Ipilimumab: an investigational immunotherapy for glioblastoma

ABSTRACT

Introduction

Glioblastoma (GBM) is the most common primary malignant central nervous system tumor and has a poor overall outcome despite an aggressive standard-of-care treatment. Hence, better therapeutic modalities are necessary. Immunotherapy is a novel modality that has an indirect action against the tumor cells through activation of an anti-tumor immune response.

Areas Covered

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) belongs to a class of molecules called immune checkpoints that are inherently expressed on immune cells and lead to attenuation of the immune response. Inhibition of such molecules has been approved for the treatment of melanoma, and prolonged survival and complete responses have been reported in preclinical GBM mouse models. Ipilimumab inhibits CTLA-4 and is being investigated for the treatment of GBM, alone or in combination with other treatment modalities, in various preclinical and clinical studies, the results of the most relevant of which are discussed in this review.

Expert Opinion

Combining ipilimumab with other immunotherapy modalities and using it in specific conditions may increase the rate of objective responses in patients with GBM.

Keywords:

• CTLA-4
• immunotherapy
• immune checkpoint
• ipilimumab
• glioblastoma

(Box 1) Drug Summary Box

Article Highlights

• Immunotherapies have taken on a major role in the successful treatment of cancer. Immune checkpoint inhibitors are one important type of immunotherapy that enables the immune system to mount a significant T-cell mediated anti-cancer response in a wide range of tumors.

• Ipilimumab is a checkpoint inhibitor acting against the CTLA-4 checkpoint protein and with promise in the treatment of glioblastoma.

• While such studies revealed limited activity when using Ipilimumab as monotherapy, a key next step is the combination of Ipilimumab with other therapeutic strategies in order to maximize the therapeutic benefit in glioblastoma and to advance the development of immunotherapies in this disease. Ongoing clinical trials are highlighted, and the future perspective of Ipilimumab in glioblastoma is critically discussed.

Declaration of interest

J Dietrich is a consultant for Unum Therapeutics and is an author for UpToDate. 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. 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