At present, for the immunotherapy of rheumatoid arthritis, five different TNF inhibitors, one inhibitor of IL-1 and of IL-6, as well as one B- and one T-lymphocyte-targeting molecules are available.
Etanercept: Etanercept was the first TNF inhibitor approved by the US FDA in 1998 for use in rheumatoid arthritis. In comparison with other TNF inhibitors, etanercept is not an antibody, but a recombinant human soluble fusion protein, functioning as a decoy receptor and, therefore, inhibits the binding of TNF-a to its regular receptor.
Infliximab: Inf liximab was the second biologic agent approved by the FDA for treatment of rheumatoid arthritis, and is a chimeric murine–human IgG1 monoclonal antibody against TNF-a, which binds to both circulating and transmembrane TNF-a.
Adalimumab: A few years after approval of etanercept and infliximab for therapy of rheumatoid arthritis, adalimumab was the second TNF inhibitor administered by subcutaneous injection, and the first fully human monoclonal antibody binding to TNF. The advantage of adalimumab is a less frequent injection interval of every other week.
Golimumab: In 2009, golimumab was approved by the FDA as a monthly subcutaneous injection for the treatment of moderate-to-severely active RA. Golimumab is a human monoclonal antibody with a half-life of approximately 2 weeks, which binds to soluble and transmembrane forms of TNF-a to inhibit its biologic activity.
Certolizumab pegol: The new story behind certolizumab pegol was that this compound is an Fc-free humanized pegylated anti-TNF Fab' fragment, with a different mechanism of action compared with other TNF inhibitors. The different structure might be an explanation for the possibly higher efficiency of certolizumab pegol in comparison with other TNF inhibitors in recent indirect comparison studies.
Anakinra (IL-1 inhibitor): Owing to high circulating plasma levels of IL-1b and their correlation with clinical disease
activity in patients with rheumatoid arthritis, IL-1b was thought to play a central role in the pathogenesis of rheumatoid arthritis. Anakinra, a recombinant human IL-1 receptor antagonist, is the only therapy for rheumatoid arthritis that targets IL-1. Anakinra, which was approved by the FDA in 2001, was the first non-anti-TNF biologic at that time.
Tocilizumab (IL-6 receptor inhibitor): In January 2010, the FDA approved tocilizumab for the treatment of rheumatoid arthritis. Tocilizumab is a humanized recombinant IgG1 monoclonal antibody binding to both soluble and membrane- bound IL-6 receptors. It is administered as intravenous infusion every 4 weeks; an additional approval of a subcutaneous injection is sought for the future.
Rituximab: Rituximab is a chimeric anti-CD20 monoclonal antibody that depletes CD20-positive B cells. Initially, it had been approved for the treatment of B-cell lymphomas in 1997, until approval by the FDA was given in 2006 for the use in adult patients with moderate-to-severe rheumatoid arthritis, who have not responded adequately to TNF antagonists.
Abatacept: Abatacept is approved as mono- or combination-therapy with other non-biological antirheumatic drugs for the treatment of moderate-to-severely active rheumatoid arthritis. In contrast with other biologics, it is a recombinant human soluble fusion protein of the extracellular domain of human CTLA-4 and an Fc domain of human IgG1. Abatacept selectively modulates the costimulation of T lymphocytes by inhibiting their activation through binding to CD80/CD86 and thereby preventing the interaction with CD28 expressed on T cells. Additionally, it is the only biologic agent in rheumatoid arthritis at the moment that can be administered either by subcutaneous injection (once a week) or intravenous infusion (every 4 weeks).
Many research on immunotherapy for rheumatoid arthritis are going on, making a new era for this treatment.
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Carcinoembryonic antigen cell adhesion molecule, CEACAM5 (CEA, CD66e) is a well known tumor marker, in particular in colorectal carcinomas, where circulating CEA is used to monitor response to chemotherapy. This GPI anchored glycoprotein belongs to the CEA-related cell adhesion molecule (CEACAM) family and shares domains identity to other members, like CEACAM6. CEA is highly expressed at the surface of tumor cells in several epithelial tumors, including CRC, lung and gastric tumors and displays a limited expression in normal tissue where it is found solely at the luminal surface of columnar absorptive cells. This prompted us to develop an anti-CEA antibody-drug conjugate (ADC) for the treatment of CEA-positive tumors.
Eisenberg G et al. Transcutaneous immunization with hydrophilic recombinant gp100 protein induces antigen-specific cellular immune response[J]. Cellular immunology, 2010, 266(1): 98-103.
Brayman M et al. MUC1: a multifunctional cell surface component of reproductive tissue epithelia[J]. Reproductive Biology and Endocrinology, 2004, 2(1): 4.