Recent progress in immunotherapy for malignant glioma: treatment strategies and results from clinical trials

Abstract

Background: Despite advances in surgical and adjuvant radiation therapy and chemotherapy strategies, malignant gliomas continue to be associated with poor prognoses.

Methods: We review immune-mediated treatment approaches for malignant glioma and the relevance of recent clinical trials and their outcomes. We specifically address the increasing evidence implicating the role of cytotoxic T cells in ensuring adequate immune-mediated clearance of neoplastic cells and the need for the optimization of therapies that can elicit and support such antitumor T-cell activity.

Results: The poor outcome of this disease has spurred the search for novel experimental therapies that can address and overcome the root biological phenomena associated with the lethality of this disease. The use of immunotherapy to bolster the otherwise impaired antitumor immune responses in glioma patients has received increasing attention.

Conclusions: An effective treatment paradigm for malignant gliomas may eventually require a multifaceted approach combining two or more different immunotherapeutic strategies. Such scenarios may involve the use of local cytokine gene therapy to enhance glioma-cell immunogenicity in conjunction with dendritic cell-based active vaccination to stimulate systemic tumoricidal T-cell immunity. Given the heterogeneity of this disease process and the potential risk of immunoediting out a selected, treatment-refractory tumor cell population, the concurrent use of multiple modalities that target disparate tumor characteristics may be of greatest therapeutic relevance.