Latest research on LEA29Y

Belatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It is approved for the treatment of rheumatoid arthritis. Belatacept selectively blocks the process of T-cell activation. It was developed by Bristol-Myers-Squibb. It differs from abatacept (Orencia) by only 2 amino acids. FDA approved on June 15, 2011.

Latest findings

Thus, a second generation of CTLA4-Ig, LEA29Y, with a better affinity for CD86, was developed. [source, 2015]
Translation of LEA29Y into non-human primate models of renal transplantation showed superior prolongation in graft survival compared to CTLA4-Ig as a monotherapy, and dramatically improved survival when used as part of a combined immunosuppressive regimen including either Mycophenolate mofetil (MMF) and steroids or anti-IL-2R (basiliximab) (63). [source, 2015]
Based on these encouraging results, LEA29Y (belatacept) was moved into clinical trials as the principal component of an immunosuppressive regimen consisting of basiliximab, steroids, and MMF (5). [source, 2015]
Due to approval of belatacept (Nulojix) as immunosuppressant agent in kidney transplantation, the long-term observational extension of the phase II study was already terminated. [source, 2014]
Belatacept (LEA29Y, NULOJIX®, Bristol-Myers Squibb, Princeton, NJ, USA), a fusion protein combining a modified cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) extracellular domain with the constant-region fragment of human immunoglobulin G1, is a first-in-class, selective co-stimulation blocker recently approved for the prophylaxis of organ rejection in adult KTRs [4]. [source, 2013]
CTLA4-Ig (LEA29Y) was prepared from transfected Cos cells in our laboratory. [source, 2013]
A second-generation agent, LEA29Y (belatacept), was recently introduced, and it had a higher affinity for CD80 and CD86 molecules than CTLA4Ig and was found to be more effective than CTLA4Ig when used in initial primate studies [54]. [source, 2013]
More recently, an improved version of Abatacept termed as LEA29Y with respect to higher affinity and avidity than CLTA-4Ig (Belatacept, Bristol-Myers Squibb, NY, USA) was developed and its efficacy was tested in the phase III clinical trial study in kidney transplantation (17-21). [source, 2013]
Abatacept (Orencia, Bristol-Myers Squibb) and belatacept (Nulojix, Bristol-Myers Squibb), fusion proteins composed of CTLA-4 and immoglobulin IgG1, have utilized this mechanism to confer potent inhibition of alloreactive T cell responses. [source, 2012]
This binding difference was crucial to the need of a second generation of CTLA-4-Ig to be developed, which was named LEA29Y or belatacept. [source, 2012]