Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase I trial [RNA-seq]

Glioblastoma is a devastating disease with a prognosis of less than 24 months. Recent studies have shown encouraging results using neoantigen-based vaccines to stimulate glioblastoma-directed immune responses, but overall immunogenicity has been low. Here, we report the results of a phase 1 clinical trial (NCT04015700) to assess the safety and efficacy of GNOS-PV01, a personalized DNA vaccine platform, in patients with newly diagnosed MGMT unmethylated glioblastoma following surgery and radiation. Results show GNOS-PV01 is able to safely immunize against up to 40 neoantigens per patient (range 17-40) with neoantigen-specific T cell responses detectable in all evaluated subjects post-vaccination (7 of 7). Furthermore, we developed a novel T cell enrichment method for single nuclei RNA-sequencing to transcriptionally characterize tumor-infiltrating T cells after vaccination. Survival outcomes were encouraging with one-third of vaccinated patients (3 of 9) alive beyond 24 months. Moreover, induction of neoantigen-specific responses was associated with subsequent reactivity to PD-1 blockade therapy. Overall design: We performed bulk RNA-sequencing on multiple tumor regions from nine patients.