An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma

David A Reardon Center for Neuro-Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA. [email protected]; Center for Neuro-Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA. [email protected]

Kai W Wucherpfennig Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA; Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA

Gordon Freeman Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA; Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA

Catherine J Wu Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA; Department of Cancer Immunology and AIDS, Dana–Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA

E Antonio Chiocca Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA; Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA

Patrick Y Wen Center for Neuro-Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA; Division of Neuro-Oncology, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA; Center for Neuro-Oncology, Dana–Farber/Brigham and Women’s Cancer Center, Boston, MA, USA; Division of Neuro-Oncology, Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA

William T Curry Jr Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

Duane A Mitchell Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA; Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA

Peter E Fecci Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA

John H Sampson Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA; Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA

Glenn Dranoff Department of Medical Oncology and Cancer Vaccine Center, Dana–Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology and Cancer Vaccine Center, Dana–Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

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Abstract

Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions.

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Financial & competing interests disclosure

JH Sampson has a consultancy, honoraria and research funding with Celldex Therapeutics. G Freeman has a consultancy with CoStim Pharmaceuticals and grants/patents/pending royalties with Bristol-Myers Squibb/Medarex, Roche/Genentech, Merck, EMD-Serono, Boehringer-Ingelheim, GlaxoSmithKline and CoStim Pharmaceuticals. DA Mitchell and JH Sampson have grants/patents/pending royalties through Celldex Therapeutics and Annias Immunotherapeutics. 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.

No writing assistance was utilized in the production of this manuscript.

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An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma

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