How do ADCs work?

Ado-trastuzumab emtansine (Kadcyla)
Ado-trastuzumab emtansine (Kadcyla), known as T-DM1 during clinical trials.

The antibody drug conjugate or ADC is a three-component system including a potent cytotoxic anticancer agent linked via a biodegradable linker to an antibody. The antibody binds to specific markers (antigens or receptors) at the surface of the cancer cell. The whole antibody-drug conjugate is then internalized within the cancer cell, where the linker is degraded and the active drug released.

Fig 1: Antibody drug Conjugates are a new class of therapeutics.  They consists of a cytotoxic agent covalently linked to a monoclonal antibody.

ADCs make use of antibodies that are specific to cell surface proteins and are able to offer various advantages over current chemotherapeutics, including improved target specificity and potency.  While this approach is successful in hematological malignancies, it has some limitations in the treatment of solid tumors.

Lonza
MabPlex
ADC Bio
 

The focused delivery of the cytotoxic agent to the tumor cell is designed to maximize the anti-tumor effect of ADCs, while minimizing its normal tissue exposure, potentially leading to an improved therapeutic index. [1]

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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.