Emerging immunotherapies for glioblastoma.

Journal Article (Review)

Immunotherapy for brain cancer has evolved dramatically over the past decade, owed in part to our improved understanding of how the immune system interacts with tumors residing within the central nervous system (CNS). Glioblastoma (GBM), the most common primary malignant brain tumor in adults, carries a poor prognosis (<15 months) and only few advances have been made since the FDA's approval of temozolomide (TMZ) in 2005. Importantly, several immunotherapies have now entered patient trials based on promising preclinical data, and recent studies have shed light on how GBM employs a slew of immunosuppressive mechanisms that may be targeted for therapeutic gain. Altogether, accumulating evidence suggests immunotherapy may soon earn its keep as a mainstay of clinical management for GBM.Here, we review cancer vaccines, checkpoint inhibitors, adoptive T-cell immunotherapy, and oncolytic virotherapy.Checkpoint blockade induces antitumor activity by preventing negative regulation of T-cell activation. This platform, however, depends on an existing frequency of tumor-reactive T cells. GBM tumors are exceptionally equipped to prevent this, occupying low levels of antigen expression and elaborate mechanisms of immunosuppression. Therefore, checkpoint blockade may be most effective when used in combination with a DC vaccine or adoptively transferred tumor-specific T cells generated ex vivo. Both approaches have been shown to induce endogenous immune responses against tumor antigens, providing a rationale for use with checkpoint blockade where both primary and secondary responses may be potentiated.

Full Text

Duke Authors

Cited Authors

  • Desai, R; Suryadevara, CM; Batich, KA; Farber, SH; Sanchez-Perez, L; Sampson, JH

Published Date

  • June 2016

Published In

Volume / Issue

  • 21 / 2

Start / End Page

  • 133 - 145

PubMed ID

  • 27223671

Electronic International Standard Serial Number (EISSN)

  • 1744-7623

International Standard Serial Number (ISSN)

  • 1472-8214

Digital Object Identifier (DOI)

  • 10.1080/14728214.2016.1186643

Language

  • eng