The critical role of the host endogenous immune compartment after intracerebroventricular CAR T cell therapy in recurrent GBM

A recent phase I trial of intracerebroventricular (ICV) bivalent CAR T cells in recurrent GBM showed promising responses, including tumor reduction and prolonged survival. However, relapse remains common.

We performed in-depth profiling of longitudinal CSF and tumor samples from responders and non-responders to characterize immune dynamics following infusion. Our study reveals that while CAR T cells activate post-infusion across all patients, outcomes were defined by divergent remodeling of the endogenous immune landscape. Cytotoxic NK cell expansion characterized responders, whereas regulatory T cell expansion and abundant baseline immunosuppressive myeloid cells characterized non-responders.