Gliomas are the most common primary brain tumors. Therapies remain very challenging given the paucity of targetable molecules since not all cells within a tumor can be targeted in the same way, and not all tumors express the same targets. Research at UCSF has led to the identification of the tumor-specific isoform RAD54B, a DNA repair and recombination protein, which is uniformly expressed at high levels in a vast majority of malignant gliomas. T cells expressing RAD54B-specific TCRs were generated and initial proof of concept studies have shown promise. This invention has the potential to improve the effectiveness of immunotherapy for glioma in clinical populations.