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Seed Funding Program 2022

T-SIRE

T cell receptor discovery in brain metastases

Coordinators

Lukas Bunse

Neurological Clinic, UMM

dkfz.de

Stefan Eichmüller

GMP & T Cell Therapy, DKFZ

Detailed description

Brain metastases occur in up to 40% of cancer patients with increasing incidence. Thus far, immune checkpoint inhibitors show promising results only in some subtypes of asymptomatic brain metastases. Conversely, cellular immunotherapy has been demonstrated to be effective in eradicating some cancers, but is still greatly hurdled by the limited number of suitable cell surface antigens that can be targeted by chimeric antigen receptor T cell therapy (CAR-T).  In contrast to CAR-T, T cell receptor therapy (TCR-T) enables targeting of intracellular, mostly tumor-specific antigens.  T-SIRE aims at personalized high-speed and precise brain tumor-reactive T cell receptor (TCR) discovery for immediate therapeutic use. Patient autologous brain tumor-reactive T cells will be specifically and efficiently expanded from the tumor microenvironment on a state-of-the-art high throughput optofluidic technology platform and then characterized by single cell TCR sequencing and functionally validated. Conceptually, T-SIRE enables new treatment options for patients with brain metastases by high-throughput optofluidic guided T cell selection and TCR cloning.