Jeffrey Miller, MD

“There used to be a paucity of industry interested in NK cell biology and now that's exploded. Now, everybody's interested in autologous NK cells or induced pluripotent stem cells-derived NK cells.”

Natural killer (NK) cell approaches are being investigated more and more for treating both hematologic malignancies and solid tumors. Presentations on new NK cell approaches were given at the 

European Society of Medical Oncology (ESMO) Congress 2022

, held September 9-13, in Paris, France. One such presentation was given by Jeffrey Miller, MD, professor and deputy director of the Masonic Cancer Center of the University of Minnesota, on GTB-5550, a B7H3 tri-specific killer engager (TriKE) that specifically stimulated expansion of natural killer (NK) cells in preclinical models of multiple cancers.

The novel dual camelid (cam) TriKE contains wild type interleukin-15 and 2 cam engagers that target CD16 on NK cells and B7H3 on multiple solid tumors. The data presented demonstrated GTB-5550'sability to increase activity of NK cells against cancer cells after stimulation.

 spoke with Miller to learn more about NK cell research and other promising approaches discussed at the ESMO Congress. He touched on new avenues of research including NK cell combinations with PD1 blockades and different platforms to produce NK cells.

Click here to read more coverage of ESMO Congress 2022.

Miler JS, Zorko N, Merino A, et al. B7H3-targeted tri-specific killer engagers deliver IL-15 to NK cells but not T-cells, and specifically target solid tumors as a pan-tumor antigen strategy mediated through NK cells. Presented at: ESMO Congress 2022, September 9-13, Paris, France.

Videos

The deputy director of the Masonic Cancer Center discussed trends of presentations from ESMO 2022. 

Jeffrey Miller, MD, on Emerging Research With Natural Killer Cells 

“We learned [in a previous study] that the immune engager to the NK cell is critically important. And while that study was ongoing, we discovered that if we took a nanobody, single domain antibody to engage CD16, we had significantly greater potency. So that's really the premise for putting this together.”

GTB-5550, a B7H3 tri-specific killer engager (TriKE) specifically stimulated expansion of natural killer (NK) cells in preclinical models of multiple cancers. These data were presented at the 

, held September 9-13, in Paris, France, by Jeffrey Miller, MD, professor and deputy director of the Masonic Cancer Center of the University of Minnesota.

GTB-5550 is a novel dual camelid (cam) TriKE that contains wild type interleukin-15 as well as 2 cam engagers to target CD16 on NK cells and B7H3 on multiple solid tumors. Miller and colleagues demonstrated increased activity of NK cells against cancer cells after stimulation with the TriKE engager.

spoke with Miller to learn more about the study’s results and the importance of improving targeting and engagement of NK cells with antibodies. He also discussed the potential for a clinical trial in the near future investigating the approach.

The deputy director of the Masonic Cancer Center discussed the preclinical findings of his study on a TriKE engager and NK cells. 

Jeffrey Miller, MD, on Engaging NK Cells in Solid Tumors 

“We've been really trying over and over to get these cells to be metabolically active and change their characteristics so they would survive longer based on the premise that we think survival for some finite period of time is going to be important for clinical activity.”

Allogeneic, natural killer (NK) cells are emerging as an area of research for treating hematologic and solid malignancies. Fate Therapeutics is developing multiple NK, chimeric antigen receptor (CAR) T-cell, and CAR NK therapies for these indications and has worked closely with researchers from the University of Minnesota School of Medicine to develop their off-the-shelf NK cell therapies.

Jeffrey Miller, MD, professor of medicine, division of hematology, oncology, and transplantation, University of Minnesota School of Medicine, presented data on their research with NK cells as well as some updates on Fate’s clinical trials at the 

, held June 29-30 in Boston, Massachusetts. 

 spoke with Miller to learn more about the advantages of NK cells in hematologic and solid malignancies. He discussed further research he wants to pursue with NK cells and shortcomings that need to be addressed.

Miller J. iPSC-derived NK cells to treat cancer. Presented at: OCTS USA 2022, June 29-30, Boston, MA.

The professor of medicine and University of Minnesota Medical School discussed the advantages and unmet needs of natural killer cells in oncology. 

Jeffrey Miller, MD

Articles

Jeffrey Miller, MD, on Emerging Research With Natural Killer Cells

Jeffrey Miller, MD, on Engaging NK Cells in Solid Tumors

Jeffrey Miller, MD, on Improving NK Cells for Solid and Hematologic Malignancies