Abstract
In the era of precision medicine, antibody-based therapeutics are rapidly enriched with emerging advances and new proof-of-concept formats. In this context, antibody-drug conjugates (ADCs) have evolved to merge the high selectivity and specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of attached payloads. So far, ten ADCs have been approved by FDA for oncological indications and many others are currently being tested in clinical and preclinical level. This paper summarizes the essential components of ADCs, from their functional principles and structure up to their limitations and resistance mechanisms, focusing on all latest bioengineering breakthroughs such as bispecific mAbs, dual-drug platforms as well as novel linkers and conjugation chemistries. In continuation of our recent review on anticancer implication of ADC’s technology, further insights regarding their potential usage outside of the oncological spectrum are also presented. Better understanding of immunoconjugates could maximize their efficacy and optimize their safety, extending their use in everyday clinical practice.
Highlights
Antibody-drug conjugates (ADCs) comprise a fast-expanding therapeutic modality designed to target disease cells, sparing the adjacent healthy tissues
ADCs are essentially tripartite pro-drugs consisting of an antibody tethered via a chemical linker to a given payload [1]. (Figure 1) After their administration, these agents circulate as inactive assemblies which are eventually catabolized via endogenous cleavage mechanisms at the intracellular compartment of the targeted cell [2]
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Summary
Antibody-drug conjugates (ADCs) comprise a fast-expanding therapeutic modality designed to target disease cells, sparing the adjacent healthy tissues. ADCs are essentially tripartite pro-drugs consisting of an antibody tethered via a chemical linker to a given payload [1]. The clinical utility of ADCs has been mainly explored in hematological/oncological indications [1]. Brentuximab vedotin (BV), ABBV-3373, and DSTA4637S are currently under clinical testing for non-oncological indications, such as autoimmune and infectious diseases [4,5,6]. We elaborate on the functional principles and the characteristics of these components (Box 1), with emphasis on the latest bioengineering advances, such as bispecific antibodies, multi-drug ADCs, non-internalizing ADCs, and ADC-antibody co-administration.
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