Scientists at the University of Göttingen develop drug for antibody tumour therapy
Chemists at the University of Göttingen have developed new cytotoxic drugs which could revolutionise antibody-based tumour therapy approaches. The research team succeeded in modifying the natural product Duocarmycin into “prodrug” formats – which means that it only develops its effect once inside the tumour cell, thus reducing the likelihood of potential side effects on passage through the body. The University has entered into an exclusive licence agreement with the biotechnology company Iksuda Therapeutics for onward development and commercialisation in cancer therapeutics.
Antibody tumour therapies have enabled significant therapeutic benefits to patients suffering from cancer, autoimmune diseases and other serious diseases. However, many antibodies lack sufficient anti-tumour activity in the cell. This can be achieved by the use of antibody-drug conjugates (ADCs), where antibodies, which target specific cancer antigens, are armed with powerful cell-killing (cytotoxic) agents or ‘payloads’. ADCs have become powerful additions to the cancer treatment armoury, with several recent drug approvals and expanding clinical validation. However, most early-wave ADCs are associated with poor tolerability profiles, often due to a reduction in efficacy caused by the loss of the toxic payload whilst in circulation. Some programmes have failed as a result of low efficacy, where the payload is not active enough once inside the cell. ADC innovators, such as Iksuda, are working on the development of ADCs with a higher therapeutic index and finding safer ways to deliver potent cell-killing toxins. Iksuda has developed their own stable conjugation platform which reduces the risk of loss of efficacy.
One way to enhance both safety and efficacy of an ADC is to ensure that the payload is only released via tumour-activated mechanisms. With this approach, the precursors, called prodrugs, are able to release more potent payloads inside the cancer cell, with limited impact outside the cell.