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

Descripción del proyecto

Una inmunoterapia innovadora contra los tumores sólidos

Los regímenes de inmuno-oncología que incluyen el tratamiento con linfocitos T con receptores antigénicos quiméricos (T-CAR o CAR-T, por sus siglas en inglés) son herramientas potentes en la terapia antineoplásica. La persistencia limitada de la terapia y la inmunosupresión inducida por el tumor constituyen los dos principales obstáculos no resueltos del tratamiento con linfocitos T-CAR. En el proyecto CAR-T-uning, financiado con fondos europeos, se evaluará la viabilidad técnica y comercial de un tratamiento con linfocitos T-CAR con un nuevo mecanismo de acción. Este se basa en el descubrimiento reciente de que la inhibición del receptor nuclear huérfano NR2F6 aumenta la persistencia de la terapia y reduce la inmunosupresión en el lugar del tumor para mejorar la respuesta inmunitaria. Los investigadores validarán el nuevo tratamiento con linfocitos T-CAR con modelos tumorales derivados de pacientes «ex vivo» y ratones «in vivo», centrándose en los carcinomas broncopulmonares no microcíticos, y determinarán la viabilidad comercial para establecer el mejor camino hacia el mercado.

Objetivo

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.