Tagworks Pharmaceuticals in the University of Nijmegen Medical Center has developed a new technology that targets tumor to deliver chemotherapy drugs in extreme cases. By controlling the “click release” of a chemotherapeutic drug from its binding to a tumor carrier, the researcher can activate the released drug at the correct location for treatment. The company published their latest research on mice in Nature Communications.
Image source: Nat Commun
Antibody drug conjugates (ADCs) are relatively new anticancer drugs, consisting of an antibody conjugated with tumor killing chemotherapeutic drug. In general, the antibody targets and binds to cellular receptors. However, the antibody on the ADC is mainly used to specifically bind to extracellular receptors of tumor cells. The drug is released after the receptor delivers the entire structure into the cell, and then the chemotherapeutic drug acts in the cell.
ADCs are now used to treat lymphoma and metastatic breast cancer. “These ADCs work very well,” said Marc Robillard of Tagworks Pharmaceuticals, “But for many other tumors, including colorectal and ovarian cancer, these methods are not applicable because there are not many tumor-specific receptors that can automatically capture drugs into cells, and if ADCs are left outside the cell, then the drug will not be released.”
It is therefore critical to ensure that the ADC releases the drug while it is still extracellular. To achieve this goal, Tagworks has designed a smart ADC that binds to cancer receptors when injected into the body, and after 1-2 days, the cells are enriched with ADCs. Robillard said: “Our innovation is that we use a second component that can ‘click release’ chemotherapy drugs from the ADC, contributing to a large number of chemotherapy drugs that release quickly and attack the tumor. This method is promising for treating a variety of cancers.”
The results of this study in mice were published recently. Robillard said: “We studied ovarian cancer and malignant colorectal cancer. In both cancers, we have observed a strong anti-cancer effect. For comparison, we also used a traditional ADC which has no effect in cancer.”
Raffaella Rossin et al, chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice, Nature Communications (2018). DOI: 10.1038/s41467-018-03880-y