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THE NATURAL KILLER CELL
The natural The natural
Killer Killer
Local researchers are investigating a new treatment that could wipe out various cancers, brain tumors, viruses and more
Cell
prospective, formidable weapon a a against cancer which is a natural part of the human immune system is capturing the attention and excitement of researchers conducting clinical trials at Nationwide Children’s Hospital and Ohio State University’s
Comprehensive Cancer Center. Aptly named, natural killer cells—NK cells— are part of the immune system residing in the family of white blood cells known as lymphocytes, which protect the body against disease, bacteria, viruses and other foreign invaders.
While other members of that family, such as
T cells and B cells, will attack specific toxins,
NK cells will assault any alien substance that invades the body. Heightening the enthusiasm of researchers are early results that suggest administering massive doses of NK cells to cancer patients has few, if any, side effects.
Dr. Dean A. Lee, director of cellular therapy and the cancer immunology program at Nationwide Children’s and OSU’s Comprehensive Cancer Center, calls NK cells the “first responders” to infection. While his main focus is investigating these cells as a potential cancer weapon, other studies are probing their clout as a means for fighting COVID-19.
“These cells look for and can recognize any signs of stress or abnormal DNA or metabolism,” Lee says. “They have an internal ability to recognize a cancer cell and kill it.”
The research is vital. In 2020, more than 1.8 million new cancer cases were expected in the U.S., and more than 600,000 people were expected to succumb to the disease. Nearly 40 percent of all people will be diagnosed with cancer in their lifetimes, according to the National Cancer Institute. But cancer treatment has long relied on highly toxic treatments, such chemotherapy, which kills both good and bad cells. That’s why research into NK cells has become even more valuable.
Lee is collaborating with a dozen other physician researchers at Nationwide Children’s and OSU on clinical trials for sarcoma, melanoma, acute myeloid and chronic lymphocytic leukemias, brain tumors, neuroblastoma, lymphoma and viral infections.
“Implementing cell therapy clinical trials requires a broadly integrated team approach to bring in the necessary intellectual property, clinical manufacturing, regulatory support, finances and clinical care,” he says. “We now have a truly joint program between the two institutions across these aspects.”
While NK cells were discovered in the 1970s, Lee was working on trying to grow T cells around 2007 when he unexpectedly saw “a bunch” of NK cells growing, which he initially ignored. “They were like weeds,” he says, regarding their fast growth.
A mentor encouraged him to intentionally grow NK cells because the process was challenging, if not impossible at the time. Lee overcame those challenges and now grows 10,000 to 50,000 NK cells in a few weeks. Because they can be frozen, he has been able to develop banks of NK cells, which other researchers can use in their work.
The experimental treatments require large numbers of cells. Patients typically receive about 5 billion NK cells in a single dose, which they seem to tolerate well. As of September, 16 patients were enrolled in local studies, while five clinical trials had been completed in Houston and one in Brazil.
“Totally, a little more than 400 NK cell infusions have been delivered to just over 100 patients,” Lee says. “As for side effects, there are almost none. We are not aware of anyone who has a major toxicity to the infusion.”
Dr. Timothy Cripe, chief of the division of hematology and oncology at Nationwide Children’s Hospital, says Lee’s work is one of the more unique and robust studies in cellular therapy.
“This is harnessing the power of the immune system and redirecting it to a cancer, and that is a relatively new thing to do. Most cancer therapies poison the cancer and harm normal cells,” Cripe says.
Not only has Lee been able to massively increase the availability of NK cells for research, he has also improved their strength. A tumor can suppress and inhibit an NK cell, but Lee has boosted their ability to resist those defenses.
“It’s like building an army. If you have one soldier, they will not do very well but if you have thousands of soldiers, they do much better,” Cripe says. “Dr. Lee has discovered how to turn one soldier into thousands, and he is arming them with more weapons and more shields.”
That army includes NK cells not yet tested on humans. Instead, those are being directly injected into the cancerous tumors in dogs. As of last fall, the Food and Drug Administration had approved three studies using these specific NK cells for human tests.
The canine trials focus on bone cancer. Dogs make good subjects because, like humans, cancer occurs naturally and up to 10 times more often than in people, says Dr. William Kisseberth, a professor of medical oncology at OSU’s College of Veterinary Medicine.
“Our trial is designed to answer the safety of the therapy and to determine how high of a dose we can do,” Kisseberth says. “One of the things we are able to do in a dog clinical trial is to give NK cells to the dogs in greater frequency than in most previous human trials.”
The dogs receive standard care for any dog with bone cancer but with both dog and human trials ongoing, “We learn things from the human stud-
—DR. TIMOTHY CRIPE, CHIEF OF THE DIVISION OF HEMATOLOGY AND ONCOLOGY AT NATIONWIDE CHILDREN’S HOSPITAL
ies that help with the dog studies and vice versa,” Kisseberth says.
Dr. Bhuvana Setty, who is the principal investigator at Nationwide Children’s for a clinical trial established by the National Pediatric Cancer Foundation, says researchers are desperately working to get more effective and less toxic treatments that quickly work well.
“We’ve had a lot of clinical trials in the last couple of decades where we really struggled to make a significant impact with relapses,” says Setty, who focuses on patients with sarcomas, a cancer that begins in the bones or soft tissue.
Relapse rates for patients where that cancer is local is typically 30 percent to 40 percent in the first five years, but that number increases dramatically if the cancer has spread, with the chance for relapse in the 85- to 90-percent range, Setty says.
Last fall, Setty was working on finalizing a clinical trial in collaboration with Lee that could begin in the second quarter of 2021, using NK cells to treat up to 30 patients with sarcoma.
“This is very novel because NK cells have not been previously used for patients with sarcoma,” Setty says. “This is very different research from other immune therapy trials being run across the country.”
Dr. Sumi Vasu, an associate professor of internal medicine at OSU, began studies last June that will involve up to 50 people. She treats patients with acute myeloid leukemia and time is often an enemy, so having access to NK cells in a bank instead of spending weeks finding a matching donor is vital.
“People can be healthy and then critically ill in three weeks, so things can turn quickly,” she says. “The [cell] product is already there and there is no time spent looking for a donor. To me, that is the most innovative aspect of this trial to be able to help a sick population in a timely way.”
In the fall, Dr. Kari Kendra, also an associate professor of internal medicine at OSU, was working on approval for a study to use NK cells against brain tumors that develop from metastasized skin cancer.
The immune system is incredibly important in controlling melanoma, and the work with NK cells is providing researchers a potential method to develop even more benefit from that system, she says.
“Our goal in treating cancer is to control the disease as long as we can, the best that we can, with a quality of life that is acceptable,” Kendra says. “These immune-therapies, especially the NK therapies, offer the potential way to do that with minimal toxicity and a longer duration.” ✚
