Welcometo the Romee Lab for Immune Cell Gene Manipulation and Therapy
Research focus of our lab is to use novel synthetic biology approaches to manipulate immune cells including Natural Killer (NK) and T cells to enhance their anti-tumor function. Using CRISPR and non-CRISPR based gene editing approaches we are developing novel secondary arming strategies aimed at overcoming immunosuppressive tumor microenvironment as well as enhacing immune cell trafficking into the solid tumors. We are also developing synthetic cytokines with novel immune modulatory properties aimed at overcoming immune dysfunction. More recently we have engineered non pathogenic gut bacteria (E coli K12 DH5a) to surface display key cytokines including IL-15, IL-18 and IL-21 as a novel form of immunotherapy which is not only safe but also demonstrates enhanced tumor enrichment (10,000x), induces potent CD8+ T cell and NK cell mediated anti-tumor responses while also boosting tumor trafficking and responses to CAR NK cells in pre-clinical mouse models (Yang et al, Nature Biotech 2024, https://pubmed.ncbi.nlm.nih.gov/39367093). This bacterial engineering is part of our ongoing collaboration with Prof. Jiahe Li's group at the University of Michigan, Ann Arbor.
As part of the DFCI's NK Cell Therapeutics Initiative Program, we are evaluating memory-like NK cells in combination with novel immune-modulatory agents in patients with advanced malignancies including AML, MDS, platinum refractory head and neck cancer and multiple myeloma. Using flow cytometry, mass cytometry and single cell RNA sequencing on the samples collected from these studies allows us to study key aspects of the in vivo biology of the adoptively transferred memory-like NK cells and their interaction with other immune cells present in the tumor microenvironment. We hope this information will guide us in designing future NK cell based clinical protocols.