Despite extensive preclinical research on immunotherapeutic approaches,
malignant glioma remains a devastating disease of the central nervous system for which standard of care treatment is still confined to resection and
radiochemotherapy. For peripheral solid
tumors,
immune checkpoint inhibition has shown substantial clinical benefit, while promising preclinical results have yet failed to translate into clinical efficacy for
brain tumor patients. With the advent of high-throughput sequencing technologies,
tumor antigens and corresponding
T cell receptors (TCR) and
antibodies have been identified, leading to the development of
chimeric antigen receptors (CAR), which are comprised of an extracellular antibody part and an intracellular
T cell receptor signaling part, to genetically engineer T cells for
antigen recognition. Due to efficacy in other
tumor entities, a plethora of CARs has been designed and tested for
glioma, with promising signs of biological activity. In this review, we describe
glioma antigens that have been targeted using CAR T cells preclinically and clinically, review their drawbacks and benefits, and illustrate how the emerging field of transgenic TCR
therapy can be used as a potent alternative for
cell therapy of
glioma overcoming antigenic limitations.