medwireNews: Treatment with autologous chimeric antigen receptor (CAR) T cells directed against the epidermal growth factor receptor variant III (EGFRvIII) mutation is feasible and well tolerated in patients with recurrent glioblastoma, indicates a first-in-human study. But barriers to the clinical efficacy of the therapy exist, says the research team, including the inhibitory tumor microenvironment, which becomes even more immunosuppressive after CAR T cells. Lead author Marcela Maus (Massachusetts General Hospital, Boston, USA) and colleagues chose the EGFRvIII mutation as it is a tumor-specific, oncogenic, and immunogenic epitope expressed in around 30% of newly diagnosed cases of glioblastoma. In this phase I study, reported in Science Translational Medicine, 10 patients with EGFRvIII-expressing glioblastoma that had progressed after at least one prior line of therapy were given a single infusion of an autologous EGFRvIII-directed CAR T product within a week of progression. There were no dose-limiting toxicities, and no evidence of off-target EGFR-directed effects such as rash, diarrhea, or pulmonary symptoms or systemic cytokine release syndrome. Neurologic events were observed in three patients and included a seizure at day 9 in one patient and neurologic decline in two patients, at day 15 in one case and postoperatively in the other. Although such … Continue reading
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