Jeffrey Miller, MD

Summary
Dr. Miller has been interested in NK cell biology, NK cell development, the acquisition of NK cell receptors and seamless translation into clinical trials throughout his entire academic career. Currently, the lab is focused on mechanisms which determine the enhanced function seen with CMV induced adaptive NK cells, facilitating immune synapses with IL-15 containing Trispecific Killer Engagers (TriKEs), IL-15 biology, NK cell killer immunoglobulin receptor (KIR) acquisition and function (NK cell education), and developing NK cell therapeutics.

Throughout his career at the University of Minnesota, he has mentored faculty and delivered hundreds of NK cells products to patients with cancer. His team has identified unique NKC2C+ NK cell repertoires exhibit a methylation signature of CD8+ T cells with properties of immune memory. Adaptive NK cells are distinctly different from canonical NK cells and signal through CD16 using a dominant CD3? signal by downregulation of FcR?R1?. Adaptive NK cells are better primed for killing, cytokine production, ADCC and exhibit unique metabolic signatures that enhance their survival. He has developed state-of-the-art functional readouts to study NK cells from the laboratory and the clinic based on high resolution testing. He was the first to report that haploidentical allogeneic human NK cells can persist and expand for up to one month after adoptive transfer. Based on these studies a significant part of his effort is trying to understand how to exploit NK cells for therapeutic purposes against infection and cancer and how to improve outcomes from allogeneic hematopoietic cell transplantation.

Clinically, he has developed first-in-human trials using allogeneic donor NK cells, rhIL-15, IL-15/IL-15R?-Fc (ALT-803, now called N-803), an NK cell TriKE that engages NK cells and AML targets that costimulates NK cells with an IL-15 linker. Dr. Miller's experience and translational expertise has supported a transition from individual related donor NK cell products to induced pluripotent stem cell (iPSC) derived NK cells. Advantages of using this off-the-shelf platform include the flexibility of multiple gene edits, immediate cryopreserved product availability, multi-doing strategies and combinatorial therapy with targeted agents to enhance NK cell function.

Dr. Miller is devoted to team science and mentoring. He has supervised > 400 NK cell products and sponsored >10 INDs and his team has studied >4000 transplant patients. Dr. Miller's experience, NIH grants and translational expertise provides a rich environment for training.