T cells genetically modified to express chimeric antigen receptors (CARs) constitute advanced therapy medicinal products developed for cancer treatment. CARs present one extracellular domain based on the single-chain variable fragment (scFv) from a monoclonal antibody, a transmembrane region and an intracellular domain that varies depending on CAR generation and mediate its function. CARs mediate tumor elimination without the need for HLA recognition.

CAR T cell-based immunotherapy constitute a new option for the treatment of different type of tumors. As in other gene therapies, one of the main limitations associated to lentiviral-mediated CAR T cell therapies is the high cost associated to the manufacturing of viral vectors. At the HIT Division of CIEMAT, and in close collaboration with Centro de Investigación Médica Aplicada (CIMA) and Clínica Universitaria de Navarra (CUN), we have developed a protocol to generate CAR-T cells using transposons, a viral-free method which should significantly reduce the cost of these kind of treatments. We are also collaborating with other National and European teams to generate an allogenic CAR-T immunotherapy using transposons and the latest gene editing tools to universalize these treatments.

A different research line of CAR T immunotherapy of our Division is focused on the treatment of head and neck squamous cell carcinoma (HNSCC). This tumor is present in a high proportion of patients with Fanconi Anemia (FA). Because of the high toxicity of radio and chemotherapy in FA patients, we have considered that CAR T cell therapies should constitute a much less toxic therapy for HNSCC in FA patients. Our current preclinical studies aim to demonstrate the efficacy and safety in preclinical models of FA HNSCCs with the purpose of proposing a clinical trial in FA patients.

 

Members

Juan A. Bueren Roncero. Professor

José Antonio Casado Olea. PhD 

Rosa M. Yáñez González. PhD

Begoña Díez Cabezas. PhD

María Fernández García. PhD

Andrea López Arranz. PhD Student

Paula Vela Cristóbal. Technician

 

Juan A. Bueren Roncero

Juan A. Bueren Roncero

Head of Research Area