Abstract
Immune surveillance of the brain is regulated by resident non-neuronal cells and the blood-brain barrier. 1 Dys-regulation of immunosurveillance is a hallmark feature of several diseases 2–5 including brain tumors 6 that interact with and rely heavily on immune cells, 7 suggesting that disrupting the neuroimmunology of tumors could slow their progression. Yet few tools are available to control brain immunology in vivo with local precision, and fewer yet are used for therapeutic intervention. 2 Here, we propose engineered cytokines as a neuroimmune-modulation platform. We demonstrate that the residence time of cytokines in the brain can be tuned by binding them to the extracellular matrix or synthetic scaffolds. We then show that the aluminum hydroxide adjuvant (alum) is retained in the brain >2 weeks. Tethering of inflammatory cytokines such as interleukins (IL) 2 and 12 to alum yields extended neuroinflammation and brain immunosurveillance after intracranial administration, while avoiding systemic toxicity. In mouse models of both immunologically hot and cold brain tumors, the intracranial deposition of alum-tethered cytokines causes significant delay in tumor progression. RNA profiling reveals that engineered cytokines engage both innate and adaptive immunity in the brain. These findings suggest that engineered cytokines can reprogram brain immunosurveillance, informing the development of future therapies for neuroimmune diseases.
Polina Anikeeva
Matoula S. Salapatas Professor and Head, Department of Materials Science and EngineeringProfessor, Brain and Cognitive SciencesDirector, K. Lisa Yang Brain-Body CenterAssociate Investigator, McGovern Institute for Brain ResearchAssociate Director, Research Laboratory of Electronics
My goal is to combine the current knowledge of biology and nanoelectronics to develop materials and devices for minimally invasive treatments for neurological and neuromuscular diseases.