ChadTough Defeat DIPG Foundation funds the most promising childhood brain cancer research across the globe. To date, the foundation, along with their partners and donors, has funded over 75 researchers, across 39 institutions, totaling over $29 million.
CAR T-cell therapy has shown success in treating certain types of cancer in children. This therapy trains the immune system’s T cells to locate and eliminate cancer cells. However, until recently, CAR T-cell therapy was not available for children with brain tumors like DIPG. In 2021, Stanford doctors, including Dr. Ramakrishna, initiated a clinical trial to use CAR T-cells for treating DIPG in children and young adults. Encouragingly, 10 out of 12 patients who received these CAR T-cells experienced tumor shrinkage and improvement in symptoms. This project aims to gain insights from patients to understand why CAR T-cell therapy succeeded or failed, with the aim of enhancing and optimizing the treatment.
In all cancers, certain genes become overactive to fuel their growth and aggressiveness. To function properly, genes need to convert their DNA code into a temporary form called RNA, which serves as a template for producing proteins that carry out cellular functions. In DIPG, many of the genes responsible for cell growth disrupt the normal process of RNA translation, leading to the production of unintended protein products. Through this project, Dr. Prensner proposes that targeting this abnormal RNA processing could be a vulnerability in DIPG that can be exploited for treatment. This research will be the first systematic exploration of this abnormal RNA translation in DIPG and will link it to different known genes involved in driving the disease.
This project aims to develop a powerful and innovative immunotherapy using induced pluripotent stem cell (iPSC)-derived NK cells. These engineered NK cells aim to eliminate DIPG and enhance the activity of other immune cells against the tumor. Dr. Matosevic intends to demonstrate that combining iPSC-engineered NK cells with strategies to disrupt the DIPG TME will challenge current treatment approaches and revolutionize the way we treat DIPG.
Dr. Ligon and his team have developed a new treatment called RNA nanoparticle vaccines (RNA-NPs) to combat DIPG and other cancers. These personalized vaccines stimulate the body’s immune system to recognize and eliminate cancer cells. The treatment has shown promise in clinical trials for adult brain cancer patients, and now they plan to extend the trials to children with a different type of brain cancer, as well as patients with melanoma (skin cancer) and osteosarcoma (bone cancer). Encouraging initial results suggest that RNA-NPs could also be effective against DIPG. This project aims to further investigate the potential of RNA-NPs for treating children with DIPG and gain a better understanding of their effectiveness across various cancer types.
DMG is characterized by a specific mutation called H3K27M. This mutation affects a group of proteins known as polycomb repressive complexes 2 (PRC2), which play a vital role in determining cell development. The goal of this project is to gain a deeper understanding of PRC2’s role in the normal development of the pons, a critical part of the brain. Specifically, Dr. Keane will study cells with increased PRC2 activity and examine their DNA to identify any changes that occur when PRC2 activity is heightened. Additionally, she will investigate the presence and role of immune cells in the pons during this crucial time, examining how they contribute to the growth and expansion of this vulnerable region.
DMGs are brain tumors that often spread diffusely, making it challenging to track their progression. Current methods rely heavily on MRI scans, which do not always provide accurate information about treatment response. Dr. Viswanath and Dr. Mueller have discovered that changes in deuterated glucose metabolism can be observed within five days of radiotherapy in mice with DMGs, even when MRI scans show no visible alterations. In this study, they aim to investigate whether deuterated glucose can be used to visualize active tumor tissue and serve as an early indicator of therapy response in DMG-bearing mice.
New research has shown that 80% of DMG cases exhibit high levels of a protein called GD2. To target GD2, scientists are utilizing immunotherapy to destroy cancer cells. Dr. Omer and his team have improved the effectiveness of the GD2-targeting CAR T-cells by incorporating an additional gene, C7R, which enhances their anti-tumor capabilities and extends their lifespan. So far, they have treated 12 patients, with two experiencing tumor reduction exceeding 50%. To further enhance the therapy’s effectiveness, they plan to attack the tumor from multiple angles by administering CAR T-cells intravenously and directly into the spinal fluid surrounding the brain and spine.
This project will build on Dr. Majzner’s experience treating children with DIPG with CAR T-cells. Several patients have developed significant responses, however, some showed only temporary improvement or did not respond at all. Through this project, Dr. Majzner and his team aim to test and validate a new type of GD2 CAR T cell that is capable of enhanced persistence and anti-tumor efficacy, providing a more effective strategy for treating patients with DIPG/DMG.
This grant enables the purchase a Beckman-Coulter Optima MAX-XP Tabletop Ultracentrifuge. It is required for the optimized protocol for ribosome profiling for DIPG samples.
Most DIPGs are triggered by a specific genetic event that impacts the way brain cells regulate DNA activity. In effect, DIPG cells begin to awaken parts of the genome that are generally kept quiescent. Some of these genomic regions may produce retroviral elements. Under normal circumstances, these retroviral elements can be toxic when highly active, but DIPG cells appear to utilize, or at least tolerate, the presence of retroviral elements. Understanding which of these genomic elements are specifically activated in DIPG, and which produce proteins, may provide unique insights into how DIPG cells function, leading to opportunities for novel therapeutic approaches in this deadly childhood brain cancer.
Dr. Lu discovered that chaetocin, a substance produced naturally by a fungus, when combined with radiation, has an impressive killing effect on DMG/DIPG cells. This project will test this combination in conjunction with the oral drug ONC201 to discover why they work so well together and what may be needed to make them even more effective in the future.
The objective of Dr. Souweidane’s project is to develop more effective drug delivery methods for DIPG/DMG patients. To accomplish this, he will test various drug combinations and drug delivery techniques to more effectively target DIPG/DMG tumors, while avoiding the toxicities associated with the conventional administration of drug therapies. Dr. Souweidane expects the establishment of this drug-delivery platform will support many cutting-edge therapies and early-stage trials in the fight against DIPG/DMG tumors.
Delivering therapeutics directly to brain tumors safely and effectively has been one of the main limitations for the treatment of DIPG/DMG tumors. Drs. Raju and Becher have recently developed an innovative drug delivery technology that crosses the blood-brain barrier, delivering the drug safely to the site of the tumor. In this study, they will optimize the use of this technology in an effort to improve outcomes for DIPG/DMG patients.
A potential new treatment approach in the fight against DIPG/DMG tumors is to combine radiation therapy with targeted treatments against a specific molecule found in the tumor. However, some subtypes of DIPG appear to be resistant to this method. In this project, Dr. Reitman will carry out experiments to determine why that is so and identify combinations of treatments that could be used to overcome this resistance.
While the nature of mutations in DIPG/DIPG progression is still not fully understood, nerve cell activity is emerging as a critical cause of tumor growth. In this study, Dr. Venkatesh will use molecular biology and neuroscience techniques to better understand the dynamics between neurons and DIPG cells, along with combination treatment strategies to potentially change the way DIPG/DMG tumors are treated.
The objective of this study will be to evaluate the use of drugs that target signaling molecules called CDK. These findings will establish a basis for future clinical trials using these inhibitors as therapies for DIPG/DMG tumors in combination with other drugs. The approach of combining multiple drugs under investigation in clinical trials for DIPG treatment will challenge existing paradigms and provide a basis for the development of drug combinations aimed at achieving complete tumor control.
Dr. Vittorio works with copper chelating agents, which already have wide use in other cancers, to demonstrate the effectiveness of treating brain tumors. This grant will allow his research team to exhibit their expertise in copper biology as they uncover effective drug combinations to reduce copper in DIPG/DMG cancer cells, killing them and improving the survival rate in DIPG/DMG patients.
In addition to the grants made through the structured program, the foundation is excited to continue to support the promising Car T-cell trial led by Dr. Michelle Monje of Stanford University with our new co-funders, Storm the Heavens Fund, the SoSo Strong Pediatric Brain Tumor Foundation and the Elle’s Angels Foundation. The trial has shown great promise and, after decades, could finally offer patients with DIPG/DMG a new treatment option for a disease that has historically proven resistant to other therapies.
ChadTough Defeat DIPG Foundation is a 501(c)(3) nonprofit organization.
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