Optimisation de l’efficacité et de la sécurité d’utilisation des lymphocytes CAR-T

Optimizing efficacy and security of CAR-T cells, and immune monitoring

¹ AP-HP, service d’oncologie et d’hématologie pédiatrique, Hôpital A. Trousseau, Paris, France
² Institut Curie, PSL University, Inserm U932, Immunité et cancer, Paris, France
³ Laboratoire d’immunologie clinique et d’ immunomonitoring, Institut Curie, Paris, France
⁴ CellAction, Institut Curie, Suresnes, France

^* cecile.alanio@curie.fr

Résumé

Le système immunitaire joue un rôle déterminant dans le contrôle et l’éradication des tumeurs. Une meilleure compréhension des mécanismes en jeu a permis le développement des immunothérapies, et notamment des thérapies par lymphocytes CAR-T. Ces thérapies ont montré une grande efficacité dans les maladies hématologiques, mais leur application aux tumeurs solides nécessite des optimisations pour améliorer leur efficacité et leur sécurité. Ces ajustements permettront une plus grande applicabilité des lymphocytes CAR-T, non seulement pour les traitements anti-tumoraux mais aussi pour le traitement de maladies auto-immunes ou fibreuses.

Abstract

The immune system plays a critical role in the control and eradication of tumors. A better understanding of the anti-tumor immune mechanisms over the last decade has led to the development of immunotherapies, including cellular therapies such as those using CAR-T cells. These therapies have been remarkably effective in hematological malignancies. However, their application to solid tumors requires some optimization. Many efforts are being made in this regard, both to increase the efficacy of CAR-T cells, and to make them more secure. For the former goal, there is a need for the identification of new targets, better activation strategies, or arming T cells in a way that makes them able to overcome intra-tumoral barriers. For the latter goal, dose adjustment, locoregional administration or use of suicide genes are currently investigated as ways to mitigate the risks of this therapy. Together, these adjustments will permit larger applicability of CAR-T cells, in anti-tumor immunity, but also in the context of auto-immune diseases or fibrolytic therapies.