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Neoantigen discovery and applications in glioblastoma: An immunotherapy perspective
Chen Wang1, Mingchen Yu2, Wei Zhang3
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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.
Insights
Glioblastoma (GBM) treatment remains challenging. Neoantigen-targeted therapies, including personalized vaccines and adoptive cell therapies (ACT), show promise for GBM, with organoids aiding research.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Genomics
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis despite standard treatments.
- Current therapies like surgery, radiotherapy, and chemotherapy offer limited survival benefits (median ~14 months).
- CAR-T cell therapy and immune checkpoint inhibitors (ICIs) show limited efficacy in GBM.
Purpose of the Study:
- To review the development of neoantigens for Glioblastoma (GBM) treatment.
- To explore potential therapeutic applications and challenges of neoantigen-based immunotherapies for GBM.
- To highlight the role of organoids in studying GBM neoantigens.
Main Methods:
- Literature review focusing on neoantigen discovery and therapeutic strategies in GBM.
- Analysis of clinical trial data for personalized vaccines and adoptive cell therapies (ACT) in GBM.
- Discussion of GBM organoid models for neoantigen research.
Main Results:
- Neoantigens, arising from somatic mutations, offer a novel approach to cancer immunotherapy.
- Personalized vaccines targeting neoantigens have demonstrated immunogenicity and safety in GBM clinical trials.
- Adoptive cell therapies (ACT) targeting neoantigens are effective in various cancers and hold potential for GBM.
Conclusions:
- Neoantigen-based therapies, including personalized vaccines and ACT, represent a promising frontier for Glioblastoma treatment.
- Overcoming challenges in CAR-T cell therapy and ICI efficacy for GBM is crucial.
- GBM organoids are valuable tools for advancing neoantigen research and developing effective immunotherapies.
