Immunotherapy for Glioblastoma: Adoptive T-cell Strategies

Abstract

Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immunotherapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CAR), represents a particularly promising approach. Despite the recent success of CAR T cells for blood cancers, the question remains whether this powerful anticancer therapy will ultimately work for brain tumors, and whether the primary immunologic challenges in this disease, which include antigenic heterogeneity, immune suppression, and T-cell exhaustion, can be adequately addressed. Here, we contextualize these concepts by reviewing recent developments in ACT for GBM, with a special focus on pioneering clinical trials of CAR T-cell therapy.

Figure 1.

Chimeric antigen receptors are composed of an extracellular antigen-binding domain, typically in the form of an antibody-derived single-chain variable fragment (scFv), translated in tandem with assorted intracellular signaling regions that have differential effects on T-cell proliferation, effector function and survival.