The Ty Louis Campbell Fellowship – Precision Medicine

Weill Cornell Medicine

In 2014, The TLC Foundation announced the launch of a new pediatric brain tumor research fellowship at the Weill Cornell Medicine Children’s Brain Tumor Project.

Led by Co-Directors Dr. Mark Souweidane and Dr. Jeffrey Greenfield, The Children’s Brain Tumor Project shares our mission to improve the outcome for children with brain tumors by advancing scientific discovery and clinical research.  The Ty Louis Campbell Fellowship is an ongoing annual grant of $65,000 to support Dr. Jeffrey Greenfield’s research in precision medicine by providing the funding for a dedicated neuro-scientist working in the lab.

TLC is proud to report the renewal of the three-year fellowship through 2020.

2016 – 2020: To read recent peer-reviewed publications that were authored by the current Ty Louis Campbell Fellow, Carolina Cocito, visit this link to PUBMED.

2014 – 2015: To read peer-reviewed publications that were authored by the previous Ty Louis Campbell Fellow, Sheng Li, visit this link to PUBMED.

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Gift from a Child – Tissue Navigators

In partnership with the Swifty Foundation.

The Ty Louis Campbell Foundation is proud to support the Gift from a Child initiative with a pledge of $75,000 over three years. Our support helps to fund a “tissue navigator” at designated centers of excellence across the US, including Stanford, Children’s Hospital of Philadelphia, Lurie Children’s Hospital, Children’s National and Weill Cornell Medicine. Centers of Excellence are regional autopsy sites designated to coordinate, process, store, and share post-mortem materials that enable research across institutions and increase information sharing.

Tragically, thousands of children die from brain tumors every year. Researchers and physicians do not know why the treatments do not work for these children. Until researchers are able to study the brain tissue of children who do not survive their cancer, it will remain a mystery why these children do not survive their disease. More so, it leaves the clinical team in the dark when treating new patients facing similar outcomes.

The Gift from a Child program addresses this need by facilitating the collection of a critical mass of brain tumor tissue samples to inform scientists on how tumors behave and how to prevent them from forming. Understanding more about each unique tumor type allows doctors to prescribe specific treatments for each individual child. This helps to minimize the harmful side effects of many treatments that are currently available, and increases the quality of life for children diagnosed with these diseases.

The Tissue Navigator is an individual who will educate patients, families, and staff about the value of tissue donation, assist patients and families with the logistics related to making such a donation at the time of a child’s death, and coordinate tissue donations from other local and regional centers that don’t have formal donation programs in place.

Without collaborative systems like this in place, and dedicated individuals serving as tissue navigators at each regional site, these precious donations are not be possible.

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Intrinsic and Acquired Glucocorticoid Resistance in T-cell ALL

University of San Francisco – In Partnership with the St. Baldrick’s Foundation

$195,000 over two years.

Acute Lymphoblastic Leukemia (ALL) is the most common form of childhood cancer. Thanks to decades of scientific research, most children diagnosed with ALL in 2020 are curable. However, children who suffer recurrent leukemia after an initial response to therapy become very difficult to treat, and many do not survive in the long-term.

Anya Levinson, a clinical fellow in pediatrics at University of California, San Francisco, studies the role of “glucocorticoids” (a type of steroid) in the treatment of T-cell ALL. Though glucocorticoids are usually very effective at killing leukemia cells, some patients are found to be resistant to glucocorticoids, making their disease more difficult to treat.

Levinson’s research is focused on understanding how and why such resistance develops in order to identify ways to overcome it and, ultimately, increase survivorship for children with T-cell ALL by preventing and/or successfully treating relapse. Levinson is focused on two emerging glucocorticoid resistance mechanisms called JDP2 and STAT5B.

The overarching goal of Levinson’s research project is to further characterize the molecular mechanisms in these pathways to identify therapeutic agents to mitigate glucocoricoid resistance. Specifically, to 1) determine the molecular basis of JDP2-induced glucocorticoid resistance and test for ways to overcome it, and 2) determine whether ruxolitinib or the BCL-2 inhibitor venetoclax can overcome GC resistance conferred by the expression of mutant alleles of components of the IL7R/JAK/STAT pathway.

READ MORE IN THIS THOUGHTFUL Q&A WITH DR. LEVINSON

This research is funded in part by the Westlake Wildcats “Spirit Day” initiatives in loving memory of Danny Mcmanus.  Danny was a courageous young athlete from Armonk, NY, who passed away from relapsed Leukemia at the age of 12.  

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Combination anti-CD47 Immunotherapy

Stanford University School of Medicine and Huntsman Research Institute, Salt Lake City

The Ty Louis Campbell Foundation partnered with the St. Baldrick’s Foundation and awarded funding for a three-year pre-clinical research project to Dr. Samuel Cheshier, Stanford University, totaling $330,000, with additional seed money ($15,000) provided to help kick off a phase 1 clinical trial after the pre-clinical results proved so promising.  The clinical trial is expected to enroll patients in 2020.

Dr. Cheshier’s work utilizes combinations of immune therapies to target malignant pediatric brain tumors. These treatments allow the immune system cells called macrophages to specifically target and “eat” the cancer cells while leaving normal tissues unharmed. The research goal is to develop these treatments in order to replace chemotherapy and irradiation, which are less specific to the cancer and more harmful to the patients than his proposed immune therapies.

The study focuses on combination therapies using antibodies called anti-CD47 and anti-CD40. When utilized in combination in mouse models, there was significant synergistic effect when compared to utilizing either agent alone.

In March 2017, results were reported in various medical journals. Read moreA report was also published in the Wiley Online Library (April 2016) citing some of the resulting work from this study pertaining to glioblastoma. Read more.

A 2016 update report on the research progress can be downloaded here.

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Checkpoint Inhibitors – Phase 2 International Clinical Trial

Multiple Centers (originally led by Memorial Sloan Kettering Cancer Center)

What began as a proposal for a clinical trial in four centers, has expanded into a worldwide clinical trial.

In 2016, the TLC Foundation, in collaboration with like-minded nonprofits A Kids’ Brain Tumor Cure and Solving Kids’ Cancer, provided the seed money for a phase 1 clinical trial for children with brain tumors using combination immunotherapy that targets controlling factors in the body’s immune system called checkpoints for a total investment of $185,000.

What began as a proposal for a four center US-based clinical trial of a promising combination therapy for children battling brain tumors, quickly expanded into a large-scale phase 2 clinical trial at 58 centers in 13 countries, bringing new hope to children across the globe who have run out of treatment options.

This collaborative funding model and potential impact of the new therapy attracted the attention of pharmaceutical giant Bristol Myers-Squibb, and led to a major expansion of the project into the International Phase 2 clinical trial that just completed enrollment in 2019, and is now in the process of analyzing the data with the goal of presenting the findings before the end of the year.

Checkpoint inhibitors are therapeutic antibodies that block the inhibitory receptor signaling and restore the capacity of T-cells to kill cancer. The trial targeted two types of checkpoint receptors – (PD1 and CTLA4) using a combination of antibodies that targeted the immune system rather than the cancer itself. Checkpoint combination therapy has been the most exciting breakthrough in cancer research this decade. Adults with previously untreatable cancers like metastatic melanoma and lung cancer have been cured in clinical trials.

Had it not been for these three nonprofits trusting in this idea, this clinical trial may have never come to fruition. By working together, nonprofits and medical institutions can move the needle forward faster. An update report from January 2019 can be found here. Information on the trial can also be found at clinicaltrials.gov.

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Collaborative Research Funding for Relapsed and Refractory Pediatric Brain Tumors offers Hope

Memorial Sloan Kettering Cancer Center (with 11 additional treatment sites)

After co-funding a highly successful international clinical trial that opened for international enrollment in 2017, A Kids’ Brain Tumor Cure Foundation, Solving Kids’ Cancer and the Ty Louis Campbell (TLC) Foundation have teamed up again to announce their joint financial support of a Phase 1 clinical trial that will test the safety and efficacy of a new immunotherapy produced by Apexigen to treat of children with brain tumors.   

The study will test safety and efficacy of a promising new agent, APX-005M CD40, against antibodies in children with brain tumors.  This first-in-class immunotherapy has the potential for significant efficacy in children with recurrent or refractory tumors in the central nervous system, and it is a new therapy option for children with newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG), a type of brain cancer that is 100% terminal upon diagnosis. It has been rolled out via the Pediatric Brain Tumor Consortium (PBTC), a collective group of multidisciplinary research organizations, which allows more children access to this promising new treatment option in twelve reputable institutions across the country.  

This is the second immunotherapy trial being funded by these three like-minded nonprofits as a result of their mutual support of primary investigator, Dr. Ira Dunkel, Memorial Sloan Kettering Cancer Center, and their confidence in multi-faceted collaborative efforts as a progressive way forward.  The clinical trial is currently open for enrollment, and more information can be found here on clinicaltrials.gov

“Collaboration is the driving force behind making progress in research, faster,” said Dr. Ira Dunkel, Memorial Sloan Kettering Cancer Center.  “Similar to the efforts of nonprofit organizations that have been partnering for years to increase their impact, a team of researchers founded the Pediatric Brain Tumor Consortium in 1999 to advance progress through multi-center, multidisciplinary, innovative studies with designs and analyses based on its shared high standard of statistical science.”

Dr. Dunkel’s most recently shared that trial accrual is going well and taking place in a timely fashion, hoping to complete the non-DIPG accruals by mid-2019 (which can often be a challenge in other pediatric brain tumor trials).  The dosing levels have been increased three times, and it is predicted that the DIPG arm will start based on the dose findings from the non-DIPG participants.

Collectively, these three like-minded nonprofits made a contribution of $120,000 to help make this trial available to children battling brain tumors, today. It is currently open for enrollment, providing a viable option with far less toxicity than chemotherapy to children in need of alternative options.  

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Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT

University of San Francisco

Oncolytic viruses (OVs) are promising therapeutic tools for solid tumors due to their many biological advantages compared to traditional approaches including: (1) the selective replication of the OVs in cancer cells without affecting normal cells; (2) the lack of resistance mechanism by the targeted cells and (3) the capacity of the OV to spread throughout the tumor once a few cells have been infected (4) the capacity to trigger an immune response against the tumors. These protocols represent a potential therapy for several tumors, including rare pediatric brain tumors, due to their capacity to target cancer stem cells (CSC) which are, in theory, the cells responsible for tumor growth.

Dr. Sabine Mueller kicked off a phase 1 clinical trial using the measles virus (MV-NIS) and after seeing promise in the pre-clinical findings, the Ty Louis Campbell Foundation provided additional funding to support her continued research on this particular trial, and we hope to see enrollment expand over the next year or so.  Enrollment remains ongoing, therefore results have yet to be published.  Information about the ongoing clinical trial can be found at clinicaltrials.gov.

View the most recent update provided by our co-funding partners at Solving Kids’ Cancer here: TLC Project MVNIS Update Jan 2019 (2).

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Patient Specific Organotypic Tumor Platform for Treatment Selection in Embryonic Tumors – HR Medulloblastoma, AT/RT, ETMR

Columbia University Medical Center

In collaboration with several like-minded nonprofits, the Ty Louis Campbell Foundation is supporting the work of Dr. Stergios Zacharoulis as he researches the unique molecular fingerprints of embryonal tumors found in pediatric patients, including medulloblastoma, AT/RT and ETMR. These research advancements may lay the foundation for developing new treatment protocols for high risk pediatric brain tumors.

Organotypic cultures, or “slices,” represent an in vitro model that simulates the in vivo situation very well. In other words, scientists can study the organotypic tumor tissue in the same way they might study tumor behavior in an avatar (mouse) model, but the process is much faster.  Dr. Zacharoulis is using high quality slices of pediatric brain tumor tissue to assess the potential of novel substances that may be effective in killing tumor tissue, in addition to better understanding the biological behavior of the tumor cells.  For embryonal tumors, including rare sub-types of medulloblastoma, AT/RT and ETMR, there is a tremendous need for increased tumor analysis to better understand what his happening at the molecular level.

This project requires just a small cohort of patient participants to prove safety and expand access. The strategic priority of this project is ultimately impact frontline, relapse and maintenance therapy with promising new modalities.  

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Targeting Proteins CDK 7, 12, 13 against Ewing Sarcoma 

Dana-Farber Cancer Institute

Ewing sarcoma is a bone cancer that is most frequently found in children and adolescents between the ages of 10 and 20 years old.  Tumors often originate in the long, large bones of the body, including the hip, thigh, shin, chest, and arm bones.

Besides originating from the bone, sometimes this tumor can form just outside the bone in the soft tissue.  The cancer can also metastasize to other sites including the lungs, other bones or soft tissue areas, and bone marrow, making the disease more difficult to treat and resulting in significantly lower survival rates.

At the Ty Louis Campbell Foundation, we support the groundbreaking work of Dr. Kimberly Stegmaier at Dana-Farber Cancer Institute to help find a cure for this disease.  In 2016, TLC first provided financial support to help bring new targeted therapies to patients battling Ewing Sarcoma, and we have since designated her lab as the beneficiary of our fundraising events in Massachusetts to honor a local survivor of Ewing Sarcoma named Carly (the annual “Rockin’ for a Reason” concert, in particular).

Dr. Stegmaier’s team has identified a new drug class that is highly active in Ewing sarcoma cells, targeting proteins called CDK 7, 12, and 13. These proteins are important in the expression of genes in the cell and also in the control of DNA damage.  To learn more about how the team intends to bring these breakthroughs to clinic, click here.

In December 2019, a team of students toured the lab with Dr. Stegmaier, and presented her with another $5,000 to support the continuation of her progressive work in both Ewing Sarcoma and Neuroblastoma.  The funding resulted from the 2018 and 2019 “Rockin’ for a Reason” concerts in Upton, MA.

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Convection-Enhanced Delivery for DIPG

Weill Cornell Medicine

photo credit: Humans of New York

Diffuse intrinsic pontine glioma (DIPG) is one of the deadliest central nervous system tumors of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimizing systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma.

TLC has been supporting the efforts of Dr. Mark Souweidane since 2018 to expand on his existing Phase 1 trial, which has been referred to as groundbreaking by the Lancet Oncology. The peer-reviewed publication in the Lancet validates a career-long hypothesis that Dr. Souweidane put forth more than 20 years ago, and was only made possible by the families who entrusted their children in his care by enrolling in the trial, and the donors who have provided the financial support to enable this research (read his inspiring blog here).

The results are so promising, they are expected to eventually change the landscape of future pediatric brain tumor protocols.   

View the article abstract here.

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International Rhabdoid Conference 2018

Lake Louise, Alberta Canada.international rhabdoid tumor meeting 2018

The TLC Foundation made a unique investment by supporting the 2018 International Rhabdoid Tumor Meeting in Lake Louise. Eighty-eight scientists from around the world gathered for a 2-day conference on rhabdoid tumors, with most of the focus being on Atypical Teratoid Rhabdoid Tumors (AT/RT).  AT/RT is a rare pediatric brain tumor that claimed the life of Ty Louis Campbell, and that has been widely neglected by the research community until now.

There is a common phrase, “you don’t know what you don’t know” that certainly rings true in the research community.  Information sharing is imperative to advancing research.  This “meeting of the minds” was a tremendous accomplishment for advancing discoveries in ATRT.  The collaborative group worked together to develop a classification system for ATRT’s that can be used in all clinical trials, and TLC was in attendance to see the breakthrough results presented from the anti-CD47 research we also supported.

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Collaborative Advocacy Initiative Addressing Medulloblastoma, ETMR and AT/RT

In Partnership with Solving Kids’ Cancer

Our partners at Solving Kids’ Cancer have long been advocating to influence clinical trial design. With the support of TLC, they have launched a strategic initiative that will help identify the projects that can be added to frontline treatments quickly and effectively through the creation of small pilot studies intended to produce actionable data.  By securing partners in collaborative groups and consortiums, the initiative is addressing the issue that there are currently too many possibilities for too few patients.  In support of this initiatives, TLC is part of the conversation among a core group of top investigators across the country who are engaged in the design and implementation of this innovative strategy.