https://orcid.org/0000-0002-2824-4926
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ABSTRACT
Introduction
Gliomas are infiltrating brain tumors associated with high morbidity and mortality. Current standard of care includes radiation, chemotherapy, and surgical resection. Today, survival rates for malignant glioma patients remain dismal and unchanged for decades. The glioma microenvironment is highly immunosuppressive and consequently this has motivated the development of immunotherapies for counteracting this condition, enabling the immune cells within the tumor microenvironment to react against this tumor.
Areas covered
The authors discuss immunotherapeutic strategies for glioma in phase-I/II clinical trials and illuminate their mechanisms of action, limitations, and key challenges. They also examine promising approaches under preclinical development.
Expert opinion
In the last decade there has been an expansion in immune-mediated anti-cancer therapies. In the glioma field, sophisticated strategies have been successfully implemented in preclinical models. Unfortunately, clinical trials have not yet yielded consistent results for glioma patients. This could be attributed to our limited understanding of the complex immune cell infiltration and its interaction with the tumor cells, the selected time for treatment, the combination with other therapies and the route of administration of the agent. Applying these modalities to treat malignant glioma is challenging, but many new alternatives are emerging to by-pass these hurdles.
Abbreviations
| BBB | = | Blood-Brain Barrier |
| CAR | = | Chimeric Antigen Receptor |
| CNS | = | Central Nervous System |
| CCNU | = | Lomustine |
| CT | = | Combination Therapy |
| DC | = | Dendritic Cell |
| DCV | = | Dendritic Cell Vaccines |
| DMG | = | Diffuse Midline Glioma |
| FDA | = | Food And Drug Administration |
| GBM | = | Glioblastoma |
| HMGB1 | = | High Mobility Group Box 1 |
| i.v. | = | Intravenously |
| IDO1 | = | Indoleamine 2,3-Dioxygenase 1 |
| MS | = | Median Survival |
| NPs | = | Nanoparticles |
| OS | = | Overall Survival |
| OV | = | Oncolytic Virus |
| PFS | = | Progression Free Survival |
| rGBM | = | Recurrent Glioblastoma |
| SOC | = | Standard Of Care |
| TAA | = | Tumor-Associated Antigen |
| TCR | = | T-Cell Receptor |
| TME | = | Tumor Microenvironment |
| TMZ | = | Temozolomide |
| TSA | = | Tumor-Specific Antigen |
| TT-RNA | = | Total Tumor RNA |
| VDX | = | Veledimexin |
| VEGF | = | Vascular Endothelial Growth Factor |
Article highlights
Malignant gliomas or HGG are the most frequent tumors of the central nervous system. Even though there has been advances in their diagnosis and treatment strategies, HGG have dismal prognosis and currently remain incurable.
It has been demonstrated that HGG displays an immunosuppressive tumor microenvironment, involving the recruitment of immunomodulatory cells and the secretion of immunomodulatory cytokines.
In the last years, there has been an expansion in the immunotherapeutic strategies designed to treat different types of cancers, and many of these are currently approved to be used in the clinic due to their significant improvement in patient survival.
Treating glioma with an immunotherapeutic approach can be challenging due to their anatomic location, the intrinsic immunosuppressive microenvironment, and the tumor heterogeneity. However, several therapies under pre-clinical and clinical study were developed to beat these hurdles. Also, the development of new alternatives for drug delivery, such as nanoparticles, have yielded encouraging results in preclinical models.
The development of immunotherapies against glioma is promising since pre-clinical studies in diverse immunotherapies demonstrated encouraging biological effects. However, favorable and long-lasting clinical responses remain to be seen.
This box summarizes the key points contained in the article.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.