Emerging immune-based technologies for high-grade gliomas

ABSTRACT

Introduction

The selection of a tailored and successful strategy for high-grade gliomas (HGGs) treatment is still a concern. The abundance of aberrant mutations within the heterogenic genetic landscape of glioblastoma strongly influences cell expansion, proliferation, and therapeutic resistance. Identification of immune evasion pathways opens the way to novel immune-based strategies. This review intends to explore the emerging immunotherapies for HGGs. The immunosuppressive mechanisms related to the tumor microenvironment and future perspectives to overcome glioma immunity barriers are also debated.

Areas covered

An extensive literature review was performed on the PubMed/Medline and ClinicalTrials.gov databases. Only highly relevant articles in English and published in the last 20 years were selected. Data about immunotherapies coming from preclinical and clinical trials were summarized.

Expert opinion

The overall level of evidence about the efficacy and safety of immunotherapies for HGGs is noteworthy. Monoclonal antibodies have been approved as second-line treatment, while peptide vaccines, viral gene strategies, and adoptive technologies proved to boost a vivid antitumor immunization. Malignant brain tumor-treating fields are ever-changing in the upcoming years. Constant refinements and development of new routes of drug administration will permit to design of novel immune-based treatment algorithms thus improving the overall survival.

KEYWORDS:

• CAR T
• glioblastoma
• high-grade glioma
• immunotherapy
• monoclonal antibodies
• oncolytic virus
• peptide vaccine
• tumor microenvironment

Article highlights

• The high-grade gliomas aggressiveness and resistance to conventional therapies are owed to the genomic heterogeneity and adaption mechanisms recognized in the tumor immunosuppressive microenvironment.

• Immunotherapies strive to manipulate and manage pathways of glioma immune escape.

• Bevacizumab, an anti-VEGF-A monoclonal antibody, is approved as a second-line treatment for recurrent glioblastoma.

• The vaccinations proved to be useful in enhancing the antitumor immune response, although not leading to an increase in survival.

• Gene therapies, based on viral vectors, or immunomodulatory gene technologies showed excellent results in vitro studies, but also in some clinical trials.

• Immunogenomics and identification of specific tumor antigens let the design of adoptive immunotherapies. The CAR T cells are engineered to selectively target glioma cells resulting in oncolysis.

• A better understanding of the resilience pathways will be vital in improving immune-based therapies for brain tumors. The future challenge is the planning of combined protocols to improve the overall and progression-free survival of HGGs patients.

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.

Additional information

Funding

This paper received no funding.