Neoantigen discovery and applications in glioblastoma: An immunotherapy perspective

Abstract

Glioblastoma (GBM) is the most common and aggressive malignancy involving human brain, with a poor prognosis. Although various advanced treatment strategies have been incorporated into clinical practice, especially surgical resection, followed by radiotherapy and chemotherapy, the median patient survival is approximately 14 months. Chimeric antigen receptor (CAR) T cells have been used successfully in hematological cancers. However, CAR-T cell therapy of solid malignancies, especially GBM, is a challenge. Immune checkpoint inhibitors (ICIs), although effective in some solid tumors, are of limited use in patients with GBM. Neoantigens, which are derived from somatic mutations and expressed only on tumor cells, have led to a new approach in cancer immunotherapy. Personalized vaccine and adoptive cell therapies (ACT), the two main treatment methods targeting neoantigen, are efficacious in various cancers. Two clinical trials of personalized vaccine in GBM demonstrated immunogenicity and safety. We reviewed the development of neoantigens mainly in the field of GBM and possible therapeutic applications and challenges. In addition, organoids, which preserve the heterogeneity and molecular signatures of GBM, may play a vital role in the study of neoantigens in GBM.

Keywords: Glioblastoma organoids; Gliomas; Neoantigen peptide vaccine; Tumor immunotherapy.