TGN1412 analysis in The Lancet

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A paper by Marcel Kenter and Adam Cohen published in this week's issue of The Lancet (Establishing risk of human experimentation with drugs: lessons from TGN1412; cached here for 1 week) comes to essentially the same conclusion that I and others did back in March: there was too much data missing from TeGenero's documentation, which should have affected the risk analysis of the human trial of TGN1412.

The paper highlights the suspected differences in antibody binding affinity between human and monkey CD28. However, according to the paper:

On July 3 and 13, 2006, roughly 4 months after the TGN1412 clinical trial and during the process of bankruptcy, TeGenero submitted two identical cynomolgus [Macaca fascicularis] CD28 nucleotide sequences to the NCBI database (accession numbers ABG77997 and ABG77998) potentially coding for a CD28 molecule with an extracellular domain identical to the human counterpart.

Additionally, on July 25th, another group submitted the complete coding sequence and derived protein sequence for cynomolgus CD28 to Entrez. Comparing this sequence (which is identical to that posted by TeGenero) to the Homo sapiens CD28 protein sequence shows only two amino acids difference: these two amino acids are shared with the Rhesus macaque, but both are found in the transmembrane region of the protein and not in any of the residues thought to be in contact with the TGN1412 antibody.