Current Protein Conjugation Strategies and Pioneering Anti-Cancer Applications

The escalating global impact of cancer demands targeted and efficient therapies. Many targeted cancer therapeutics have been fostered into the market in recent years. The leading class of targeted therapeutics is monoclonal antibodies (mAbs). The success of mAbs sparked significant interest and subsequently paved the way for the development of various recombinant protein-based products that were conjugated to other compounds to form antibody-drug conjugates (ADCs) for the treatment of cancer. This review explores diverse mAb conjugation strategies and pioneering approaches for cancer applications, to optimize drug delivery through site-directed conjugation, prodrug conjugates and antibody conjugated nanoparticles. It also highlights promising innovations and addresses challenges including stability issues of ADCs, drug resistance, payload retention and some of the shortcomings of ADCs such as limited bioavailability, short serum half-life, and reduced drug buildup caused by obstacles in the tumor environment primarily associated with heightened interstitial fluid pressure (IFP).