Our Science

Delivering on the promise of science by advancing next‑generation ADCs

ADC Therapeutics is advancing next-generation antibody drug conjugates (ADCs) with highly potent and targeted pyrrolobenzodiazepine (PBD) dimer technology. These proprietary PBD-based ADCs are expected to provide a novel way to treat hematologic cancers and solid tumors. In addition to our PBD technology, we are expanding our ADC platform with new antibody constructs and payloads. Our researchers intend to fully pursue all avenues to develop new and differentiated assets to address significant unmet medical needs and improve the lives of patients with cancer.

Advancing antibody drug conjugates with PBD-dimer technology

  • 1
    Binding and internalization
    The antigen-targeted antibody binds to a specific tumor cell surface antigen and internalizes the drug conjugate

  • 2
    DNA cross-linking
    The potent PBD dimer is released inside the cell, where it then creates a covalent cross-link between the strands of the DNA double helix

  • 3
    Tumor cell death
    Because these cross-links do not trigger DNA repair, they are invisible to repair mechanisms and can covertly persist to interrupt cell division and cause tumor cell death

Our Technology

A novel class of PBD dimers

ADC Therapeutics’ proprietary ADCs are highly targeted drug constructs that combine monoclonal antibodies specific to surface tumor targets with a novel class of highly potent PBD dimer toxins.

Less visible to DNA repair mechanisms

After the antibody binds to a specific tumor cell surface antigen and the ADC is internalized, the cytotoxic PBD dimer is designed to be released inside the cells where it binds in the minor groove of double-helix DNA, forming potent cytotoxic DNA interstrand cross-links. The cross-links formed by the PBD dimer are designed to block cell division and kill the cancer cells. PBD dimers do not distort the DNA structure, which makes them invisible to repair mechanisms and allows the cross-links to persist within the DNA.

Designed for reduced drug resistance

Unlike earlier generation PBD chemistry, these proprietary PBD dimers are not a substrate for multi-drug resistance proteins—even in hard-to-treat tumors.

“PBDs cross link in the DNA of cancer cells, enabling them to elude DNA repair/cancer resistance mechanisms. This allows for a longer lasting effect on cancer cells.”
— Patrick van Berkel, PhD, Chief Scientific Officer

Patrick van Berkel