Ashley Plant-Fox, MD is an attending physician in hematology, oncology, neuro-oncology and stem cell transplantation at Ann & Robert H. Lurie Children’s Hospital of Chicago. She is also an associate professor at Northwestern University Feinberg School of Medicine.
Dr. Plant-Fox’s goal as a physician is to help improve outcomes in pediatric cancer patients diagnosed with brain tumors. The focus of her work is on translational research and early clinical trial development for pediatric neuro-oncology.
Pediatric brain tumors are the second most common form of cancer in children and the number one cause of cancer-related mortality in childhood. Diffuse intrinsic pontine glioma (DIPG) is a particularly rare and aggressive form of pediatric brain cancer typically found in children ages 5-8 years, with around 200-300 children being diagnosed annually. Symptom onset in patients with DIPG is rapid, occurring in just a few weeks. Common symptoms include the inability to walk, the inability to swallow, headaches, nausea and vomiting, abnormal eye movements, lethargy, and more.
There is currently no treatment for DIPG, with most children receiving palliative radiation therapy to alleviate their symptoms. DIPG tumors typically progress around 6-9 months after radiation therapy, with most patients succumbing to the disease within 12 months of initial diagnosis. At the moment, there is a less than 1% five-year survival rate for patients with DIPG.
Little was known about this disease until a group of parents of children diagnosed with DIPG allowed researchers to attempt safe biopsy of the pons, the area of the brainstem where DIPG tumors form. The results showed that 80% of DIPG tumors harbor genetic mutations in histone proteins, which package DNA into nucleosomes and are involved in positive and negative regulation of transcription, the process of DNA being copied into RNA. The role of histones in regulating gene expression makes these mutations difficult to target.
One possible mechanism for targeting DIPG’s known mutations is immunotherapy, an approach to cancer therapy that uses the body’s own immune system against the tumor.
For her work in developing a vaccine for the treatment of DIPG, the Pediatric Cancer Research Foundation has funded Dr. Plant-Fox since 2019 via the Will Irwin Fund Designated Grant. She also received support from the Audrey Coon Fund Designated Grant in 2021.
The goal of Dr. Plant-Fox’s vaccine, called rHSC-DIPGVax, is to help patients’ immune systems recognize the genetic alterations known to be present in DIPG tumors and to incite the body’s T cells to combat the tumor. The vaccine uses recombinant heat shock proteins that can interact with both the innate and adaptive immune systems to present 16 tumor markers, including markers of the histone protein mutations and other secondary mutations found in DIPG. Dr. Plant-Fox will also combine this vaccine therapy with two other molecules called checkpoint blockade molecules, Balstilimab and Zalifrelimab, to further expand the immune response.
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