powering cures, realizing futures


Ashley Plant

Dr. Ashley Plant-Fox
Designated Grant

Ann & Robert H. Lurie Children’s Hospital

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Thanks to the Will Irwin Memorial Fund, PCRF is proud to support the leading-edge DIPG research of Dr. Plant at Lurie Children’s Hospital of Chicago.

“Pediatric brain tumors represent the second most common cancer type in children and are the number one cause of cancer-related mortality in childhood. Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer that is typically found in children ages 5-8 years and has rapid onset of symptoms over a period of weeks. There are around 200-300 children per year diagnosed with this disease.  Symptoms include inability to walk, inability to swallow, headache, nausea/vomiting, abnormal eye movements, lethargy, etc. There is no treatment available for this tumor although most children receive palliative radiation therapy to improve their symptoms. Families travel across the country and sometimes the world seeking available clinical trials or new treatments. Typically, these tumors progress around six to nine months after radiation therapy and most will succumb to their disease by 12 months from diagnosis. There is a less than 1% overall survival at 5 years.

Little was known about DIPG up until a group of heroic parents of children with DIPG allowed researchers to attempt safe biopsy of the pons, an area of the brainstem, to further elucidate the molecular characteristics of these devastating tumors. Through this work it was found that 80% of these tumors harbor genetic mutations in histone proteins, specifically K27M H3.3 or K27M H3.1. These mutations also predictably occur with secondary genetic aberrations, such as, K27M H3.3 with PDGFRA amplifications and K27M H3.1 with ACVR1 mutations. Histone proteins package DNA into nucleosomes and are involved in positive and negative regulation of transcription, the process of DNA being copied into RNA. Their role in regulating gene expression makes these histone mutations difficult to target. One possible mechanism to target these known mutations is to use immunotherapy, therapy that uses the body’s own immune system to attack the tumor. Here, we have created a vaccine, rHSC-DIPGVax, with the goal of triggering the immune system to recognize the genetic alterations known to be present in DIPG tumors and, using immune cells known as T cells, attack the tumor. This vaccine will use 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 and, hopefully, incite an immune response. We will also combine this vaccine therapy with two other molecules called a checkpoint blockade molecules, AGEN2034 and AGEN1884, to further expand the immune response. This combination immunotherapy for the treatment of newly diagnosed DIPG and diffuse midline glioma will move forward in a phase I/II clinical trial later this year.

Thank you to the Irwin Family and the Pediatric Cancer Research Foundation (PCRF) for their support of this research. We would not be able to move this project forward for this rare and devastating disease without the support from families and foundations like yours.” -Dr. Ashley Plant

*If you would like further details or information on Dr. Plant’s work or the Will Irwin Fund, please contact Jeri Wilson at jwilson@pcrf-kids.org

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