DAC treatment of intracranial glioma-bearing mice permits trafficking of NY-ESO-1 TCR engineered T cells through the brain parenchyma. Mice with 1-week established intracranial U-251MG were treated with a vehicle control (DAC−) or with 10 mg/kg DAC i.p. × 3 days (DAC+). NY-ESO-1 TCR-transduced T cells were injected into the opposite hemisphere of the brain 2 days following the last DAC administration; 24 h later, the animals were sacrificed and the brains removed, sectioned, and immunolabeled for human CD3 and CD8. (A and B) Coronal sections (mag = 1×) stained with hematoxylin and eosin in mice given (A) control treatment or (B) DAC. (C–F) Injection of NY-ESO-1 TCR-transduced T cells into the hemisphere contralateral to the tumor implantation site at 2 days following the DAC treatment shows migration to contralateral human glioma xenografts. (C and D) DAC– group show lack of T cell infiltration into tumor, while (E and F) DAC+ group show trafficking through white matter (mag = 10×). Scale bar = 1 mm (A and B), 250 μm (A and B inset), and 50 μm (C–F). Data shown are representative of one experiment repeated twice with similar findings.