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 indications

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]
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]
Previous transplantation studies in rats and nonhuman primates using high doses of belatacept for systemic immunosuppression also have shown that costimulatory blockade by LEA29Y does not exert any adverse effects on β-cell function (5,11). [source, 2012]
LEA29Y serum concentrations in recipients of LEA-tg ICCs were ~100–150 times lower as compared with systemic LEA29Y treatment in clinical trials (belatacept, BMS-224818), suggesting that graft protection is primarily mediated by local and not systemic LEA29Y immunomodulatory effects. [source, 2012]
Additional transplantation studies using larger groups of mice with a stably transferred human immune system (22) will be conducted to investigate the long-term effects of LEA29Y transgenic islets on xenogeneic graft rejection. [source, 2012]