Eight promising projects win Evergreen Fund grants to promote commercialization of research

Fred Hutchinson Cancer Research Center has awarded eight grants totaling $1 million to a dozen of its scientists through the Evergreen Fund, which supports early research projects thought to be good prospects for commercial partnerships.

Since 2017, the Evergreen Fund has awarded $3 million to projects proposed by researchers seeking a timely boost to help bring their ideas from the lab bench closer to the bedside.

"Evergreen Fund grants allow researchers to complete the critical experiments that venture capital and pharma partners expect to see when evaluating a partnership opportunity,” said Hilary Hehman, the Hutch’s director of  strategic partnerships and alliances. “It’s also fantastic to have a group of seasoned investors around the table to provide feedback on all the programs, funded or not, that are evaluated.”

This year, the Evergreen Fund distributed four pilot grants of $50,000 each that are designed to give “big and bold ideas with commercial application” an infusion of funds to demonstrate the project’s potential within a six-month period. Another four projects were awarded $200,000 each to accelerate their research over a two-year period. The goal of these larger, so-called “Beyond Pilot” grants is to help researchers whose ideas are further along. They have shown promising data and a commercial path forward, but their projects need more development to attract external financial support.

Among the Beyond Pilot awardees this year are Drs. Roland Strong and Veronika Spies, who are testing ways to block a receptor, NKG2D, which they discovered is produced on the surfaces of ovarian cancer cells.

Their discovery was a major surprise, because the same receptor is normally found on immune cells, which use it to dock onto matching sites on tumors — presumably to destroy them. Strong and Spies found instead that when NKG2D is produced on the surface of cancer cells, it serves like one-half of a switch. It connects to its matching counterpart on neighboring cell surfaces, completing the switch, which in turn accelerates tumor growth. The researchers have designed a molecule that jams such connections to prevent this “self-stimulation.” They are testing this blocking protein to see if it slows or stops the growth of ovarian tumors in mice.

Other recipients of Beyond Pilot project grants

• Drs. Slobodan Beronja and Cyrus Ghajar are refining a technique to build a better mouse model for testing immune therapies for people with metastatic breast cancer. To study metastases, researchers may transplant cancer cells from one animal to another and track where these cells go. Cells can be engineered with glowing proteins for tracking, but these proteins trigger an immune reaction of their own — which is problematic for studying immunotherapies. To get around that, Beronja and Ghajar slip genes for these proteins into the developing immune systems of mice. When those mice mature, they have working immune systems that will respond to immunotherapies but will not react to tracking proteins. The technique might be useful in any preclinical research analyzing immune responses.
• Dr. Geoffrey Hill, who holds the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research, will use his award to study a promising method of protecting patients from reactivation of infection by cytomegalovirus, or CMV. Hill has shown in preclinical studies that a dose of the right antibodies — small proteins generated by immune cells — might prevent or stop a dangerous reactivation of CMV in recipients after blood stem cell transplants. High doses of pooled antibodies from many patients have been tried before as a method to suppress CMV reactivation,  but with disappointing results. Hill led mouse studies that showed antibodies could control CMV if they were matched to the strains found in each recipient prior to transplantation. The award will support forthcoming tests of this strain-specific strategy in transplant patients.
• Dr. Andrew McGuire is a leading expert on Epstein-Barr virus, or EBV, which can cause mononucleosis and is associated with certain cancers. EBV infection can be particularly dangerous for transplant patients. Although most people carry the virus without symptoms, in people with suppressed immune systems — such as transplant patients — a latent EBV infection may reactivate and lead to post-transplant lymphoproliferative disease, or PTLD. In PTLD, the virus causes unchecked proliferation of infected B cells, key components of the immune system. As many as 70% of people with this cancer-like condition will die from it. McGuire’s laboratory has isolated the first human antibody found to block EBV infection. In his project, he will develop a mouse model for PTLD to evaluate whether this promising antibody can not only block EBV, but also prevent or suppress PTLD.

Recipients of the four Evergreen Fund Pilot Awards 

• Drs. Sujatha Srinivasan and David Fredricks study organisms associated with bacterial vaginosis, or BV, a condition that increases the risk of preterm birth, pelvic inflammatory disease, HIV and other sexually transmitted diseases. It is the most common cause of vaginal discharges and is highly prevalent among women of reproductive age. Their project aims to develop a rapid and easy-to-use diagnostic test for BV. Current tests rely on access to certified labs and are costly. Srinivasan and Fredricks are studying whether the breakdown products of bacteria found in vaginal fluids might serve as biomarkers that can accurately signal the presence of BV-causing microbes with a simple, low-cost test.
• Drs. Matyas Ecsedi and Megan McAfee are developing a potentially curative immunotherapy for myeloproliferative neoplasms. These are particularly difficult-to-treat blood cancers that mostly affect older patients. The team has been genetically engineering disease-recognizing molecules on immune cells — T-cell receptors, or TCRs — to recognize a small protein from a mutation of the JAK2 gene. This flaw is found on the malignant cells of most patients with this disease. Transplantation of blood-forming stem cells is the only potentially curative therapy available for people with these cancers, but most older patients are ineligible due to concerns about the toxicity of the procedure. The researchers plan to test TCRs that recognize the mutation and evaluate these receptors for safety and effectiveness so they later can be considered for further preclinical and clinical studies.
• Dr. Anton Sholukh and colleagues are developing a new weapon to fight infections by blocking viral entry across mucosal surfaces. They designed complexes made from small nucleotides — the same durable molecules of which DNA is made — connected to proteins. They are modeled after a natural complex of proteins that coats the surface of mucus and causesviral particles to bunch up so they cannot pass through. Each laboratory-designed complex can be customized to recognize and block a specific virus, and the researchers are particularly interested in viruses that are dangerous to patients with weakened immune systems. Following tests in cell cultures, the researchers will see if the complex can stop viral infection in mice.
• Dr. Lucas Sullivan and colleagues are working to improve a drug, L-asparaginase, that has proven to be critical to improved survival of young leukemia patients since it was introduced in 1978. The drug is an enzyme produced naturally by bacteria. In turn, that enzyme breaks down an amino acid, asparagine, that the leukemia cells need to survive. Unfortunately, even as it starves cancer cells of asparagine, the enzyme can trigger dangerous allergic reactions due to its bacterial origins. The team is genetically engineering new versions of the enzyme to have traits that are more human than bacterial, and hence may be less allergenic and safer.