Abstract
The use of immunotherapies for the treatment of brain tumors is a topic that has garnered considerable excitement in recent years. Discoveries such as the presence of a glymphatic system and immune surveillance in the central nervous system (CNS) have shattered the theory of immune privilege and opened up the possibility of treating CNS malignancies with immunotherapies. However, despite many immunotherapy clinical trials aimed at treating glioblastoma (GBM), very few have demonstrated a significant survival benefit. Several factors for this have been identified, one of which is that GBMs are immunologically “cold,” implying that the cancer does not induce a strong T cell response. It is postulated that this is why clinical trials using an immune checkpoint inhibitor alone have not demonstrated efficacy. While it is well established that anti-cancer T cell responses can be facilitated by the presentation of tumor-specific antigens to the immune system, treatment-related death of GBM cells and subsequent release of molecules have not been shown to be sufficient to evoke an anti-tumor immune response effective enough to have a significant impact. To overcome this limitation, vaccines can be used to introduce exogenous antigens at higher concentrations to the immune system to induce strong tumor antigen-specific T cell responses. In this review, we will describe vaccination strategies that are under investigation to treat GBM; categorizing them based on their target antigens, form of antigens, vehicles used, and pairing with specific adjuvants. We will review the concept of vaccine therapy in combination with immune checkpoint inhibitors, as it is hypothesized that this approach may be more effective in overcoming the immunosuppressive milieu of GBM. Clinical trial design and the need for incorporating robust immune monitoring into future studies will also be discussed here. We believe that the integration of evolving technologies of vaccine development, delivery, and immune monitoring will further enhance the role of these therapies and will likely remain an important area of investigation for future treatment strategies for GBM patients.
Highlights
Glioblastoma (GBM) is one of the most lethal primary brain malignancies, with a median overall survival of 14-17 months despite intervention with both surgery and chemo-radiation therapy [1, 2]
Some of the most promising vaccines that are currently under investigation for the treatment of GBM were discussed including the rationale for their use and the clinical trial results far
This review serves as a guide or provides an outline for investigators and clinicians as they seek to design and implement different vaccine-based approaches to treat patients suffering from GBM
Summary
Glioblastoma (GBM) is one of the most lethal primary brain malignancies, with a median overall survival of 14-17 months despite intervention with both surgery and chemo-radiation therapy [1, 2]. The first (NCT02287428) study is using a vaccine strategy that targets 20 mutant peptides directly expressed on the patient’s tumor [19, 25] in combination with pembrolizumab (anti-PD-1 antibody) and radiation therapy in newly diagnosed patients with MGMT-unmethylated GBM [25].
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