The Current and Future Promise of Immunotherapy for Childhood Cancers

The 1st article in a 3-part series on recent developments and ongoing research in immunotherapy for childhood cancers.

little boy with stuffed animal sits on hospital bed and gets chemotherapy

In the last 10 years, there’s been a lot of progress in the treatment of childhood cancers. Survival rates have increased from 60% to 90% for certain cancers since the mid-1970s.

Many children with cancer have a good response to standard treatments, including chemotherapy and radiation. But treatment stops working in some children. And in other children, standard treatments never work at all. For these children, there aren’t many other treatments to try.

That’s why there’s a lot of excitement about the rapid advancement in immunotherapies. This group of treatments uses the body’s natural protective system to attack cancer cells.

CAR T-cell therapy

One type of immunotherapy that’s gaining traction in the treatment of childhood cancer is CAR T-cell therapy. This cell therapy is also known as a gene therapy. CAR T-cell treatments involve modifying specific genes in immune cells called T-cells, a type of white blood cell. The treatment involves:

  • Removing a sample of blood or just white blood cells from the patient
  • Re-engineering the patient’s T-cells in a lab to arm them with new receptors on their surface, called chimeric antigen receptors, or CARS. The new CAR T-cells will be able to recognize and destroy cancer cells.
  • Multiplying the CAR T-cells to increase their numbers so they can attack more cancer cells
  • Infusing these genetically modified cells back into the patient

Once inside the body, the CAR T-cells should make more CAR T-cells. That way,  the treatment can keep working long after the infusion.

Researchers have been testing CAR T-cell treatments in clinical trials for years. Yet, it was only recently that this gene therapy was approved for use by the US Food and Drug Administration (FDA). The new drug is Kymriah (pronounced Kim-RYE-ah), with the generic name tisagenlecleucel. Kymriah was approved for certain children, adolescents, and young adults with B-cell acute lymphocytic leukemia (ALL).

The FDA approval is likely to be the first of many for CAR T-cell treatments and other immunotherapies for childhood cancers. Several treatments are in various stages of research and testing.

What's in a name?

Each part of Kymriah’s generic name – tisagenlecleucel – references how the drug is made, though not in order:

  • -cel shows the drug is a type of cell therapy
  • -leu- refers to white blood cells. The drug’s first components are T cells from the patient. T-cells are a type of white blood cell with immune properties.
  • -gen- means the drug involves a transfer of genetic material. In a special lab, the removed T cells are genetically reprogrammed to recognize a specific antigen on leukemia cells and other cells with
    CD-19. (The word antigen can also help you remember its role. Think antibody generator.)
  • -lec- refers to the way the cells are duplicated and tested for quality
  • tisa- is the only unique part of the name

The promise of immunotherapy

“Immunotherapy offers great promise for new cures in children,” says Susanna Greer, PhD, the director of the Nutrition and Immunology grants program at the American Cancer Society.

For treatment, we often have to teach the immune system how to recognize the enemy, and that's exactly what re-engineering T-cells into CAR T-cells is supposed to do.

Susanna Greer, PhD - Director, Nutrition and Immunology grants program, American Cancer Society

“Your immune system kills foreign invaders, like bacteria and viruses, all the time without you knowing it,” Greer explains. But the immune system doesn’t always recognize a cancer cell as an invader.

“For treatment, we often have to teach the immune system how to recognize cancer cells as the enemy,” says Greer. And that’s exactly what re-engineering T-cells into CAR T-cells is supposed to do. With Kymriah, for instance, the T-cells are engineered to look for leukemia cells that have the protein CD19 on them and kill them.

The hope is that the CAR T-cells continue to survive and duplicate in the body. That way, the immune system stays ready to kill any leukemia cells that try to come back

Potential risks

Like every treatment, CAR T-cell treatments and other types of gene therapy have risks. The biggest is the body’s response to such a big attack from the immune system. “CAR T-cell treatments cells lyse cancer cells. That means the cancer cells sort of explode. As they do, a lot of toxic substances flow into the blood and lymph systems,” Greer says. In turn, the immune system revs into full action to get rid of all those toxins.

This aggressive work by the immune system can lead to a response in the body called cytokine release syndrome (CRS). Symptoms of CRS can include high fever, trouble breathing, and neurological events. The symptoms can become life-threatening. That’s why the FDA expanded the approval of the drug Actemra (tocilizumab) at the same time it approved Kymriah. Actemra  can now be used to treat the symptoms of CRS. During clinical trials, 69% of patients had complete recovery from CRS within 2 weeks after 1 to 2 doses of Actemra.

New immunotherapies aren’t for everyone

Kymriah is only for children and young adults up to age 20 who have B-cell ALL that has not responded to standard treatments or that has relapsed at least twice. Most children with B-cell ALL respond to standard treatment and do not relapse.

“Some parents don’t understand why new drugs with exciting, promising results aren’t for their kids. Who can blame them? All parents want the best care for their child,” says Amy Sherrod, RN, MSN, CPNP, who is director of cancer information at the American Cancer Society. As a nurse practitioner in pediatric oncology, Sherrod has had hands-on experience treating kids with cancer.

“Sometimes we have to explain to parents and patients that the best possible treatment isn’t the newest one. It could be harmful to give a child such a new drug, one that we’re still studying, when most children have a strong chance of cure with treatments that have had many years of research,” Sherrod explains.

Future goals

“We’re inching our way to making a huge difference. We’ve gone 100 feet, not a mile, but that 100 feet means something. A group of kids with relapsed or refractory ALL who may have died 10 years ago, have a chance today with immunotherapy,” says Sherrod. More research is needed, and she's excited about what else is in the works.

For example, some researchers are looking for ways to make immunotherapies better at recognizing and destroying leukemia cells. And others are trying to figure out how to get gene therapy to work in solid tumors, which has so far been much more challenging.

Future articles in this series will explore these emerging areas of immunotherapy for children with cancer.