Current Status and Challenges of Vaccination Therapy for Glioblastoma

Abstract

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and deadly type of central nervous system malignancy in adults. Despite significant breakthroughs in current GBM treatments such as surgery, radiotherapy, and chemotherapy, the prognosis for late-stage glioblastoma remains bleak due to tumor recurrence following surgical resection. The poor prognosis highlights the evident and pressing need for more efficient and targeted treatment. Vaccination has successfully treated patients with advanced colorectal and lung cancer. Therefore, the potential value of using tumor vaccines in treating glioblastoma is increasingly discussed as a monotherapy or in combination with other cellular immunotherapies. Cancer vaccination includes both passive administration of monoclonal antibodies and active vaccination procedures to activate, boost, or bias antitumor immunity against cancer cells. This article focuses on active immunotherapy with peptide, genetic (DNA, mRNA), and cell-based vaccines in treating GBM and reviews the various treatment approaches currently being tested. Although the ease of synthesis, relative safety, and ability to elicit tumor-specific immune responses have made these vaccines an invaluable tool for cancer treatment, more extensive cohort studies and better guidelines are needed to improve the efficacy of these vaccines in anti-GBM therapy.

Fig 1:. Current vaccination therapy status for glioblastoma.

Glioblastoma (GBM) vaccination treatment have been relied on GBM-specific antigens presentation by dendritic cells (DCs) and T cell activation by different types of peptides. Cytotoxic T cells mediated immunosuppression can be carried out by recruiting several immune-checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte protein 4 (CTLA-4) antibodies (or other inhibitors). Another way for cancer treatment relied on genetically engineered chimeric antigen receptor (CAR) T cells and oncolytic viral treatment to medicate cancer cell lysis and promote tumor necrosis. MHC II, Major histocompatibility complex 2; TCR, T-cell receptor; EGFRvIII, Epidermal growth factor receptor variant III.