Antibody drug conjugates (ADCs), a promising class of cancer biopharmaceuticals, combine the specificity of therapeutic antibodies with the pharmacological potency of chemical, cytotoxic drugs. Ever since the first ADCs on the market, a plethora of novel ADC technologies has emerged, covering as diverse aspects as antibody engineering, chemical linker optimization and novel conjugation strategies, together aiming at constantly widening the therapeutic window for ADCs. This review primarily focuses on novel chemical and biotechnological strategies for the site-directed attachment of drugs that are currently validated for 2nd generation ADCs to promote conjugate homogeneity and overall stability.
Keywords: Antibody drug conjugates (ADCs); Sortase A; THIOMAB; Tub-tag; drug-antibody ratio (DAR); formylglycine generating enzyme (FGE); microbial transglutaminase (MTG); monomethyl auristatin E/F (MMAE/MMAF); site-specific conjugation; therapeutic window; tubulin tyrosine ligase (TTL); unnatural amino acids (UAA).