One downside of the antibody-drug conjugates used in oncology today is that the drug-carrying antibodies can shed much of their toxic cargo on the way to the tumour site. Now, German researchers have published their method for attaching drugs to antibodies with greater stability, potentially making this treatment much safer.
Abi Millar finds out more.
Antibody-drug conjugates (ADCs) hold the potential to change the nature of cancer treatment. Unlike classic chemotherapy – in which a drug is released into the body, killing cancer cells and healthy cells alike – ADCs enable the drug to be transported selectively to the site of action.
In essence, a cytotoxic drug is linked to an antibody, which homes in on a given protein (antigen) found only on tumour cells. Once the antibody has found its target, the tumour cell absorbs the molecule, which releases its toxic payload in the right place. At least in principle, this means killing the cancer while sparing healthy tissue, limiting side effects.
“In addition to being a classical therapeutic antibody, the antibody within ADCs needs to trigger internalisation into the cell upon target binding and maintain a high level of stability,” explains Marc-André Kasper, a researcher at the Leibniz-ForschungsInstitut für Molekulare Pharmakologie (FMP) in Berlin. “Meanwhile, the small molecule payload needs to be highly potent due to low concentrations of ADCs in cells.”
In recent years, there has been much discussion around ADCs, and there are more than 200 drugs of this kind at the clinical or preclinical stage. So far, six have been approved, including four in the past two years, and there are several others at the late stages of development.
Read the rest of this article in the November 2019 edition of Pharma Technology Focus