New immunosuppressive therapies in renal transplantation: monoclonal antibodies.
Remarkable advances in understanding the mechanisms of immune recognition and allograft rejection have been made in the past few years, leading to the development of innovative immunosuppressive strategies in the field of renal transplantation. Monoclonal antibodies (mAbs) have emerged as a new class of immunosuppressive agents, which appear to be effective (in both the treatment and the prevention of acute rejection) and well-tolerated in renal transplant recipients. The highly specific effects of these drugs make them less toxic than the oral long-term maintenance agents such as corticosteroids and the calcineurin inhibitors. Some of these mAbs have already confirmed their efficacy in preventing acute rejection in clinical phase III studies, and are now part of the well-established immunosuppressive regimens; these are the anti-CD25 mAbs (basiliximab and daclizumab). Other recently developed mAbs, like anti-CD52 (Campath-1H), anti-CD20 (rituximab), anti-LFA-1, anti-ICAM-1 and anti-tumour necrosis factor (TNF)-alpha (infliximab), are currently being tested, and show encouraging immunosuppressive potential. Blocking either the binding of cell-surface molecules or intracellular signal transduction, these mAbs could become an effective method to promote the holy grail of solid-organ transplantation, antigen-specific tolerance.
Buhaescu
Irina
I
Dialysis and Renal Transplantation Center, Parhon University Hospital, Iasi--Romania. irinabuhaescu@yahoo.fr
Segall
Liviu
L
Goldsmith
David
D
Covic
Adrian
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D000943:Antigens, Differentiation / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D000074301:CD52 Antigen; D060908:CTLA-4 Antigen; D006023:Glycoproteins / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016030:Kidney Transplantation / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D000069285:Infliximab