Abstract
Antibody–drug conjugates are an important and emerging drug class for the treatment of cancer. Recent evidence strongly suggests that site-specific drug conjugation results in a homogenous population of molecules with more favorable activity and pharmacokinetic properties than randomly conjugated antibodies. Unnatural amino acids (uAAs) can be incorporated in recombinant proteins to enable unique orthogonal chemistries in comparison to the side chains of the natural 20 amino acids. Thus, uAAs present a novel platform for which to create next-generation antibody–drug conjugates. Furthermore, site-specific conjugation through uAAs can also enpower unique small molecule, bispecific, multispecific and other conjugates that could be important constructs for therapeutics, diagnostics and research reagents. Here, we review the progress in uAA incorporation and conjugate construction through both cell-based and -free approaches.
Financial & competing interests disclosure
T Hallam owns stock in Sutro Biopharma, and is developing unnatural amino acid technologies with which to conjugate cytotoxic drugs to antibodies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.