Blinatumomab is a bispecific molecule of very small size made from a single polypeptide chain comprising the variable heavy chain and light chain of an anti-CD3 monoclonal antibody joined to the variable heavy chain and light chain of an anti-CD19 monoclonal antibody. The idea is that the antibody redirects the T-cell lysis to the tumor B-cell.
The BiTE antibody transiently creates a cytolytic synapse between a cytotoxic T-cell and the cancer target cell; in this case a B-cell lymphoma cell. Granules containing granzymes and the pore-forming protein, perforin, fuse with the T-cell membrane and discharge their toxic content leading to the death of the target cellBlinatumomab has a very short serum half-life of only 2-3 hours and therefore must be administered by continuous infusion over 4-8 weeks using portable minipumps.
I read somewhere a while back that this should work especially well on marrow because the small rod shape could get into it better than the larger Y shaped antibodies.
ReplyDeleteGiven the that this is not a tumor cell specific therapeutic, do you have any opinion on effectiveness vs risk that we can expect as this comes into use?
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The specificty comes from the choice of the target antigen. CD19 is fairly specific to B cells and apart from the encephalopathy risk side effects seems to be caused by the relase of cytokines in those with circulating tumor cells.
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