Yuvaan Tiwari Foundation Advances CAR T Cell Therapy Research for Diffuse Midline Gliomas through Monje Lab

In honor of what would have been Yuvaan (“Yuvi”) Tiwari’s sixth birthday, the Yuvaan Tiwari Foundation is making a gift of $675,000, spread over three years, to the lab of renowned Stanford pediatric brain tumor physician and scientist Michelle Monje, MD, PhD.

Yuvi was a bright, active, and loving 2-year-old who was excited to start preschool. His keen sense of humor brought laughter and smiles to those around him. Sadly, after Yuvi’s parents noticed an abrupt change in his gait and facial features, doctors diagnosed him with diffuse midline glioma (DMG), an aggressive and inoperable pediatric brain tumor. As Yuvi’s mother, Parvati Tiwari, dove into the research surrounding her son’s condition, she came across the Monje Lab at the Stanford School of Medicine.

While today DMG is a universally fatal diagnosis, Dr. Monje’s lab is on a mission to find treatments and a cure. Dr. Monje’s research includes studies into how a child’s own immune cells can be engineered to attack cancer cells. The hope is that these engineered immune cells, known as CAR T cells, can one day serve as a treatment, reducing the size and impact of a patient’s tumor.

“Here at Stanford, we opened one of the first CAR T cell trials for DMG, translating discoveries from the lab to the clinic for children with DMG,” says Dr. Monje. “We have seen promising initial results, but there is so much work to be done to learn how to optimize the treatment and find solutions for all children with DMG. I am so grateful to the Yuvaan Tiwari Foundation for helping us advance this work and learn more about the nuances of CAR T cell therapy as a treatment for children with brain tumors.”

“Through Yuvi’s journey, we witnessed firsthand the urgent need for innovative treatments for DMG. We also discovered the funding gap for research,” says Parvati Tiwari. “Dr. Monje’s groundbreaking work in decoding the biology of DMG and laying the foundation for cancer neuroscience has paved the way for significant advancements in the field. We are optimistic about the application of CAR T-cell therapy, and honored to support the Monje Lab as they continue to optimize immunotherapeutic strategies for DMG, providing a beacon of hope for families in the fight.”

Yuvi passed away in 2021, just seven months after he was diagnosed with DMG. Parvati and her husband, Satya, founded the Yuvaan Tiwari Foundation in his memory. The foundation’s goal is to accelerate innovative pediatric brain tumor research and support impacted families. Since its inception, the foundation has funded over $2 million in DMG research.

“Yuvi always saw the bright side of life and we hope his legacy will continue to shine a light for other children battling brain tumors,” says Parvati.

Yuvaan Tiwari Foundation gifts $1 Million to Koschmann Lab to Accelerate Pediatric Brain Tumor Research

Funds to support an investigative study to bring a targeted EGFR inhibitor into the clinic

The Yuvaan Tiwari Foundation has made a $1 million gift to the Michigan Medicine Chad Carr Pediatric Brain Tumor Center. The gift will support research led by Carl Koschmann, M.D., pediatric neuro-oncologist and researcher at the Rogel Cancer Center and C.S. Mott Children’s Hospital.

Koschmann consulted with Parvati and Satya Tiwari, Yuvi’s parents, early on as they reached out to researchers and physicians across the country to seek potential therapies. Koschmann’s research and treatment of children with high-risk brain tumors, as well as his work with clinical trials that utilize promising medications that kill cancer cells, have uniquely positioned him to drive research of devastating pediatric tumors like DMG.

“From the many doctors we approached during the course of our journey, Dr. Koschmann really stood out,” said Parvati Tiwari, President and Co-Founder of the Yuvaan Tiwari Foundation. “He is an expert in his field, passionate about moving research forward and genuinely cares about every child he treats. The level of progress that is needed may not come from a single lab, and Dr. Koschmann’s collaborative approach will help to further the understanding of DMG and DIPG across institutions globally.”

The gift from the Yuvaan Tiwari Foundation is the largest single donation Koschmann’s lab has ever received. The funding is supporting an investigative study that will attempt to bring into the clinic a drug that targets a protein called EGFR and could offer a treatment opportunity for children with brain tumors. Yuvi’s tumor carried an EGFR genetic mutation, but there was a lack of options in this class of drugs to treat him and other children with this mutation.

“This project is particularly compelling because of my personal connection to the Tiwari family, and because it directly addresses the problem that was brought up in Yuvi’s care,” Koschmann said. “Our team is motivated to move this forward in Yuvi’s memory.”

The promise and potential of discovering an effective EGFR inhibitor that can cross the blood-brain barrier is wider than just tumors with EGFR mutations. Koschmann has treated more than four dozen DMG and diffuse intrinsic pontine glioma (DIPG) patients with an exciting new therapy called ONC201, which targets the energy use, or metabolism, of tumor cells. His group has discovered that many of the DMG and DIPG tumors that didn’t respond to ONC201 had drug resistance driven by the EGFR protein.

Since receiving funding from the Yuvaan Tiwari Foundation, Koschmann’s team has already collected significant amounts of data and partnered with the Dana-Farber Cancer Institute in Boston, gathering dozens of brain tumor samples to send to researchers who are looking at the blood-brain barrier and tumor metabolism. This work will form the basis for a trial combining an EGFR inhibitor with ONC201 in a clinical trial for patients with DMG and DIPG.

“The support from the Yuvaan Tiwari Foundation has enabled our team to push the gas pedal all the way down; the pace of research has really picked up,” Koschmann said. “I have no doubt we will be treating our patients with an EGFR inhibitor within five years. Without the foundation’s support, it would likely be 10 years or never happen.”

Funding for this type of work is often difficult to obtain from large national and government organizations like the National Institutes of Health. Pediatric cancers receive less than 4% of federal cancer research funding, and diseases like DMG and DIPG are granted a small fraction of that amount.

“With more focused research and the brightest minds working on studying DMG together, there is potential to also uncover treatment options for other types of brain tumors as well as other types of cancer” said Parvati Tiwari. “I do believe there’s a cure out there, and we just need to focus more attention and resources on it so we can get there faster. Yuvi left me with the strength and purpose to work toward a future where no family has to go through the pain, hopelessness, and devastation that come with a brain tumor diagnosis.”