Fighting Back Against Childhood Cancer

Sunday, Nov 24 2019

Dr Terry Fry

Jalen is exhausted. He’s been living with leukemia for a year and a half, and the treatments never seem to get any easier. Chemotherapy has done its job of sending his cancer into remission, but the powerful medicines leave him nauseous and worn out. He’s missed more school days than he can count.

“I wish there was an easier cure,” says Jalen, age 9.

While he gets his bi-weekly chemo infusions at Children’s Hospital Colorado, a team of physician-scientists on the Anschutz Medical Campus are working tirelessly to make Jalen’s wish a reality.

Led by Dr. Terry Fry, researchers are working to turn our immune systems into cancer-fighting machines.

Their work has the potential to drive radical progress in treating and curing pediatric cancer — and that could mean a future in which kids like Jalen could be cured without chemotherapy.

Cancer’s Worst Enemy

Physician-scientists at Children’s Hospital Colorado are gaining ground on pediatric cancer by using an unexpected weapon: the body’s own immune system.

Dr. Fry is one of the world’s preeminent investigators of immunotherapy, a promising new treatment approach that harnesses the body’s own immune system to fight cancer and other diseases. As Director of Cancer Immunotherapy on the Anschutz Medical Campus, Dr. Fry is discovering new ways to train the body’s cancer-fighting T-cells to hunt down and kill cancer cells.

In recent decades, survival rates for the most common form of pediatric cancer, acute lymphoblastic leukemia (ALL), have increased to nearly 90%. For the 10% of children who relapse or whose cancer doesn't respond to chemotherapy, survival rates plummet dramatically. Even for kids who are cured, chemo often leaves behind lifelong side effects.

With the help of philanthropy, Dr. Fry is changing the future for kids fighting cancer. He was among the first scientists to investigate an emerging immunotherapy treatment known as CAR-T cell therapy. He helped to develop the world’s first commercially available cancer gene immunotherapy: a chimeric antigen receptor (CAR) that targets a specific protein found on the surface of leukemia cells, CD19.

“With this therapy, we remove the immune cells from the patient and then genetically modify them,” explains Dr. Fry. “We redirect the cells to find the tumor. Then we reinfuse those cells back into the patient. We’re essentially supercharging the immune system to seek out and destroy cancer cells.”

The initial results of this new therapy are unprecedented.

Approved by the Food and Drug Administration (FDA) for pediatric use in 2017, the CD19 CAR therapy achieved an astonishing 80-90% remission rate in leukemia patients whose cancer didn’t respond to traditional chemotherapy in just 4 months of treatment. Moreover, patients in the trial were able to avoid many of the harsh, painful effects of chemo.

“Traditional chemotherapy is effective but toxic,” says pediatric oncologist and The Barton Family Endowed Chair for Bone Marrow Transplant, Dr. Michael Verneris, another primary investigator of the CD19 CAR. “And in some cases, it’s actually not effective.”

The Children’s Colorado Center for Cancer and Blood Disorders is now infusing patients with the CD19 CAR therapy every month. We are one of only five sites in the nation providing this life-changing immunotherapy treatment, which could be a game changer for the way we treat pediatric cancer.

If you ask Dr. Fry, he’ll tell you that this is just the beginning.

Building a Better CAR

Subsequent studies on the CD19 CAR therapy showed that about half of patients treated later relapsed. Their modified T cells died off, the leukemia cells mutated to resist them, and the cancer returned.

"We're using the patient's own cells as the material to make this therapy, and sometimes you get a bad cell,” explains Dr. Fry.

Today, Dr. Fry is working on immunotherapy treatments that decrease cancer resistance and improve the likelihood of keeping cancers in remission. For the patients who relapsed after the CD19 CAR therapy, Dr. Fry developed a new CAR treatment that targets a different protein found on the surface of leukemia cells, known as CD22. Currently in clinical trials, initial studies show that 85% of patients went back into remission with the CD22 CAR therapy.

With these promising results, Dr. Fry’s new therapy was recently granted breakthrough designation by the FDA, which will fast-track its development and make the CD22 CAR commercially available to more children sooner — including patients at Children’s Colorado.

Dr. Fry is also working to apply his findings to other cancers. His lab is developing a CAR targeting a protein expressed by acute myeloid leukemia (AML) cells. The FDA has already approved a clinical trial of this new therapy for children with relapsed AML. The multisite trial, which includes Children’s Colorado, is expected to open in the coming year.

Endless Possibilities

The way Dr. Fry sees it, childhood leukemia is just one of many potential applications of immunotherapy. His lab is in discussions with fellow research teams studying brain tumors and solid tumors. The goal is to expand the lab’s success with immunotherapy in treating other types of cancers — and even adult conditions.

“Treatment for autoimmune diseases involves manipulating the same cells we’re studying,” says Dr. Fry. “This absolutely has potential beyond cancer and pediatric illnesses.”

Dr. Fry’s lab also continues to expand its treatment arsenal for acute lymphoblastic leukemia, aiming to improve remission durability.

“Our lab is rolling out a therapy that targets both the CD19 and CD22 proteins, so we can treat all types of acute lymphocytic leukemia,” said Dr. Fry.

Currently in proof-of-principal phase, this therapy is showing promising early results. Clinical trials are projected to begin enrolling patients at Children’s Colorado in spring 2020 — the first trial of its kind on the Anschutz Medical Campus.

“Instead of a 50% remission rate at one year, maybe we can get up to 75%. Then maybe some patients don’t have to undergo chemo at all. This is our vision.”

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