Follicular lymphoma is one of the most common types of lymphoma. Although most patients respond to initial treatment, and CD19-directed CAR-T therapies have significantly improved the prognosis for more advanced cases, some patients ultimately relapse, with few therapeutic options available to them.
CD70, a new biomarker to identify patients at higher risk of relapse
To understand the mechanisms associated with these relapses, the research team analysed tumour samples obtained at the time of diagnosis from patients with a long clinical follow-up. The genetic and tumour microenvironment study revealed that patients who subsequently relapsed presented elevated expression of the CD70 protein both in tumour cells and in certain populations of immune cells surrounding the tumour. This characteristic was associated with shorter progression-free survival.
“The identification of CD70 at the time of diagnosis allows us to distinguish those people with a higher risk of relapse before the disease progresses. In the future, this biomarker could help to better stratify patients and adapt their therapeutic strategies according to their risk, moving towards a more personalised medicine in follicular lymphoma", explains Patricia Pérez-Galán, head of the research group on Microenvironment in lymphoma pathogenesis and therapy at IDIBAPS, researcher at the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) and co-leader of the study.
A dual-target CAR-T therapy improves tumour control in preclinical models
Based on this discovery, the team proposed a new therapeutic strategy: to convert ARI-0001, the academic CAR-T against CD19 developed at the institution and approved for clinical use under the hospital exemption, into a dual CAR-T therapy by incorporating a second CAR directed against CD70. This new dual CAR-T was evaluated in patient-derived tumoroids and in animal models. The results showed higher antitumour activity than that of conventional CAR-T directed only against CD19, with better elimination of tumour cells and more effective control of the disease.
“Our results demonstrate that the CD19-CD70 dual target is a viable strategy with great therapeutic potential. In preclinical models, the new CAR-T therapy has achieved better tumour control and has reduced the resistance mechanisms associated with relapses", says Sònia Guedan, head of the research group on Cellular immunotherapies for cancer at IDIBAPS and co-leader of the project.
Towards the clinical evaluation of a new generation of CAR-T
Beyond follicular lymphoma, the research team points out that this strategy could benefit patients with other aggressive lymphomas, such as mantle cell lymphoma and diffuse large B-cell lymphoma. In these diseases there has also been description of relapses associated with reduced expression of CD19, a resistance mechanism that the CD19-CD70 dual target could help overcome. Ferran Araujo-Ayala and Maria Ros, both researchers at IDIBAPS and co-authors of the work, assert that the preliminary results in preclinical models of these neoplasms are promising.
The results obtained open the door to the clinical development of this new therapy. The next steps include completing the safety studies, optimizing the manufacture, and preparing the regulatory dossier to enable application for the authorisation of a clinical trial.
This project has been possible thanks to La Marató de 3Cat which has funded the identification of CD70 as a prognostic biomarker. And also, thanks to the Follicular Lymphoma Foundation, which has funded the generation of the dual CAR-T. In addition, the collaboration with Carlos E. de Andrea, from the Clínica Universidad de Navarra-CUN, has been fundamental for the validation of the results at the protein level.
Reference article
CD70 Overexpression at Diagnosis Predicts Relapse and Supports Dual CD19-CD70 CAR-T Therapy in Follicular Lymphoma. Ferran Araujo-Ayala et al. Blood. 2026. https://doi.org/10.1182/blood.2025032663
