Atim-32. phase iia clinical trial evaluating dendritic cell vaccine for the treatment of low-grade gliomas

We conducted an exploratory phase IIa clinical trial to evaluate the safety and efficacy of autologous tumor lysate-pulsed dendritic cell vaccine therapy in patients with low grade gliomas. Five patients, three with newly-diagnosed and two with recurrent grade II gliomas, enrolled and each received at least one injection of the vaccine. The treatment was well-tolerated with only mild side effects such as headache, myalgia and fatigue. There were no grade 3 or 4 adverse events. Interestingly, the patient with the longest progression-free survival, almost 43 months, was 85 years of age at the time of surgery with a diagnosis of IDH1-wildtype 1p/19q-intact astrocytoma, the most aggressive pathology in the trial. The patient whose tumor has not yet progressed, with a TTP >27 months to date, was one of the recurrent tumors at the time of vaccine. Antibody responses to IDH1 R132H mutation, a known neoantigen present in 4/5 tumors, were measured and found to be present in all four patients with IDH mutant tumors by ELISA. We analyzed pre- and post-vaccine tumor specimens of two patients and found significant increases of CD8+ PD-1+ tumor-infiltrating lymphocytes (TILs), but no significant increase of PD-L1 expression in the tumor cells themselves. There was no significant difference in time to progression for the patients in this clinical trial compared control patients who were matched for tumor grade, type, recurrence number, IDH1 status and 1p/19q status. Such findings indicate that further research is warranted to understand why certain low-grade tumors respond better to the vaccine than others. There was also evidence of a PD-1+ cytotoxic T-cell infiltration induced by the vaccine that may benefit from combined PD-1 blockade therapy.