Over the last two decades researchers have been able to significantly advance the molecular sophistication and clinical efficacy of antibody-drug conjugates. Initial research was primarily focused on humanizing antibody proteins to overcome problems of immunogenicity. Ongoing research makes targeting cancer with antibody-drug conjugates or ADCs possible.

The initial research was also designed to expand the target antigen repertoire. In parallel to naked monoclonal antibodies, antibody-drug conjugates (ADCs) have been developed to target the delivery of highly potent cytotoxic anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy.  This and ongoing research has made a new generation of ADCs possible. [1-4]

With more clinically relevant choises of target antigens and more potent cytotoxic agents, the potential of ADCs has been enhanced by several factors.  [2,3,5] Furthermore, new potent cytotoxic agents in conjugation with new linkers with improved stability have also contributed to more ADCs.

Fig 1.0. Monomethyl Auristatin E (MMAE) based Antibody-drug Conjugate. The antibody-drug conjugates or ADC binds to a tumor-specific antigen at the tumor cell surface via FAB. Following this step, the ADC is internalized into the tumor cell (-> Lysosomes). Toxophor is then released from the antibody (via lysosomal peptid cleavage). Finally, the toxophor kills cells through inhibition of tubulin polymerization

Better understanding
Greater understanding and knowledge of advanced antibody-drug conjugate technology, cancer biology, and pharmacology has made the development of new ADC possible. The understanding of what is involved in targeting different cancers with ADCs and  the potential methods for doing so has also improved. Researchers have been able to create new monoclonal antibodies specific for the preferentially expressed antigen and linking them to appropriate cytotoxics [6,7] They have however, also been able to ‘upgrade’ existing monoclonal antibodies to deliver a potent cytotoxic directly to tumor cells. [2,6]

Ongoing research has shown that combining antibody-drug conjugates with conventional chemotherapeutic agents may be advantageous under certain clinical conditions. Preclinical studies suggest this may be due to multiple mechanisms of action, including the anticancer effect of the ADC on the target cells, the effect of the chemotherapy on the stromal cells and, in some cases, a combination of these mechanisms. [2,8]

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ADC Review
ADC Review, Journal of Antibody-drug Conjugates (ISSN 2327-0152) launched in 2013, is designed to serve the needs of a diverse community of individuals including academia, life sciences, pharma, (basic, translational and clinical) research, clinicians/physicians, along with regulatory affairs, government authorities and representatives from payers, and policy makers. The Journal’s content includes peer reviewed research, commentaries, news features, discussions, editorials and blogs on topics relevant to a broad international readership. The Journal also offers a knowledge center (called ADC University) offering the latest and most relevant information about Antibody-drug Conjugates (ADCs), BiSpecific Antibodies, Site Specific Antibody Drug Conjugates, Small Molecule Drug Conjugates (SMDC), and Engineered Antibody Fragments. The purpose of the Journal is to present this information in an understandable and a useful format for all stakeholders.