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Washington Research Foundation awards $6 million in grants to Fred Hutch Cancer Center and Seattle Children's Research Institute


News provided by

Washington Research Foundation

Oct 22, 2024, 11:59 ET

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Washington Research Foundation
Washington Research Foundation

WRF's new grant program will support development of innovative treatments for cancer and rare immunodeficiency disorder

SEATTLE, Oct. 22, 2024 /PRNewswire-PRWeb/ -- Washington Research Foundation (WRF) has awarded $6 million in grant funding through a new program designed to support late-stage preclinical development and first-in-human clinical trials of novel therapeutics. This program, along with planning grants awarded earlier this year, resulted from WRF's 2023 strategic plan that committed to increasing the foundation's support of large-scale emergent opportunities in life sciences research within the state.

$2 million each has been awarded to teams led by Soheil Meshinchi, M.D., Ph.D., and Aude Chapuis, M.D., both of Fred Hutch Cancer Center (Fred Hutch), and David Rawlings, M.D., of Seattle Children's Research Institute (SCRI). Each is using cutting-edge gene and cell therapy approaches to develop novel therapies in areas of high need.

"These awards recognize that there are promising treatments being pioneered at Washington state research institutions that are so close to benefiting patients." Meher Antia, Ph.D., WRF's director of grant programs

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Meshinchi is developing a treatment for osteosarcoma (OS), a highly aggressive bone cancer that primarily affects children and young adults. Treatments can result in significant side effects, with current interventions including chemotherapy, radiation, and in severe cases, amputation. OS treatments and their outcomes have not significantly improved for nearly 40 years.

Building on earlier work studying a severe form of infant leukemia, Meshinchi found that these leukemia cells had a high density of folate receptor alpha (FOLR1) proteins in their outer membranes. He recognized that this overabundance of surface protein could make these cancer cells a good target for chimeric antigen receptor T-cell (CAR T cell) therapy, an approach in which researchers engineer a patient's own immune cells to identify and eliminate cells that have a specific membrane protein. The team developed a synthetic gene that, when injected into a patient's immune cells, allows them to target cells expressing FOLR1 for elimination. FOLR1 is also highly expressed on the membranes of OS cells, making them suitable targets for the same CAR T-cell approach. In lab tests, these engineered immune cells have been highly effective at killing OS cells. WRF's funding will support additional pre-clinical research and clinical trials for OS.

Chapuis is also engineering T cells to treat cancer. Her team is focused on Merkel cell carcinoma (MCC), an aggressive skin cancer usually caused by the Merkel cell polyomavirus (MCPyV). This virus is commonly found on the skin, but can cause cancer if it infects a cell and integrates its genes into the host cell's genome. Once integrated, the host cell begins producing proteins encoded by the viral DNA that are exclusively expressed in cancerous cells.

Chapuis's research team is genetically engineering T cells to target these viral protein fragments, enabling the precise targeting of MCC cells while leaving healthy cells alone. These engineered T cells both recruit other immune cells to assist in killing identified tumor cells and express a protein that promotes immune function in the tumor microenvironment. This approach has shown great promise in preliminary studies, offering a novel approach to combat MCC. The grant from WRF will support additional construct generation work and an initial clinical study in five patients.

Rawlings and his team at SCRI are developing a treatment for a genetic disorder called X-linked agammaglobulinemia (XLA). Patients with XLA are unable to generate B cells, cannot produce effective antibodies and are highly susceptible to infection. To treat this lifelong illness, patients regularly receive expensive transfusions of pooled antibodies and frequent courses of antibiotics. This treatment still leaves them vulnerable to novel pathogens and ongoing respiratory infections that lead to chronic lung disease as well as other life-threatening complications. Rawlings has been a leader in XLA research for decades and helped to discover the genetic mutation that causes the disorder. Now his team is developing a therapy that could restore a patient's ability to produce functional B cells with just a single treatment.

The Rawlings team has engineered a lentiviral vector capable of integrating a functional copy of the mutated gene into the genome of blood stem cells. To use this technology as a therapy, a patient's own blood stem cells will be collected, treated with the viral vector to incorporate the functional gene, and then reinfused back into the patient. The patient would then be able to produce their own B cells and antibodies. The team's work on this therapy has shown significant potential in mice with the gene mutation underlying XLA and in treatment of stem cells collected from XLA patients. The B cell production of XLA mice and humanized mouse models was restored after being infused with viral-vector transformed mouse and human stem cells, respectively. The WRF funding will help support the completion of vector production, pre-clinical studies and the start of clinical trials.

"There is often a big gap in funding for the hard work leading to the first clinical studies of innovative new therapeutics for relatively rare conditions," said Meher Antia, Ph.D., WRF's director of grant programs. "These awards recognize that there are promising treatments being pioneered at Washington state research institutions that are so close to benefiting patients. WRF is delighted to help the researchers and the institutions take that final step in that journey from research to patient impact."

Development of new therapeutics requires considerable financial resources. These grants, along with matching funds secured by each of the awardees, aim to address this challenge and provide the necessary support to progress these innovations. The advancement of these approaches could provide much-needed alternatives for patients of chronic and rare conditions whose treatment options are currently limited.

About Washington Research Foundation:

Washington Research Foundation (WRF) supports research and scholarship in Washington state, with a focus on life sciences and enabling technologies.

WRF was founded in 1981 to assist universities and other nonprofit research institutions in Wash-ington with the commercialization and licensing of their technologies. WRF is one of the foremost technology transfer and grantmaking organizations in the nation, having earned more than $445 million in licensing revenue for the University of Washington and providing over $160 million in grants to the state's research institutions to date.

WRF Capital, the investment vehicle for Washington Research Foundation, has backed 132 local startups since 1996. Returns support the Foundation's investment and grantmaking programs.

For additional information, please visit wrfseattle.org.

Media Contact

Dale Wadman, Washington Research Foundation, (206) 336-5600, [email protected], https://www.wrfseattle.org/

SOURCE Washington Research Foundation

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