CAR T-cell therapy for glioblastoma: ready for the next round of clinical testing?

ABSTRACT

Introduction: The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptors (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics.

Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function.

Expert commentary: While preclinical studies have highlighted the potent anti-GBM activity of CAR T cells, the initial foray of CAR T-cell therapies into the clinic resulted only in limited benefits for GBM patients. Additional genetic modification of CAR T cells has resulted in a significant increase in their anti-GBM activity in preclinical models. We are optimistic that clinical testing of these enhanced CAR T cells will be safe and result in improved anti-glioma activity in GBM patients.

KEYWORDS:

• Glioblastoma
• immunotherapy
• T cells
• gene therapy
• chimeric antigen receptor
• tumor microenvironment

Declaration of interest

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

Additional information

Funding

The authors report receiving financial support of their preclinical and clinical GBM studies by the American Brain Tumor Association Basic Research Fellowship in honor of Joel A. Gingras, Jr. (BRF160004), Alex's Lemonade Stand Foundation (ALSF), National Institute of Health grant CA203270, and the James S. McDonnell Foundation (JSMF) and Cancer Prevention and Research Institute of Texas grant RP110553.