Belatacept: a new biological agent for maintenance immunosuppression in kidney transplantation

Abstract

Despite the increased incidence and severity of acute rejection with belatacept in Phase II and III studies, a better preservation of GFR and reduced incidence of chronic allograft nephropathy was observed as compared with CNIs. Patient and graft survivals were similar over 3- and 5-year follow-up post-transplantation. Incidence of adverse events were similar between the groups, but the risk of post-transplant lymphoproliferative disorder, predominantly involving CNS, was higher in Epstein-Barr virus seronegative recipients on belatacept, especially with a more intensive regimen. CV and metabolic end points were more favorable in belatacept versus CNI groups with similar incidences of diabetes after transplantation. Belatacept seems to be a promising drug for the future, but long-term outcomes are awaited.

New immunosuppressive agents in pediatric transplantation

“…It is a fully human fusion protein of the CTLA4 extracellular domain with fragments of the Tc domain of human IgG1, and it has a binding affinity to CD86/CD80 on the antigen-presenting cell, thus resulting in the blockade of T-cell activation (32,33). The activation of T cells involves the presentation of a peptide by an antigen-presenting cell to the T cell receptor, followed by costimulatory associations between the ligands on the antigen-presenting cell and T cell receptors (33).…”

“…The activation of T cells involves the presentation of a peptide by an antigen-presenting cell to the T cell receptor, followed by costimulatory associations between the ligands on the antigen-presenting cell and T cell receptors (33). In addition, belatacept indirectly inhibits antigen-specific antibody (IgG, IgM, and IgA) production by B lymphocytes, resulting in lower mean immunoglobulin concentrations compared with that resulting from cyclosporine-based therapy (32). Belatacept requires intravenous infusion, and the total infusion dose is based on the body weight of the patient.…”

Co-stimulatory blockade with belatacept in kidney transplantation

“…Phase III, BENEFIT-EXT [5] (0 --12 months) n = 543 BENEFIT long-term extension [10] (36 --60 months) n = 456…”

“…Activation of these two signals leads to the expression of IL-2, and a series of steps leading to further propagation of the lymphocytic proliferation, which is signal 3. This eventually results in T-cell-mediated AR [5].…”

From Immunosuppression to Immunomodulation: Current Principles and Future Strategies

“…Recently, LEA29Y belatacept has been introduced to renal transplant patients. It has a 4× higher binding affinity to CD80/CD86 and an approximately 10-fold higher in vitro potency compared to Orenica [18,19]. Other costimulatory molecules that are under investigation are CD40, OX40, 4-1BB, CD30, BTLA, LIGHT, HVEM, ICOS and many others.…”