W146 - Optimized Platform for the Personalized Production of Transgenic TCR T Cells (TCR-READY)

Andrea Alonso – Immunogenetics and Immunotherapy of Autoinflammatory and Autoimmune Diseases, Fundació Recerca Clínic Barcelona – Institut d'Investigacions Biomèdiques August Pi i Sunyer; Berta Casanovas-Albertí – Fundació Recerca Clínic Barcelona – Institut d'Investigacions Biomèdiques August Pi i Sunyer; E. Azucena González-Navarro – Immunology Service, Biomedical Diagnostic Center, Hospital Clínic Barcelona; Manel Juan – Immunology Service, Biomedical Diagnostic Center, Hospital Clínic Barcelona

Abstract Text: Chronic Lymphocytic Leukemia (CLL) is the most common hematologic malignancy in adults in Western countries, with a significant increase in incidence with age. While hematologic cancer treatments have improved, especially thanks to the success of Chimeric Antigen Receptor T-cell therapy (CAR-T), its application in CLL has been limited, highlighting the need for alternative therapies.

CARs offer a therapeutic strategy designed to recognize tumor-associated antigens (TAAs) on cell surfaces. However, the dual presence of TAAs in both tumor and healthy cells poses a risk of inadvertent recognition and severe side effects. In contrast, Tumor-Specific Antigens (TSAs), specifically neoantigens arising from genomic mutations in cancer cells, offer a more specific target with lower risks. The main challenge of this strategy is the time required to identify, design, and develop neoantigen-directed cell therapies.

Our proposal aims to address this challenge by optimizing the identification of neoantigen-specific T-cell receptors (TCRs) and subsequently inducing them as transgenic TCRs (tTCRs) in T lymphocytes. The therapy will target neoantigens that can be recognized by both CD4+ and CD8+ T cells, with the former typically underutilized in cancer immunotherapies, adding additional innovative value. Sequenced TCRs specific to candidate neoantigens will serve as recognition modules, transduced into T cells using lentiviral vectors.

In summary, this project will establish an optimized platform for tTCR production, aiming to overcome the time limitation and enable the effective application of personalized TCR-based therapy to CLL patients.