New molecule for targeted cancer treatment

Aptamers are small nucleic acid molecules that adopt three-dimensional structures and are capable of specifically recognizing target molecules.

Now, some scientists from the Bellvitge Biomedical Research Institute (IDIBELL), located in Hospitalet de Llobregat and which is one of the CERCA institutions of the Generalitat of Catalonia, in collaboration with scientists from the University of Iowa in the United States, have developed a new aptamer capable of recognizing tumor cells with great precision. This new aptamer could be used as a platform to deliver localized anticancer treatments and reduce unwanted side effects.

The research team is made up of, among others, Laura Santana-Viera and Òscar Martínez Tirado, both from IDIBELL.

The new molecule specifically recognizes the EphA2 receptor. This is a receptor that is highly expressed in a multitude of cancers such as sarcomas, breast cancer, melanoma or colorectal cancer, among others, and which, on the other hand, is very little expressed in healthy cells, which makes it a ideal candidate as a target of targeted therapy.

Dr. Òscar Martínez Tirado, head of the Sarcoma research group at IDIBELL and one of the project leaders indicates that “aptamers, unlike antibodies or other localized drug delivery platforms, can be attached to any type of therapy, be it chemotherapy or RNA cancer treatments. In addition, they can be produced on a large scale and without batch-to-batch variability.”

The project, started from scratch in the IDIBELL laboratory, has gradually successfully overcome all the steps of the design and development of the aptamer. To bring this technology to patients, Dr. Martínez Tirado has created the company Aptadel Therapeutics, focused on developing aptamers linked to cancer treatments to obtain more effective therapies with fewer adverse effects.

Research team members. (Photo: IDIBELL)

The aptamer alone already has an antitumor effect

Apart from acting as a targeted drug delivery platform, the research team found that the aptamer itself already had an antitumor effect in the tests carried out.

The target receptor to which the new molecule binds plays a very important role in the aggressiveness of tumors. The researchers found that the very binding of the aptamer reduced the metastatic capacity of cells in culture. Additionally, in a mouse model of Ewing’s Sarcoma, a bone cancer that affects children, administration of the aptamer slowed tumor growth and significantly reduced the occurrence of metastases.

“We could say that the aptamer, by itself, already has a preventive effect: it slows down the evolution of cancer”, comments Dr. Martínez Tirado. “On its own, it could help us turn cancer into a chronic disease, and at the same time, conjugated with anti-cancer drugs, it could be even more potent.”

Double selection to obtain a more affinity aptamer

The researchers have achieved this high affinity of the aptamer for the receptor thanks to an innovative double selection method that took into account both its affinity for the purified receptor and the ability of tumor cells to internalize it.

Dr. Paloma Giangrande, from the University of Iowa, points out that “this has allowed us to select the aptamers that bind more strongly to the receptor, but also the tests with cells have shown us the ones that behave best at a physiological level, those that they attached to the three-dimensional structure of the receptor and that the tumor cells could internalize”.

The study is titled “Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors”. And it has been published in the academic journal Molecular Therapy – Nucleic Acids. (Source: IDIBELL)