UMN-developed protein that fights blood disorders to be tested on humans

Human clinical trials have opened to test the TriKE protein, which activates natural killer cells and targets tumors.

Morgan La Casse

Morgan La Casse

by Joe Kelly

Human clinical trials are now open for a protein that University of Minnesota researchers developed to fight a type of leukemia. 

The protein, called tri-specific natural killer engagers, or TriKE, specifically targets the blood disorders acute myeloid leukemia,  myelodysplastic syndrome and systemic mastocytosis. Patients are currently being screened for eligibility to participate in clinical trials of the protein.

The clinical trial is specifically for patients who have already been through standard therapies and are physically strong enough for testing the TriKE protein, said Erica Warlick, a University associate professor of medicine who is in charge of the clinical trials.

Some people are being screened for the trial, but some need more chemotherapy or other treatments before testing the protein, Warlick said. Although no one has been tested yet, the researchers are hoping someone will meet the qualifications for the trial within the next several weeks.

Previously, researchers tested the protein on mice, but this will be the first time they test it on humans, said Martin Felices, a University assistant professor of medicine who helped develop the protein. 

“Nobody has tested these types of molecules before, so there’s a lot of excitement,” he said. 

The TriKE protein was developed by Jeffrey Miller, a University professor and deputy director of the Masonic Cancer Center, Felices and University professor and researcher Daniel Vallera. TriKE is designed to activate the body’s natural killer cells, or NK cells, to target tumor cells.

“Essentially what natural killer cells do is they patrol the body and look for cells that have changed … through mutation to eventually become tumors, and they tend to kill those cells,” Felices said. “One of the tricky things about natural killer cells, even though they can kill certain cells during their patrol, they are not antigen specific, which means that they can’t find very specific tumor antigens.”

TriKE does two things: it forms a bridge between NK and tumor cells so that the NK cells can target and kill the tumor, and it tells NK cells to replicate, Felices said.

“The more natural killer cells you have, the better you’re going to kill the tumor, particularly when you give them this bridge,” Felices said.

Despite opening clinical trials for TriKE, the team is still working on improving the protein. Felices said the researchers hope to have the protein target other tumors as well.

“The neat thing about these molecules … we can change out the arm that attaches to [leukemia] and put in an arm that attaches to something that targets lung cancer or prostate cancer or breast cancer,” Felices said. “That’s our hope, that’s the big hope.”

Miller and his colleagues have been researching NK cells for two decades and started development of TriKE five years ago.

Miller said it was a collaborative effort among the researchers to get the protein approved for clinical trials. 

“It’s what we’re calling in this day and age …  team science,” Miller said. “There’s just lots of moving pieces … It’s a really really big effort to get something from the laboratory idea to translate completely into patient care.”