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In the world of monoclonal antibodies, being small is a big deal. Smaller antibodies and antibody fragments can penetrate solid tumors that would be inaccessible to larger antibodies, and some can even make it across the blood-brain barrier. That’s why it’s exciting that researchers at the University of Bath and UCB (a Belgian biotech company) have designed extra-small antibody fragments from cows.
These novel fragments, known as knob domain peptides, are even smaller than antibodies from llamas and alpacas, which have the unusually small naturally occurring antibodies. These tiny antibody fragments are high in cysteine, the sulfur-containing amino acid that allows proteins to form disulfide bonds between disparate regions of the peptide. The abundance of these disulfide bonds in the knob domain make them more stable than regular mAbs. Furthermore, the researchers showed that these isolated knob domains can autonomously bind antigens the same way that full-sized antibodies do. These developments could pave the way for exciting new progress in antibody therapies.