on a rock with a pond behind them" width="910" height="555" />New cell therapies offer healing and hope where other approaches can’t reach.
"The healing that we’re seeing is remarkable,” says Dr. Amy Lightner, a colorectal surgeon and researcher who leads the new Center for Regenerative Medicine and Surgery in Cleveland Clinic’s Digestive Disease & Surgery Institute. | Photo: Yu Kwan Lee
If you want to start to wrap your head around the concept of regenerative medicine , look no farther than the nearest mirror.
When you get there, study your face. Done? Excellent. OK, now stop reading, let a few weeks go by and then have another gander at that mug of yours.
Go ahead — we’ll wait.
[a few weeks later]
Hello again! Did you notice much of a difference when you went back to the mirror? Probably not. Here’s the fascinating part, though: You’re the proud owner of a new face.
Sure, it looks familiar. But the cells that you previously saw on the surface of your visage are history. They’ve been replaced by fresh cells that got their start deep within your epidermis. They grew and divided and gradually made their way along a river of cells to the outermost layer of skin, where old cells that have died are continually sloughed off to make way for new cells.
It’s true: Our bodies know a thing or two about regeneration. And we’re learning more all the time, thanks to regenerative medicine. This burgeoning interdisciplinary field seeks to restore healthy form and function by repairing, replacing or rejuvenating cells, tissues or organs that are depleted, damaged or diseased.
“Regenerative medicine is really a catchphrase for a lot of different types of therapies,” says Timothy Chan, MD, PhD, Director of Cleveland Clinic’s Center for Immunotherapy and Precision Immuno-Oncology.
Broadly speaking, this isn’t an entirely new concept. Skin grafts, which originated in India some 3,000 years ago, could be considered a form of regenerative medicine. What is new is the ever-expanding menu of cell therapies that fall under the same umbrella.
“When we talk about regenerative medicine today, a lot of what we’re talking about is cell therapy,” says Dr. Chan, who also leads (with Stan Gerson, MD) the National Center for Regenerative Medicine, a Cleveland-based consortium whose founding partners include Cleveland Clinic, Case Western Reserve University and University Hospitals.
“Regenerative approaches are very important when you have to generate critical cells,” Dr. Chan says. “A lot of areas of investigation utilize stem cells, and it rolls into utilizing engineered T cells and other types of cells to elicit a fix for a disease.”
It could be cancer. Or multiple sclerosis. Or inflammatory bowel disease. With those diseases and others, regenerative medicine is bringing the promise of healing to more and more patients. Read on to meet three of them.
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For Kevin Kelley, the bad news came out of nowhere. “I woke up one morning,” he recalls, “and it felt like somebody had stuffed half a banana under the left side of my jaw.” The IT data security analyst from the Cleveland suburb of Rocky River, Ohio, considered himself to be in good health, aside from the hypertension that ran in his family and a recent pulmonary embolism that was successfully treated. A competitive swimmer, he swam a couple of miles almost every day, either in Lake Erie or in a pool.
A biopsy of Kelley’s swollen gland revealed an aggressive form of non-Hodgkins lymphoma, a malignant cancer that originates in the lymphatic system, a network of vessels, tissues and organs that helps remove toxins and waste from our bodies.
To fight the disease, Kelley and his oncologist, Brian Hill, MD, PhD, of Cleveland Clinic, turned to regenerative medicine — not once, but twice. “His case is compelling because it highlights where regenerative medicine has been and where regenerative medicine is heading,” says Dr. Hill, Director of the Lymphoid Malignancies Program in Taussig Cancer Institute.
Kelley received a bone marrow transplant and CAR-T cell therapy. Bone marrow transplants, which have been used for decades, transfer healthy blood-forming cells into a person with blood cancer. CAR-T cell therapy, which the Food and Drug Administration initially approved in 2017, modifies a patient’s own immune cells to kill cancer cells.
First, though, Kelley underwent six cycles of chemotherapy. Through it all, he continued to swim as often as he could. His care team even timed the treatments so he and his new bride, Karen, could enjoy a Grand Cayman honeymoon.
Unfortunately, a few months later, a biopsy showed that Kelley wasn’t cancer-free. The next step was a bone marrow transplant, immediately preceded by more chemotherapy. “Very high doses of chemotherapy are delivered with the intention of eliminating the lymphoma,” Dr. Hill says. “In the process, though, the patient’s bone marrow is eradicated, too. So you have to collect their bone marrow ahead of time and then give it back to them after the chemotherapy.”
In Kelley’s case, the transplant was autologous, meaning he was his own donor. (Allogeneic transplants entail a matched donor.) During the transplant, more than 100 million hematopoietic stem cells were delivered directly into his bloodstream through a special type of IV. For good measure, a chaplain blessed the cells beforehand, at Kelley’s request. “I figured every little bit helps,” he says.
Like salmon swimming upstream to spawn, the cells knew where to go and what to do when they got there, regenerating healthy marrow in the bones.
For Kelley, the road to recovery included a three-week stay in the hospital. After another month of rest at home, he began swimming again, slowly but surely regaining strength. He was declared in remission, although the respite was short-lived. Less than a year after the bone marrow transplant, a scan showed new activity. A lymph node biopsy confirmed it: The lymphoma was back.
Kelley didn’t hesitate when Dr. Hill recommended a new line of attack: CAR-T cell therapy. To get the ball rolling, T cells — which are white blood cells — were collected from Kelley through a procedure called leukapheresis. The T cells were then shipped off to a lab, where they were genetically altered. New chimeric antigen receptors (CAR for short) on the surface of the T cells would allow them to carry out a seek-and-destroy mission against cancer cells. In the meantime, Kelley had another course of chemotherapy. When the manufactured CAR-T cells were ready, hundreds of millions of them were infused into his bloodstream. After a week in the hospital, he was back home and on the mend.
“With CAR-T cell therapy, instead of just hammering away at the cancer cells with traditional chemotherapy drugs that poison the cells, the idea is to invoke the power of the body’s own immune response to attack the cancer,” Dr. Hill says.
By way of an explanation, Kelley offers an analogy that any fan of old-school video games will appreciate: “Suddenly, your body is playing Pac-Man. Once those manufactured T cells are put in you, they’re on the hunt. When they find a cancer cell, they destroy it. They’re just gobbling it up.”
CAR-T cell therapy isn’t without side effects, which can include flu-like symptoms as well as neurologic events that can result in confusion. Nonetheless, this particular form of regenerative medicine shows great promise. “I’m very optimistic for the future of this treatment approach,” Dr. Hill says.
As for Kelley, he’s back in remission. He plans to swim in a couple of upcoming 8-mile, open-water races: one in the Florida Keys and one around Mackinac Island in Michigan. The latter will be a fundraiser for the Leukemia & Lymphoma Society.
“I feel great,” Kelley says. “Now it’s time to go have some fun.”
