MOTUNE-T therapy: Metabolically Optimized TUNEd T cells as treatment for recurrent glioblastoma

Glioblastoma (GB) is the most common malignant primary brain tumor in adults. Despite first-line therapy, consisting of maximal safe resection followed by concomitant radiotherapy and temozolomide chemotherapy, the
outcome remains poor with a median progression-free survival of less than 7 months1. To date, there are no treatment options to enhance the overall survival (OS) of patients with recurrent GB (rGB)2. Systemic use of nivolumab and ipilimumab, monoclonal antibodies (mAbs) blocking the immune checkpoints PD-1 and CTLA-4 respectively, showed promise in several cancer types, however they mostly failed in rGB3,4. In an effort to improve the outcome of rGB patients, our group is conducting a phase I clinical trial (GLITIPNI, NCT03233152) at UZ Brussel, combining intravenous and intracerebral delivery of immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab during surgical resection of rGB. Notably, this immune checkpoint blockade (ICB) therapy proved to be safe and resulted in a prolonged OS compared to a large historical Belgian population of rGB patients
(median OS: 38 weeks; 6, 12 & 24 month OS rate: 74%, 40% & 27% respectively)5. Still, beneficial outcome only occurred in a subset of rGB patients, implying the need for novel combination strategies for the treatment of rGB.