ADCs at a glance
Antibody-drug conjugates (ADCs) are an advanced class of therapeutic agent, which combine the effects of several biological components and processes, in order to achieve targeted drug delivery to cancer cells.
An antibody forms the ADC scaffold, and actively binds the target receptor expressed by cancer cells, thereby mediating a targeted effect of the drug molecule.
A drug, in the form of a cytotoxic substance is attached to the targeting antibody, thereby arming the antibody with the ability to kill the cancer cells to which it binds. The drug is inactive in circulation, but is activated upon cellular internalization.
A linker, between the antibody and drug compound, may be utilized to enable particular biological effects, such as improved solubility and stability in circulation, or specific mechanisms for release of the cytotoxic compound in particular intracellular compartments.
Last, but not least, a target receptor with suitable molecular properties, and a high cancer specificity to normal tissue, is essential to obtain targeted, ADC-mediated drug delivery to cancer cells.
ADCs are named from the process of attaching, or conjugating, a drug covalently to the targeting antibody.
By combining antibodies with cytotoxic compounds and linkers possessing certain key properties, ADCs which are highly efficient at targeting and killing cancer cells, based on the characteristics of a given type of cancer, can be designed.
A general overview of the mechanism of action of an ADC, is depicted in the figure below.
Each step is explained in more detail in the image slide show below.
Generally, the ADC field has seen steady growth in the recent decade, especially in the context of oncology.
The identification of novel targets, an improved understanding of optimal dosing strategies, as well on-going development and discovery of novel linkers and payloads with improved stability and potency, has led to a continuously improving understanding of the mechanisms underlying successful ADC treatment.
Currently, five ADCs are approved for treatment of patients in the clinic.
Around 80 unique ADC formats, combining different molecular targets and mechanisms of action, are currently in clinical trials, and 100+ unique ADCs are in development at the pre-clinical level. These numbers continue to grow, demonstrating a continued optimism for the ADC drug modality bu drug developers.
The ADCendo team firmly believes that ADCs will play a key role in targeted drug delivery and personalized medicine in the future.