The Development of a Platform Designed to Activate NK Cells

Jeffrey Miller, MD, discusses the background of the Tri-Specific Killer Engager TRICK platform for the activation of natural killer cells for the treatment of refractory tumors, including those that are hematology-based.

Jeffrey Miller, MD, a professor of medicine in the Division of Hematology, Oncology, and Transplantation, deputy director of the Masonic Cancer Center, the Roger L. and Lynn C. Headrick Chari in Cancer Therapeutics, and associate scientific director of Molecular and Cellular Therapeutics at the University of Minnesota Medical School, discusses the background of the Tri-Specific Killer Engager TRICK platform for the activation of natural killer (NK) cells for the treatment of refractory tumors, including those that are hematology-based.

According to Miller, NK are lymphocytes in the body that have the ability to kill cancer cells. Research he has conducted has found that NK cells need to be more active in order to be affected, promoting the building of the TRICK platform. The platform is an immune engager that is meant to bind to the FC receptor on the NK cell surface called CD16.

Preclinical studies were done using an in vitro assay of acute myeloid leukemia targets of cell lines or primary cells. This led to the production of the GTB-3550 molecule, which was cleared by the FDA to be used in a clinical trial. 

0:08 | NKs are lymphocytes in the body, that have the capacity to kill cancer cells. I initially got involved in the NK field based on doing adoptive transfer. And one of the things that we realized after treating really hundreds of patients is that NK cells needed an additional specificity signal to be more active. So, this is when we really built this TRICK platform. So, it's an immune engager, that binds to the FC receptor on the NK cell surface called CD16. The key piece to why we think that this is so interesting to us is it's actually a combination drug, and it has an IL-15 sequence between the NK cell engager and the target cell engager. 

So, we first did a number of preclinical studies using an in vitro assay, using acute myeloid leukemia targets of either cell lines or primary cells. And this is really the background work that led up to the current study. We then produced the GTB-3550 molecule, got it cleared by the FDA and started a clinical trial.