Researchers have developed a novel approach to target and kill cancer cells. The study, published in the Journal of the American Chemical Society, details the development of hairpin-shaped DNA molecules that can selectively induce a potent immune response in cancer cells.
New drugs with a new mechanism of action
Cancer is one of the biggest global health concerns. Current treatment approaches have various limitations. Recently, nucleic acids (like RNA and DNA) have been explored as cancer immunotherapeutic materials. This is because RNA and DNA molecules are recognised by sensors that are on the surface of cells and inside cells. This triggers a potent innate immune response that kills the cells.
Researchers at the University of Tokyo have chemically synthesised a pair of hairpin-shaped DNA molecules that can target and kill cancer cells that overexpress a particular microRNA molecule.
Akimitsu Okamoto, Professor at the Graduate School of Engineering in University of Tokyo said, “We thought that if we can create new drugs that work by a different mechanism of action from that of conventional drugs, they may be effective against cancers that have been untreatable up to now.”
Hairpin-shaped DNA molecules activate the innate immune response
The researchers developed a DNA-based anti-cancer drug that could differentiate between cancer cells and healthy cells. This meant that the immune response was not activated in healthy cells, which prevented inadvertent immunotoxicity.
The researchers achieved selective immune activation in cancer cells. This is because some cancer cells overexpress microRNA-21. The hairpin DNA pairs interacted with the microRNA-21, unravelled and joined together (figure 1). This formed longer chains of DNA. The immune system was then able to recognise the microRNA-21 as dangerous. This led to a potent innate immune response which killed the cancer cells.
The DNA hairpins were effective against cells from human-derived cervical cancer and breast cancer and mouse-derived malignant melanomas. These cells overexpressed microRNA-21.
A new class of cancer immunotherapies
The study was the first to show that the assembly of intracellular DNA can cause cancer cells to die in a selective manner. The researchers hope that this will introduce a blueprint for a class of nucleic acid-based drug candidates that have not been explored as cancer therapies before.
Professor Okamoto said, “The results of this study are good news for doctors, drug discovery researchers and cancer patients, as we believe it will give them new options for drug development and medication policies. Next, we will aim for drug discovery based on the results of this research, and examine in detail the drug efficacy, toxicity and potential administration methods.”