Pediatric Immunotherapy: What’s Next for CAR-T Therapy

On Aug. 30, 2017, the U.S. Food and Drug Administration approved the use of chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). As the first-ever cell therapy to win FDA approval, Kymriah™ (tisagenlecleucel, Novartis) is a CD19-targeted CAR-T therapy, and this approval is the result of five years of clinical trials supervised by lead investigator Stephan Grupp, MD, PhD, Director of the Cancer Immunotherapy Program at Children’s Hospital of Philadelphia (CHOP).

The FDA approval of Kymriah has shifted the paradigm for pediatric cancer treatment — and at CHOP, more cell therapies are on the horizon.

At Children’s Hospital, Shannon Maude, MD, PhD, is conducting a pilot study to evaluate an alternative, humanized CD19 CAR-T product, referred to as huCART19 or CTL119. This CAR is being studied for retreatment in patients with CD19+ leukemia or lymphoma that was previously treated with cell therapy, as well as first CAR therapy for relapsed ALL.

CHOP’s immunotherapy team has been leading the development of a trial testing Kymriah as part of first-line therapy. This study will be run in multiple centers through the Children’s Oncology Group. Here, the focus will be on patients with high-risk disease, with an event-free survival at half or less for children with standard-risk ALL. The trial will test whether cell therapy can prevent relapse and/or the subsequent need for bone marrow transplant in these children with treatment-resistant ALL. A study of this approach is planned to open in the next few months.

In addition, CHOP is designing trials to define other ALL populations that may benefit from CD19 CAR therapy, such as central nervous system (CNS) ALL and patients with Down syndrome, among others.

Kymriah is the result of reprogramming the patient’s own T cells to locate and kill cells that have a protein called CD19 on their surface. But sometimes the leukemia cells don’t have CD19. Such cells can remain hidden from Kymriah and then may multiply, causing a relapse. A research goal is to identify second targets on ALL that can be targeted along with the CD19. One such target, CD22, is currently being tested and will be deployed in combination with a CD19 CAR next year.

Researchers are also working on developing new therapies that reprogram a patient’s own immune system cells to kill other types of cancer besides blood cancers. So far, solid tumors have generally resisted CAR-T cells. For patients with unresectable, metastatic or recurrent synovial sarcoma — a rare form of soft tissue cancer — CHOP is participating in trials testing a different kind of engineered T cell, referred to as a TCR engineered T cells. CAR-T cells are being developed for another pediatric cancer, neuroblastoma. In addition, the possibility is being explored that solid tumors will respond to CAR-T therapies when they are combined with another agent intended to boost T cell function.

With all these promising avenues of investigation, Children’s Hospital of Philadelphia is on the verge of the next breakthrough in immunotherapy to treat the toughest pediatric cancers. For more information about cancer immunotherapy options at CHOP, call 267-426-0762 or contact an intake coordinator online.