As CAR-T immunotherapy grows, pediatric cancer patients could benefit

September 16, 2015 | by Mandy Qualls

Acute lymphoblastic leukemia is the most common type of childhood cancer, accounting for about 30 percent of all pediatric cancers. The disease is characterized by bone or joint pain, fatigue and weight loss, among other symptoms. Although it can be very aggressive, it's also considered highly treatable. Soon it may become more so.

Because most patients with the disease have cells that carry a protein called CD19, they’re poised to benefit from one of the most exciting forms of therapy increasingly available to cancer patients: a form of immunotherapy known as CAR-T therapy.

Though still in the early stages of development, CAR-T therapy shows great potential because it’s individualized to each patient. The T in CAR-T stands for T cells, a type of white blood cell that seeks out and destroys invading cells and foreign objects, and the CAR stands for chimeric antigen receptors, which are proteins that allow the T cells to recognize a specific protein on tumor cells.{C}

To create the therapy, physicians and researchers remove T cells from a patient’s blood, modifying them to kill the patient’s specific cancerous cells, and inject the T cells back into the body. The process involves the manufacturing of a receptor for tumor proteins that is inserted onto the T cells.

“Instead of invading the entire body with heavy doses of chemotherapy and radiation therapy, we will take the patient’s own immune cells and retrain them to attack leukemia cells,” said Joseph Rosenthal, M.D., the Barron Hilton Chair in Pediatrics and chief of the Division of Pediatric Hematology/Oncology at City of Hope.

Getting the therapy ready for prime-time

One issue yet to be resolved, Rosenthal acknowledged, is patient side effects. When the reengineered T cells destroy the leukemia cells, the contents of the dead cells spill into the bloodstream. This triggers a high-level immune activation in the body called a cytokine release storm (CRS).

“The patient, during this short period of time, is exposed to very large concentrations of agents usually used in the normal inflammatory process,” said Rosenthal. “The patient may develop hypertension, respiratory distress and fluid overload. It’s really a life-threatening condition.”

Still, the therapy has enormous potential.

“Our long-term vision is that we will have more than one tool that will enable us to eradicate leukemia in more patients for a longer time with less devastating effects from the treatment,” said Rosenthal. “The patients who have been treated with CAR-T cells at this point are mostly patients who have already had bone marrow transplants and did not have any other options.”

When it comes to pediatric cancers, the treatment has been used only for children with what's known as pre-B acute lymphocytic leukemia, Rosenthal said.

He and other researchers hope that, at some point, the treatment will “move to the front lines,” so that if a patient has suffered a relapse of leukemia, CAR-T therapy will be a viable and readily available treatment.

One obstacle researchers at City of Hope already ave overcome is keeping CAR-T cells alive long enough to destroy all leukemia cells. In early clinical trials, the engineered CAR-T cells would not survive to kill off the leukemia. Now, the CAR-T cells live far longer, which Rosenthal says is the most encouraging part of overcoming this obstacle.

Closer to reality for more patients

City of Hope is currently conducting clinical trials using CAR-T cells and plans to soon launch new trials. Rosenthal hopes to find out if CAR-T therapy can be applied to solid tumors as well as leukemia, as solid tumors are far more common. CAR-T therapy research for cancers other than leukemia is still in the preclinical phase.

Researchers at City of Hope know the long-term impacts of stem cell transplantation because they follow thousands of patients who experience the procedure to treat their leukemia. But they don’t yet know the lasting effects of CAR-T therapy.

“The justification is and has been that in order to save a life, you pay a heavy price in health terms,” said Rosenthal. “Could you minimize that cost by using CAR-T cells? I believe this question will be answered in the near future.”

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Learn more about becoming a patient or getting a second opinion at City of Hope by visiting our website or by calling 800-826-HOPE (4673). You may also request a new patient appointment online. City of Hope staff will explain what's required for a consult at City of Hope and help you determine, before you come in, whether or not your insurance will pay for the appointment.

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