Optimizing CAR T cell therapy for solid tumours: a clinical perspective
Cet article décrit les principales stratégies pour améliorer les thérapies par lymphocytes CAR-T (sélection d'antigènes cibles, aphérèse précoce, fabrication rapide des lymphocytes CAR-T, lymphodéplétion, administration locorégionale, perfusions répétées), présente un cadre pour évaluer avec précision l'efficacité des thérapies CAR-T et souligne la nécessité de mettre en place des approches robustes de gestion de la toxicité afin d'atténuer les événements indésirables graves
Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the management of haematological malignancies but faces particular hurdles in the treatment of solid tumours. In this Review, we discuss important advances in refining CAR T cell therapy to provide practical clinical insights to address these challenges. We describe key strategies, including target antigen selection to enhance efficacy while minimizing on-target, off-tumour toxicities; early apheresis, rapid manufacturing and frontline application to preserve T cell fitness and ensure timely treatment; lymphodepletion to augment CAR T cell expansion; locoregional delivery to maximize local therapeutic concentrations and reduce systemic toxicity; and repeat infusions to prolong therapeutic effects. Furthermore, we discuss advanced response evaluation frameworks that will be essential for accurate assessment of the efficacy of CAR T cell therapies, and we highlight the need for robust toxicity management approaches to mitigate severe adverse events. By systematically addressing these multifaceted challenges, this Review provides a comprehensive guide for the optimization of CAR T cell therapy for solid tumours to enhance both efficacy and safety.
Nature Reviews Clinical Oncology , résumé, 2025