Technology-Mediated Functionalization of Proteins and Antibodies Using a Continuous Flow Microreactor

The therapeutic index of conventional chemotherapeutic techniques is narrow and treatment results in a variety of systemic issues. Antibody-drug conjugates represent a targeted delivery method of highly potent cytotoxic payloads to cell surface antigens overexpressed on cancer cells. In recent years, a large number of antibody-drug conjugates have entered clinical trials for the treatment of an assortment of cancers. One of the major limitations in the search for ideal antibody-drug conjugates is the inability to consistently conjugate cytotoxic payloads to antibodies. Conventional conjugation techniques result in heterogeneous mixtures that can aggregate or cause other toxicity. Design of the synthetic linker that joins the toxin and antibody is also crucial; the payload must selectively cleave once internalized by the cell and not in the bloodstream or other organs. The results of the investigation into linker chemistry and the applicability of continuous flow microreactor technology as a viable alternative for the functionalization of proteins is reported herein, including the coupling of antibody-drug conjugates.