Aptamers are small nucleic acid molecules that adopt three-dimensional structures and can specifically recognize target molecules. Now, a research team from the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Iowa 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 new molecule presented in the scientific journal Molecular Therapy – Nucleic Acids recognizes the EphA2 receptor. This receptor is highly expressed in a lot of cancers such as sarcomas, breast cancer, melanoma, or colorectal cancer, among others. Also, its expression in healthy cells is really low, which makes it an ideal candidate as a target of localized therapy.
Dr. Òscar Martínez Tirado, head of the Sarcomes research group at IDIBELL and one of the project leaders, indicates that “aptamers, unlike antibodies or other localized drug delivery platforms, can be linked to any type of therapy, like chemotherapy or RNA therapy, and they can be large-scale produced and without batch-to-batch variability.”
The project started from scratch in the IDIBELL laboratory and it has gradually successfully overcome all the steps of the aptamer design and development. To bring this technology to patients, Dr. Martínez Tirado has created Aptadel Therapeutics, focused on developing aptamers linked to cancer treatments to obtain more effective therapies with fewer adverse effects.
Aptamer alone already has an antitumor effect
Apart from acting as a targeted drug delivery platform, the research team found that the aptamer alone already had an antitumor effect.
The target receptor, to which the new molecule binds, plays a very important role in tumor aggressiveness. The researchers found that the aptamer binding reduce metastatic capacity of cells in culture. Additionally, in a mouse model of Ewing’s Sarcoma, a bone cancer that affects children, aptamer administration slowed tumor growth and significantly reduced the occurrence of metastases.
“We could say that aptamer alone already has a preventive effect, it slows down the evolution of cancer -says Dr. Martínez Tirado-. Alone, 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 powerful.”
Double selection to obtain a more affinity aptamer
The researchers have achieved this high-affinity aptamer thanks to an innovative double-selection method that considered 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, cell assays have shown us the ones that act at physiological level, those that attached to the three-dimensional structure of the receptor and that the tumor cells could internalize”.
All this has been possible thanks to the support of the Alba Pérez Foundation, the Ministry of Science and Innovation, and the grants of the Spanish Association Against Cancer Ideas Semilla AECC and AECC Innova.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).