | Amgen/Genentech | Apoptosis induction in tumor cell lines, no side effects in cynomolgus monkeys and mice, synergistic with anticancer drugs | Phase 1 | |
TRA-8 | Agonistic TRAIL-R2 mAb | Sankyo Co., Ltd. | Apoptosis induction in tumor cell lines | Preclinical | |
CD95/Fas | CD95-Fc | Humanized CD95 Fc-decoy construct | ApoGenix | Inhibition of CD95 signaling | Preclinical, first intended for spinal cord injury |
TNF | Recombinant TNF-α | Combination of TNF and chemotherapy | Eggermont and ten Hagen, 2001 | Apoptosis induction in tumor-associated blood vessels | Approved for isolated limb perfusion therapy in melanoma |
HUMIRA (Adalimumab) | Recombinant human IgG1κ mAb against TNF-α | CAT/Abbott | Inhibition of TNF-α | FDA approved for rheumatoid arthritis, psoriasis, ankylosing spondylitis, and Crohn's disease | |
Infliximab (Remicade) | Mouse/human TNF-α antibody | Centocor/Schering-Plough | Anti-inflammatory, also induces apoptosis in macrophages | FDA approved for rheumatoid arthritis and Crohn's disease | |
Enbrel (Etanercept) | Recombinant TNF-R2/IgG fusion protein | Amgen/Wyeth | Anti-inflammatory in rheumatoid arthritis, Crohn's disease, and other inflammations | Approved for United States, some patients with severe side effects (infections, neurologic, and hematologic disorders) | |
CDP571 | Mouse/human TNF-α antibody | Celltech | Disappointing results in Crohn's disease | Phase 3 for rheumatoid arthritis stopped | |
ISIS 104838 | 2′-O-Methoxyethyl antisense construct against TNF-α | ISIS | Improvement of rheumatoid arthritis-associated symptoms | Phase 2 for rheumatoid arthritis, Crohn's disease, psoriasis |
Companies: Abbott Laboratories (www.Abbott.com), Amgen (www.amgen.com), ApoGenix (www.apogenix.de), CAT (Cambridge Antibody Technology, www.cambridgeantibody.com), Centocor (www.centocor.com), Celltech Group (www.celltechgroup.com), Genentech (www.gene.com), HGSI (Human Genome Science, Inc., www.hgsi.com), ISIS Pharmaceuticals (www.isispharm.com), KNWBY (Kirin Brewery Company Ltd., www.kirin.com), Sankyo Co., Ltd. (www.sankyo.co.jp), Schering-Plough (www.sch-plough.com), Wyeth (www.wyeth.com).