Research

Glioblastoma is the most common primary brain tumor in adults. Even with aggressive management that includes surgery, radiation and chemotherapy, the median survival is only 20 months. Unlike systemic cancers like melanoma, immunotherapy has not had a significant impact on the outcomes of patients with glioblastoma. Myeloid cells are central to the innate and adaptive immune response to glioblastoma. In brain tumors, these cells directly elicit an anti-tumor response (phagocytosis, tumor cytolysis), release pro-inflammatory cytokines that recruit T-cells (e.g. IL-12), and also present tumor specific antigens at deep cervical lymph nodes resulting in tumor specific T-cell activation. In preclinical mouse models, intravenously administered human genetically modified macrophages (GEMs) expressing IL-12 traffic to, persist in and deliver IL-12 to the brain tumor microenvironment. This resulted in suppression of brain tumor growth and T-cell infiltration. We are now developing and using next generation modified macrophages to deliver other brain tumor therapeutics including oncolytic viruses, inflammatory cytokines and tumor antigens for cross presentation to T-cells. We are also using next generation modified macrophages to understand how endogenous circulating monocytes become polarized towards a pro-tumor phenotype following recruitment to the tumor micro-environment. Additional areas of research include spatial transcriptomics, in-vivo CRISPR-Cas9 screens and mouse models of spontaneous brain metastasis.