Both our in vivo data as well as our results in an ex vivo BBB model align with the swift leakage of rIL-12 from the brain tumor parenchyma as reported by Chiocca and colleagues during local IL-12 gene therapy13, and demonstrate a significant reduction of such transport in the case of the FcRn-silenced IL-12Fc variant NHQ. Here, FCGRT is linked to brain neoplasm.