ACGT funding leads to CAR T-cell breakthrough for pediatric cancers

May 16, 2022
Devin Golden

Crystal Mackall, MD

Some of the most promising clinical research in cancer cell and gene therapy for solid tumors and specifically brain tumors, is happening at Stanford University – led by Crystal Mackall, MD, a member of the Alliance for Cancer Gene Therapy’s Scientific Advisory Council and an ACGT Research Fellow.

Dr. Mackall, the founding director of the Stanford Center for Cell Therapy, applied grant funding from Alliance for Cancer Gene Therapy to develop GD2-targeting CAR T cells.

These CAR T cells are now being studied in clinical trials for a devastating brain cancer called diffuse intrinsic pontine glioma (DIPG).

The phase 1 trial showcases the potential of cancer cell and gene therapy for solid tumors – with adjustments to the therapies created for blood cancers such as leukemia and lymphoma.

Dr. Mackall and her team presented the findings of this phase 1 trial at the American Association for Cancer Research (AACR) meeting in New Orleans in April. They received a standing ovation for the early results.

What Is DIPG?

DIPG is a cancer of the brainstem, which is the lowest part of the brain and connects the organ and spinal cord. It mostly affects children, who make up most of the participants in Dr. Mackall’s clinical trial.

According to the Dana-Farber Cancer Institute, DIPG accounts for around 10% of all pediatric central nervous system cancers.

Close to 300 children are diagnosed in the United States each year.

The symptoms of DIPG include:

  • Issues controlling eye movement, facial expressions, speech, chewing and swallowing 
  • Weak arms and legs
  • Problems with walking and coordination

Radiation therapy and chemotherapy are the two standard options for DIPG treatment. Surgery is not  an option due to the tumor’s location in the brainstem.

CAR T cells lead to survival milestones for patients

The average life expectancy for this cancer – along with another brain cancer, glioblastoma – is just a few months. However, some patients in the Stanford University trial are doubling and even tripling the standard survival timelines.

The results are so extraordinary that USA Today published an article featuring the study – along with telling the stories of a few patients enrolled. One of the patients, 5-year-old Mary Stegmueller, is alive approximately one year since her diagnosis.

As of April, when the study was presented during the AACR annual meeting:

  • A total of four patients continue to receive new CAR T cells between seven and 12 months after enrolling in the trial
  • Some participants have had a near-complete disease response – tumor volume shrunk by at least 95%
  • One case had tumor volume shrink 98%

There are two noteworthy elements of the study: number of cycles of CAR T-cell treatment; and method of administration. For blood cancers, patients receive one infusion of CAR T cells. Dr. Mackall and her team discovered that repeated treatments can help for glioma.

Additionally, they tested administering through an IV – similar to the process for blood cancers – and with an intracerebroventricular (ICV) delivery. The latter method sends CAR T cells directly to the brain rather than through the bloodstream.

The results show patients were less likely to experience cytokine release syndrome from ICV delivery. Cytokine release syndrome is one of the main side effects of CAR T-cell therapy, defined as a release of cytokine proteins from an overstimulated immune system.

The phase 1 trial is accepting up to 54 patients. Stanford University and Dr. Mackall will open a second arm of the study in preparation for a phase 2 trial.

ACGT’s alliance with Dr. Mackall and other researchers

Aside from being the founding director of Stanford University’s Center for Cancer Cell Therapy, Dr. Mackall is associate director of the Stanford Cancer Institute. Those two titles are evidence of her expertise in cell and gene therapy for cancer.

Dr. Mackall also earned an Alliance for Cancer Gene Therapy grant in 2016 centered around her GD2 research. She originally was investigating the biomarker and CAR T-cell target for pediatric neuroblastoma and sarcoma but discovered GD2 is also expressed on pediatric DIPG.

Alliance for Cancer Gene Therapy’s funding has created new therapeutic opportunities and hope for both neuroblastoma and sarcoma and the deadly childhood brain cancer, DIPG. ACGT continues to fund innovative research projects led by the brightest scientific minds in the world. Please donate to Alliance for Gene Therapy as a way of supporting scientists like Dr. Mackall.

You can read more about the DIPG clinical trial here and the osteosarcoma and neuroblastoma study here.

Page sources

  1. CT001 – Major tumor regressions in H3K27M-mutated diffuse midline glioma (DMG) following sequential intravenous (IV) and intracerebroventricular (ICV) delivery of GD2-CAR T cells. Abstracts Online. Retrieved from:!/10517/presentation/20143. Accessed: 04/12/2022.
  2. Revolutionary leukemia treatment offers ‘a hopeful moment’ in fight against solid tumors. USA Today. Retrieved from: Accessed: 04/12/2022.
  3. Childhood Diffuse Intrinsic Pontine Glioma. Dana-Farber Cancer Institute. Retrieved from: Accessed: 04/12/2022.