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A preclinical study by the IIS Aragón demonstrates, for the first time, the viability of a CAR-T therapy aimed at myeloproliferative neoplasms (rare blood diseases with limited therapeutic options)
This study and its future clinical application have been made possible thanks to the donation of Clementa Soria and the support of the Spanish Association Against Cancer
Equipment Aragonese researchers from the IIS Aragón has demonstrated, for the first time, the feasibility of a new CAR-T cell-based immunotherapy strategy targeting a specific mutation present in some myeloproliferative neoplasms, a group of blood disorders. This work has been made possible thanks to the support of the Spanish Association Against Cancer.
The Myeloproliferative neoplasms are characterized by the abnormal production of blood cells and, in certain patient profiles, They offer limited therapeutic optionsIn some cases, these diseases are associated with mutations in the calreticulin gene, which result in an altered protein (known as mutated calreticulin or mCALR) that is only expressed in diseased cells and not in healthy ones. This characteristic makes it a highly specific target for the development of new immunotherapies.
The preclinical study has been published in the scientific journal Journal for ImmunoTherapy of Cancer, official journal of the Society for Immunotherapy of Cancer (SITC), the leading international organization dedicated to advancing cancer immunotherapy and improving clinical outcomes in cancer patients.
The investigation, with Cecilia Pesini as first author, has been led by the Doctors Ariel Ramírez Labrada and Julián Pardo, of the group Immunotherapy, Inflammation, Infection and Cancer (I3C), belonging to the IIS Aragón, the University of Zaragoza and CIBERINFEC, specializing in the development of new immunotherapeutic strategies against oncological and hematological diseases. In the work, the researchers They have designed CAR-T cells (lymphocytes modified to accurately recognize specific signals) capable of identifying and eliminating cells that express this mutation.
The results show that this immunotherapy acts selectively on diseased cells, without affecting healthy ones. This efficacy has been demonstrated in various experimental models, including cell lines, patient-derived samples, and animal models. The study also has made it possible to identify possible mechanisms that could limit the effectiveness of these types of therapies, as well as strategies to Reversing it through the combination of immunotherapy with already known drugs points to future combined therapeutic options.
The investigation has revealed with the collaboration of professionals from the Miguel Servet University Hospital and the Lozano Blesa University Clinical Hospital, as well as the Hospital Clínic of Barcelona, the ICB-CSIC and the San Jorge University, which reinforces the collaborative and multidisciplinary nature of the study.
The authors point out that These preclinical studies demonstrate the feasibility of this approach and form the basis for its translation to the clinical setting.Currently, the team is finalizing safety studies in animal models, an essential preliminary step before human trials. The results obtained to date have allowed them to design a Phase I clinical trial and make progress in preparing the necessary documentation for submission to the regulatory agency.
These CAR-T cells for the clinical trial will be produced at the Advanced Therapies Unit of the IIS Aragón “Clementa Soria”. In honor of the benefactor who made its construction possible. This will be achieved with the support of the Spanish Association Against Cancer and the Government of Aragon, whose involvement is crucial for completing the accreditation of the facility and consolidating a strategic infrastructure for the development of advanced therapies in our region, guaranteeing its full operation and sustainability. The trial will evaluate, for the first time, the safety and viability of this immunotherapy in patients. This step represents a significant advance in the search for new therapeutic options for myeloproliferative neoplasms.
