More than a decade of research at the University of Minnesota to unearth and unleash a special kind of healing cell — the natural killer, or NK, cell — has produced two experimental cancer therapies that are being tested for the first time in patients.
The university is launching two new industry-funded clinical trials of NK cell products that it helped create. One is a protein cluster that coaxes the body’s own NK cells to fight leukemia; the other is an infusion of mass-produced NK cells to target solid tumors.
While both are still in the earliest stages of safety testing, university officials said they offer great promise because they could be “off the shelf” therapies for people with life-threatening cancers who can’t wait for transplants of NK cells from donors.
The wait for donor NK cells “is a major barrier,” said Dr. Manish Patel, the U researcher leading the solid tumor study. “They don’t have time to wait to find the donor and collect the cells and then grow the cells in the lab.”
The U in many ways is a grandfather of NK research, having been among the first U.S. institutions two decades ago to identify and pursue the cells as potential therapies. NK cells normally function as the first-strike weapons of the body’s immune system; they respond to perceived threats or infections while the body produces T-cells that provide more targeted attacks. NK cells also leave chemical trails that tell the T-cells where to go.
“It is one thing the U has really excelled in and led,” Patel said.
In the solid-tumor research, the U is the third site for a federally approved Phase 1 safety trial of an NK product called FT500, which it developed in a partnership with San Diego-based Fate Therapeutics. The cell therapy will be given on its own to one group of patients with solid organ cancers that haven’t responded to other treatments and to a second group of patients in combination with drugs that boost the immune system in a way that could make the NK cells more effective.
A common problem in any transplant or infusion is the body’s natural instinct to attack and reject them. NK cells had shown in research to resist this response, but mostly in patients with blood cancers such as leukemia, which had weakened their immune systems. Patients with solid cancer tumors tend to have stronger immune systems, though, which could attack the infused NK cells.
Researchers will closely monitor the duration of the NK cells in the body and how often they are rejected, said Dr. Dan Kaufman, a director of the cell therapy program at the University of California San Diego, who had previously conducted NK research in Minnesota. His institution is also participating in the Fate trial.
“The longer the cells persist, the more effective they tend to be,” he said.
Helping the body heal itself
The other new clinical trial involves a so-called TriKE cluster of proteins, developed by the U for GT Biopharma. It’s designed to strengthen NK cells in patients who have treatment-resistant leukemia.
“Our team has been working on the structure for years, and we are excited to see it in clinical testing,” said Dr. Jeffrey Miller, deputy director of the U’s Masonic Cancer Center, whose initial NK research led to both trials.
The university and Fate have three additional trials underway that involve the use of donor NK cells, which usually come from relatives of cancer patients.
NK cells are part of a new wave of immunotherapies that are designed to coax the body to heal itself. While NK cells are still experimental, another approach known as CAR-T therapies has already been approved and is in use at the U and Mayo Clinic. They involve harvesting T-cells from patients, modifying the cells, and then returning them to patients so the modified cells latch on to cancer cells and destroy them.
NK researchers said their alternatives, if proven effective, would be cheaper than the latest CAR-T therapies because they wouldn’t have to be customized for each patient.
The value of the NK cell research was often cited by the U a decade ago, when it was defending itself against state legislation to ban or restrict research using embryonic stem cells, the so-called master cells of the body that produce all other cells, including NK cells. Use of embryonic stem cells came under attack because they required the destruction of human embryos, which some viewed as human life requiring legal protection.
However, the NK product developed by the U for the new Fate trial comes from the stem cells of adults. The cells are reprogrammed to possess “pluripotent” capabilities — the ability to create other cells — typically found in embryonic stem cells.