Research focus of my lab is gene manipulation of the human Natural Killer (NK) cells to enhance their anti-tumor function and simultaneously modulate the tumor microenvironment (TME). NK cells are historically resistant to transduction, however my lab has recently optimized a lenti-virus based protocol achieving high transduction rates in the peripheral blood primary NK cells. My lab is closely collaborating with Professor Jianzhu Chen's group at MIT (https://chen-lab.mit.edu) to develop next generation CAR constructs with novel immune modulating functions. We are also developing a novel class of immuno-cytokines aimed at selectively targeting the immuno-suppressive cells like MDSCs and Tregs.
We described human memory-like NK cells with enhanced anti-tumor activity and in a first in human clinical trial demonstrated safety and promising activity of these cells in advanced AML patients. We are currently testing these memory-like NK cells in combination with novel immune-modulatory agents in patients with advanced malignancies. 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.
I also lead our haploidentical transplant program and we are developing protocols using haploidentical donor transplantation as a platform to incorporate memory-like NK cell-based immunotherapy approaches.