A team of researchers from the Hospital del Mar Research Institute, along with the Universitat Autònoma de Barcelona and the Universitat Pompeu Fabra, has taken a significant step in the fight against cancer by developing an innovative tool based on the genetic modification of Natural Killer (NK) cells. These cells are vital to the immune system, as they are responsible for detecting and eliminating cancerous cells. However, various tumors have found ways to evade the action of these cells, limiting the effectiveness of immunotherapy in certain cases.
The research has revealed that some types of cancer are able to secrete molecules such as TGF-β and Activin A, which suppress the function of NK cells. To counteract this tumor defense, the team has used CRISPR/Cas9 genetic editing technology to deactivate the SMAD4 gene, involved in the signaling of these inhibitory molecules. This approach not only allows NK cells to survive negative influences, but also enhances their ability to attack and destroy tumor cells.
Trials conducted in preclinical models of HER2-positive breast cancer and metastatic colorectal cancer have shown promising results; genetically modified NK cells were significantly more effective in controlling tumor growth. Dr. Aura Muntasell, a researcher at the Institute, commented that when comparing modified cells with unmodified cells, the former demonstrated a greater ability to impede tumor growth in in vivo conditions.
This project has received support from prestigious European institutions such as the Karolinska Institutet in Sweden, as well as various companies specializing in cell therapies. It has been proven that the technique can be applied to different types of NK cells, including those using chimeric antigen receptors (CAR), expanding its potential in various cancer treatments.
Dr. Clara Montagut, chief of the gastrointestinal cancer section in the Medical Oncology Department at Hospital del Mar, emphasized that modified NK cells offer new opportunities for patients with solid tumors that have been resistant to immunotherapy so far. Looking ahead, the team plans to initiate a phase I clinical trial to evaluate the safety and tolerability of these NK cells in combination with other treatments in patients with colon and rectal cancer refractory to standard therapies. This advancement represents a significant step towards enhancing immune response in the fight against solid tumors.
Referrer: MiMub in Spanish