Antibody-Drug Conjugates Overview

Antibody-Drug Conjugates Overview

Published by BroadPharm on July 21, 2021

Antibody-Drug Conjugates (ADCs) are a class of targeted drugs composed of a drug linked to an mAbs (antibody) that is designed to specifically release their payload at a tumor.

When designed ADCs there are several features of the cancer and the compound that needs to be concerned: choosing monoclonal antibodies based on a certain type of tumor-associated antigen, linkers, and payloads. Figure 1 illustrates the considerations for ADC development.

diagram of antibody drug conjugate linker as well as a description
    • Targets a well-characterized antigen with high tumor expression
    • Has limited interaction with normal tissue expression
    • Minimal nonspecific binding
    • Maintains stability, binding, internalization, etc.
      Attachment site
    • Typically occurs through nonspecific modification of cysteine or lysine residues
    • Mixture of conjugates with variable payload to antibody ratios
    • Site-selective conjugation technologies can produce more homogenous ADCs
    • Stable in circulation
    • Selective intracellular release payload, via cleavable or non-cleavable linkages
    • Highly potent
    • Non-immunogenic
    • Can be modified to allow for linker attachment
    • A well-defined mechanism of action
Figure 1. There are four key components of an ADC compound; the antibody used, the attachment site for the linker, the linker structure, and the payload to be delivered.

The antibodies are selected for their binding to specific antigens that are generally more numerous on the surface of cancer cells than healthy cells.

The linkers holding the cytotoxic drug to the antibody needs to be resilient enough to stay together during the journey to the tumor while not inhibiting the payload once inside the cell.

The active payload may act by either microtubule inhibition or DNA damage/entanglement. The inherent potency of the released drug must be sufficient to kill the tumor cells at a low concentration.

This means that very potent drugs with sub-nanomolar IC50 are typically used that are 100-1000-fold more potent than traditional anticancer agents. This type of targeting with small quantities of highly potent payloads is designed to limit side effects and provide a wider therapeutic window than other chemotherapeutic agents.

Figure 2 shows the 6 steps that occur with ADC drugs once they are inserted into a patient's body as well the potential problems that must be addressed in designing an ADC drug.

Diagram of the ADC drug process
Figure 2. This image depicts the six steps of ADC interaction with a cancerous cell that led to apoptosis. Image taken from Bioscience Reports 35(4).

As a worldwide leader of bioconjugation linker, BroadPharm offers a wide array of different ADC Linkers to empower our customer's advanced research. These compounds feature great aqueous solubility, smart choice of PEG length, and a broad selection of functional groups to choose from.

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