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

The expression cassette is composed of the Rous Sarcoma Virus (RSV) promoter that drives the expression of the immunosuppressive LEA29Y (belataceptĀ®) protein. [source, 2011]
Primers and TaqMan probes used for the amplification of vector-specific sequence (LEA29Y) and of endogenous macaque sequence (macaque Īµ-globin gene), as well as Q-PCR conditions were previously described by Toromanoff et al. [2]. [source, 2011]
The rAAV vector expression cassette used here encodes the LEA29Y molecule under the control of the RSVp (Fig. 1a). [source, 2011]
The LEA29Y molecule was detected in the serum of the animals at different time points as previously published in Toromanoff et al. [2] for Mac 1 and Mac 2, and in Penaud-Budloo et al. [4] for Mac 9. [source, 2011]
The LEA29Y concentration in the serum of the IV-injected animals (Mac 10 and 11) was below the sensitivity threshold of the ELISA assay (data not shown). [source, 2011]
We have previously shown that the rAAV-mediated expression of the LEA29Y transgene under the RSVp transcriptional control was stable for more than 2 years in IM injected primates (Mac 1, 2, and 9) [4]. [source, 2011]
Since LEA29Y is a secreted protein, we could not correlate the methylation status of rAAV genomes with the local transgene expression by assessing the protein level. [source, 2011]
Considering that most of the vector genomes were detected in the muscle and the liver after IM administration of rAAV vectors (Le Guiner et al., unpublished data), the majority of the LEA29Y protein expression derives from the injected skeletal muscle. [source, 2011]
Furthermore, potent immunosuppression has been observed with a high-affinity variant of CTLA-4Ig, LEA29Y (belatacept; Larsen et al., 2005). [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]