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

It is marketed under the brand name Nulojix, manufactured by BMS. [source, 2012]
Belatacept (LEA29Y) is another human CTLA-4 Ig that differs from Abatacept by substitution of two amino acids, which confers a stronger binding avidity to B7 and a greater inhibition of T-cell activation. [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]
Serum LEA29Y concentrations were determined by sandwich ELISA using 1 μg/mL monoclonal anti–human-CTLA-4 antibody (Beckmann Coulter) and horseradish peroxidase–conjugated polyclonal rabbit anti-human IgG (Dako). [source, 2012]
Transgenic pigs displayed a strong LEA29Y staining in the pancreatic islets (Fig. 1). [source, 2012]
Immunohistochemical staining of the subcapsular graft revealed maturation of the transplanted ICCs toward a strongly insulin-expressing endocrine tissue in both transplantation groups with LEA29Y transgene expression restricted to the grafts of Tx, LEA-tg mice (Fig. 2). [source, 2012]
LEA29Y concentrations in the plasma of normoglycemic Tx, LEA-tg mice were 270 ± 24 ng/mL. [source, 2012]
The finding that transgenic ICCs had strong LEA29Y expression and were able to normalize blood glucose levels raised the question whether these ICCs were protected from graft rejection after reconstitution with human PBMCs. [source, 2012]
In contrast, in all mice transplanted with LEA29Y transgenic ICCs, the area under the glucose and insulin curve during IPGTT was comparable before and 27 d after transfer of human PBMCs (Fig. 3). [source, 2012]