Promising vaccines for treating glioblastoma

ABSTRACT

Introduction: Conventional therapies for glioblastoma  (GBM) typically fail to provide lasting antitumor benefits, owing to their inability to specifically eliminate all malignant cells. Cancer vaccines are currently being evaluated as a means to direct the adaptive immune system to target residual GBM cells that remain following standard-of-care treatment.

Areas covered: In this review, we provide an overview of the more noteworthy cancer vaccines that are under investigation for the treatment of GBM, as well as potential future directions that may enhance GBM-vaccine effectiveness.

Expert opinion: To date, no cancer vaccines have been proven effective against GBM; however, only a few have reached phase III clinical testing. Clinical immunological monitoring data suggest that GBM vaccines are capable of stimulating immune responses reactive to GBM antigens, but whether these responses have an appreciable antitumor effect on GBM is still uncertain. Nevertheless, there have been several promising outcomes in early phase clinical trials, which lend encouragement to this area of study. Further studies with GBM vaccines are, therefore, warranted.

KEYWORDS:

• Glioblastoma
• GBM
• vaccine
• immunotherapy
• immunogenic
• oncolytic

Article highlights

• The current standard-of-care regimen for glioblastoma using resection, radiotherapy, and temozolomide chemotherapy does little to prolong survival due to its inability to effectively eradicate all malignant cells.

• The profound cytotoxic potential and molecular-guided precision of immune cells make immunotherapy a promising approach to treat this highly infiltrative disease.

• Given the intertumoral heterogeneity of glioblastoma, cancer vaccines, which attempt to stimulate an endogenous immune response to tumor antigens, represent a viable means to tailor immunotherapy on a patient-by-patient basis.

• Various cancer vaccine platforms have demonstrated efficacy in preclinical models of malignant glioma and several have made their way into clinical trials for the treatment of glioblastoma.

• Intratumoral antigenic heterogeneity represents a significant obstacle for GBM vaccines, as monovalent vaccines targeting subclonal antigens result in the outgrowth of antigen-loss variants/antigen escape. Therefore, vaccines that target a broader repertoire of tumor cells are needed.

• At the current time, proof of cancer vaccine efficacy has not been demonstrated for glioblastoma; however, several encouraging pursuits are underway.

This box summarizes key points contained in the article.

Declaration of interest

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other 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 apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

L Sanchez-Perez is funded by the NIH.