
This week, we profile a recent publication in Nature Biotechnology by Dr. Rizwan Romee from the Department of Medical Oncology at Dana-Farber Cancer Institute (DFCI). Dr. Romwee is a part of the NK Cell Therapeutics Initiative Program at DFCI, where he and his team investigate Natural Killer cells using synthetic biology approaches to enhance their anti-tumor function.
Can you provide a brief overview of your lab’s current research focus?
I am a cancer immunologist and my lab uses synthetic biology and gene editing tools to develop next-generation immunotherapies for cancer. Some of these approaches include incorporating novel gene constructs in CAR NK and CAR T cells for both direct cancer targeting and modulating otherwise highly immunosuppressive tumor microenvironments (TME). More recently, we have engineered nonpathogenic bacteria to selectively deliver potent cytokines like IL-15 and IL-18 to the tumors. This leads to potent activation of CD8+ T and NK cells alone and synergistically with PD-1 blockade, curing a significant proportion of mice bearing colorectal cancer and melanoma.
What is the significance of the findings in this publication?
This is a brand new modality of immunotherapy based on surface displaying potent cytokines and other biologics on the outer membrane of nonpathogenic E. coli to target tumors with otherwise very poor prognoses. Furthermore, this treatment also works synergistically in combination with checkpoint blockade and as a “GPS” guiding CAR NK cells to tumors. In the current publication, we primarily focus on displaying cytokines; however, it is a “plug and play” system that can be used to display a wide variety of biologics for even non-cancer applications.
What are the next steps for this research?
We are currently focusing our efforts on translating this very promising treatment in a phase 1 clinical trial. We are considering both topical and systemic routes of administration of our engineered bacteria, in multiple cancer types.
If you’d like us to mention your funding sources, please list them.
This work is a collaboration with Prof. Jiahe Li’s group at the University of Michigan, Ann Arbor (he was previously at the North Eastern University). This work was funded by the NIH and the DFCI-NEU Collaboration Grant. Institutional support was provided by Dana Farber Cancer Institute.