Chimeric Antigen Receptor (CAR) T Cell Therapy For Solid Tumors

Projektbeschreibung

Neuartige Immuntherapie gegen solide Tumore

Immunonkologische Kuren, die eine CAR-T-Therapie beinhalten, sind wirksame Instrumente in der Krebsbehandlung. Die ungelösten Herausforderungen der CAR-T-Therapie sind die begrenzte Persistenz der Therapie und die tumorbedingte Immunsuppression. Das EU-finanzierte Projekt CAR-T-uning wird die technische und kommerzielle Durchführbarkeit einer verbesserten Behandlung mit chimären Antigenrezeptor-T-Zellen (CAR-T) mit einem neuartigen Wirkmechanismus untersuchen. Es basiert auf der jüngsten Entdeckung, dass die Hemmung des nuklearen Orphan-Rezeptors NR2F6 die Therapiepersistenz erhöht und die Immunsuppression an der Tumorstelle verringert, um die Immunantwort zu verbessern. Die Forschenden werden den neuartigen CAR-T-Ansatz anhand von In-vivo-Maus- und Ex-vivo-Patiententumormodellen validieren, wobei sie sich auf nicht-kleinzelligen Lungenkrebs konzentrieren, und die kommerzielle Durchführbarkeit bestimmen, um den besten Weg zur Marktreife zu finden.

Ziel

CAR-T(uning) will assess the technical and commercial feasibility of an improved and broadly applicable chimeric antigen receptor T-cell (CAR-T) approach based on a novel implemented mechanism of action. There is an urgent need for more effective treatment strategies against cancer, which remains the leading cause of death worldwide. Immuno-oncology regimens such as, immune checkpoint blockade therapy (ICT) and CAR-T therapy emerged as powerful tools in cancer treatment, however, in the majority of patients these fail to achieve long-lasting therapy response. Further, they remain costly and applicable to a limited range of cancer types. Specifically, CAR-T therapy faces two unresolved challenges: 1) limited therapy persistence; 2) tumor-induced immunosuppression. Consequently, no CAR-T therapy against solid tumor cancers has reached the market. Prof. Gottfried Baier has uncovered that inhibition of orphan nuclear receptor NR2F6, a downstream target of T cell antigen receptor signaling intermediate PKC, overcomes these shortcomings in a two-fold manner: 1) increased therapy persistence to improve its long-lasting effects; 2) reduced immunosuppression at the tumor site to improve immune response. Within this ERC PoC, first we will technically validate this approach using in vivo mouse and ex vivo patient-derived tumor models. We will focus on NSCLC as first indication, as it is one of the most-difficult to treat solid cancers with high mortality rate and disease burden. Subsequently, commercial feasibility will be determined by verifying IP position and strategy, performing in-depth market and competitor analyses, and finally consolidating these into a business plan to establish the best path to commercialization. Successful commercialization of CAR-T(uning) would reduce the socioeconomic burden of NSCLC, extending and improving patient lives, and enable the development of long-lasting, (cost-)effective CAR-T therapies applicable to a greater range of cancer types.