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.

LEA29Y interactions

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]
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]
CTLA4-Ig (LEA29Y) was prepared from transfected Cos cells in our laboratory. [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]
In vitro, FR104 and CTLA4-Ig (LEA29Y) dose-dependently prevented human T cell proliferation to a similar extent in mixed lymphocytes reactions with EC50 at 0.16 and 0.18 micrograms/ml, respectively. [source, 2012]
In Contrast, biweekly administrations of CTLA4-Ig (LEA29Y or Abatacept), which reduces CD28-CD80/86 costimulation as well as CTLA-4-CD80/86 coinhibition, was ineffective to protect mice from severe GVHD, whereas a less intensive protocol of administration (once a week) was partially effective. [source, 2012]
The immunity was not observed when animals were under immunosuppression with either Mycophenolate mofetil plus Prednisone for 3 weeks, or LEA29Y, a mutant of CTLA4-Ig which blocks costimulatory signaling through CD28 pathway that is required for optimal T cell activation (Toromanoff et al., 2008, 2010). [source, 2011]
Therefore, a modification of this antibody was undertaken, with substitution of two amino acids within the B7.2 binding domain, creating a second generation of CTLA4-Ig (LEA29Y), which was shown to have higher affinity to both B7.1 and B7.2, translating into a 10-fold increase in biological potency. [source, 2011]
LEA29Y, later named belatacept (Bristol–Myers Squibb, New York, NY), was tested in non-human primates and showed superior prolongation in renal allograft survival as monotherapy, when compared with the first-generation CTLA4-Ig, and led to a marked improvement in survival when used in combination with other immunosuppressive regimens such as Mycophenolate mofetil and steroids, or an Anti-IL-2 receptor antibody. [source, 2011]