Engineering NK cells as a novel cancer immunotherapy
Current work in our laboratory centers on developing novel strategies to enhance NK cell effector function against various tumors by genetically engineering the cells to enhance their anti-cancer activity and persistence. We are pursuing this by engineering NK cells to express CAR against multiple cancer targets. Our laboratory recently demonstrated that ex vivo expanded NK cells expressing a CAR against CD19 and the IL15 gene can dramatically enhance the in vivo persistence and anti-tumor activity of CAR-NK cells in a mouse model of lymphoma. We have translated this strategy to the clinic and a first-in-human clinical trial is currently underway at our center.
Adoptive therapy using viral specific T cells
Another area of interest in our laboratory is the use of virus-specific T cells as adoptive therapy for the treatment of viral infection. Allogeneic stem cell transplantation is a potential curative treatment for hematologic malignancies including leukemia and lymphoma but a number of factor such as the high mortality rates associated with viral infection and graft vs host disease (GVHD) after transplant limit the clinical success. Our goal is to develop engineered T cells using different gene editing tools including TALEN or CRISPR to make them resistant to current cancer immunosuppressive drug regimens and use it as an off-the-shelf T cell therapy for immediate clinical use. Data from our clinical trial of off-the-shelf BKV-specific T-cells for the treatment of progressive multifocal encephalopathy (PML) was recently published in the New England Journal of Medicine.