Abstract
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.
Highlights
Chemotherapeutic strategies have long been used as the primary treatment against a broad range of cancers
Huge efforts have been made to merge the positive features of chemical and biological cancer treatments with the development of antibody drug conjugates (ADCs) that deliver the highly cytotoxic drugs directly at the tumor site
Ever since it was shown that site-specific conjugation positively influences the characteristics of ADCs, the field has rapidly adapted and a significant number of novel techniques has emerged for drug loading at defined location within the antibody
Summary
Chemotherapeutic strategies have long been used as the primary treatment against a broad range of cancers. A different approach to reduce heterogeneity of cysteinebased conjugated ADCs is the engineering of additional cysteine residues to the antibody leaving the interchain disulfides untouched [23, 24]. Neri and coworkers engineered a cysteine residue to the N-terminus of recombinant antibodies and used a thiazolidine linker to site- conjugate the drug cemadotin.
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