Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is the most common autoimmune encephalitis. Current broadly immunosuppressive treatments are often limited by side effects, necessitating the exploration of more effective and autoantibody-specific alternatives.

Our project pioneers an autologous Chimeric Autoantibody Receptor (CAAR) T-cell therapy that displays the pathogenic NMDAR epitope so that the engineered T cells can recognise and eliminate only those B-cell clones that produce anti-NMDAR antibodies, thereby providing a highly selective treatment with less side effects and better long-term prognosis. In preclinical experiments, this approach has already demonstrated potent, selective cytotoxicity in vitro and, in mouse models, eradicated antibody-expressing cells, lowered NMDAR-antibody titres in serum and brain, and showed no off-target organ toxicity. By directly removing the disease-driving B cells, this one-time cell therapy is expected to deliver faster neurological recovery with markedly fewer systemic side-effects than broad immunosuppression.

In this project, we will use a GMP-grade lentiviral vector to generate clinical-grade NMDAR-CAAR T cells on the CliniMACS Prodigy platform in the new clean-room suites of the Berlin Center for Advanced Therapies (BeCAT). These NMDAR-CAAR T cells can then be used for a planned phase I clinical trial for NMDAR encephalitis patients. Ultimately, we aim to offer patients a curative infusion that prevents relapse, minimises long-term cognitive damage and restores quality of life after NMDAR encephalitis.

Furter information here.