Chimeric antigen receptor (CAR) T cells have been used to target tumour-specific and tumour-associated antigens in malignant gliomas. There appears to be no impediment to these cells reaching and killing target antigen-expressing tumour cells in the central nervous system (CNS). The challenge remains for these highly specific and potent agents to target antigen-negative tumour cells directly within these highly heterogeneous tumours. APC, antigen-presenting cell; DAMP, damage-associated molecular pattern; DC, dendritic cell; EGFRvIII, epidermal growth factor receptor variant III; IFNγ, interferon-γ; LN, lymph node; MHC-I, major histocompatibility complex class I; Tc, cytotoxic T cell; TCR, T cell receptor; TH, T helper cell; TNF, tumour necrosis factor. Adapted from ref.[229] (Johnson, L. A., Sanchez-Perez, L., Suryadevara, C. M. & Sampson, J. H. Chimeric antigen receptor engineered T cells can eliminate brain tumors and initiate long-term protection against recurrence. Oncoimmunology
3, e944059 (2014)), with permission of the publisher (Taylor & Francis Ltd, http://www.tandfonline.com).