4 ms·

I was thinking more of larger protein-antibody conjugates and I agree it probably doesn't need to be a whole antibody. Still a lot more to learn, but very exci

• dnautics 11y ago
  If you don't use the whole antibody, the serum half life us capped in the knees because the body gets rid of serum proteins without glycosylation. In the case if antibodies, glycosylation is on the heavy chain FC region. The first protein antibody conjugates were to couple ricin to antibodies in the late 80s. Ricin's warhead polypeptide chain conveniently has a single cysteine residue that they tried to conjugate to antibodies using disulfide exchange. Of course this was not kind to the antibodies, and the structural disruption is very likely one of the reasons this strategy failed miserably. In general the challenge for ADC is that attaching your drug to an antibody is nontrivial, and the titer is tricky. How many of your molecule does it require to take down a cell? 100? 1,000,000? Can you deliver that number of molecules to each cell, that start reliably conjugated to a large molecule, after yield losses as a result of molecular decoupling?