Ignacio Melero
Professor of Immunology at the University of Navarra, CIMA researcher and co-director of the Department of Immunology and Immunotherapy at the Clínica Universidad de Navarra.
It is a clinical trial led by Dr. Carl June with extraordinary results of efficacy in patients with lymphoma previously refractory to CAR immunotherapy in which more than half of the previously refractory patients achieve a complete response of their lymphoma.
The molecular trick consists of introducing into the lymphocytes, together with the CAR gene, another gene coding for an immunostimulant substance called interleukin-18. The CARs thus constructed to co-express cytokines are called armed CARs, and have greater therapeutic potency. This concept has been tested preclinically and clinically with other cytokines, but with more modest clinical results. Our group published in preclinical models the mechanisms by which we observed that adoptive cell therapy armed with interleukin-18 is more potent through the lymphocytes' own self-stimulation, which allows them to better migrate to tumor tissue and adapt to the metabolic stress present there.
The observations in patient samples of persistence of CARs demonstrating interleukin-18 activity are extraordinarily interesting. From a safety standpoint, adverse effects are very comparable to those of conventional CAR therapy and appear manageable. This strategy seems suitable for treating refractory patients and all indications are that it will soon be tested as the first CAR treatment in patients with B lymphomas refractory to conventional therapies.