The Gates Grubstake Fund invokes the memory of Gold Rush prospectors who received seed money, “grubstakes,” for food and supplies so they could search for treasure. The funding supports the work of modern-day prospectors – translational researchers affiliated with Gates Institute – whose work developing cell- and gene-based therapies could make a difference in human lives. In 2022, four awardees received $350,000 each to support their work.
In addition, second-tranche awards are made to eligible previous Grubstake recipients who have demonstrated success in developing technology toward a clinical trial using original Grubstake funding, along with evidence that additional funding would allow them to reach an additional inflection point toward commercialization.
In total, over $1.5 million was awarded by the Gates Grubstake Fund to CU Anschutz researchers.
2022 Gates Grubstake Awardees
Ganna Bilousova, PhD: Somatic Cell Rejuvenation for Skin Transplantation and Wound Healing
With a steady increase in the aging population, the care of acute and chronic wounds in the elderly has become a priority topic for clinicians. Many options to treat wounds are currently available. However, none of them restores the functionality of aged skin cells, hence low success rate in the elderly. Ganna Bilousova, PhD, associate professor of dermatology, and Igor Kogut, PhD, assistant professor of dermatology, are developing a permanent corrective therapy for acute and chronic wounds in the elderly by rejuvenating the patient’s own skin cells using a patent-pending RNA cocktail of factors. The Grubstake Award will allow their teams to finalize their therapeutic product and compare its efficacy with the competition to accelerate development toward pre-investigational new drug (IND) filing with the Food & Drug Administration.
Mi-Hyun Nam, PhD: Restoration of Vision in Glaucoma Through Cell Therapy
Principal investigator Mi-Hyun Nam, PhD, research instructor in ophthalmology, and her co-PI, Natalia Vergara, PhD, assistant professor of ophthalmology, are developing a human stem cell-based therapy for treating glaucoma, the second-leading cause of blindness worldwide. Current medical therapies are limited to lowering intraocular pressure, which may prevent further vision loss, but no treatment to date can restore vision once it has been lost. The Grubstake funding will enable them to perform preclinical studies to determine the feasibility and efficacy of their therapy.
Eric Kohler, MD, PhD: Adjunctive LAT-Activating Chimeric Antigen Receptor T cells (ALA-CART) Strengths
CAR-T cells have revolutionized the treatment of leukemia and lymphoma, inducing responses against cancers that no longer respond to traditional therapies. However, current CAR-T cell strategies are unable to induce long-term remissions in the majority of patients, owing to limitations in their persistence, potency and sensitivity. By studying CAR-T cell signaling, the lab of Eric Kohler, MD, PhD, assistant professor in the Department of Pediatrics, identified that inefficient activation of the molecule LAT was responsible for many of the limitations in current CAR-T cell therapies. Using this finding, they rationally designed a new Adjunctive LAT-Activating CAR-T cell (ALA-CART) that restores LAT signaling and demonstrates enhanced potency and persistence in preclinical models. Furthermore, ALA-CART cells demonstrated increased sensitivity to tumor cells with low levels of the targeted antigen, allowing for eradication of leukemia that would otherwise not be “seen” by current CAR-T cell therapies. These advancements hold the potential to close many of the vulnerabilities of CAR-T cell therapies and improve their long-term effectiveness for patients. Grubstake funding will be used to generate safety data and establish manufacturing workflows at the Gates Biomanufacturing Facility to transition this work to clinical trials.
Daniel Sherbenou, MD, PhD: Response Prediction for T Cell Engaging Bispecific Antibodies in Multiple Myeloma
Daniel Sherbenou, MD, PhD, associate professor in hematology, Department of Medicine, received a Gates Grubstake Award to commercialize the new myeloma drug sensitivity testing (My-DST) assay for profiling responses to T cell engaging bispecific antibodies for patients with multiple myeloma, an incurable blood cancer afflicting more than 150,000 Americans. Bispecific antibodies are a promising new class of therapy that redirect a patient’s own T cells to kill the cancerous myeloma cells. To improve the clinical application of these drugs, My-DST has potential as a new laboratory test for measuring responses of an individual patient’s tumor cells from biopsy specimens. In this project, Sherbenou’s team will pursue regulatory approvals and scale up efforts to establish My-DST as a personalize medicine approach for the various bispecific antibodies in clinical use or in clinical trials.
Second-Tranche Grubstake Recipients
Michael Verneris, MD: Multiomic Approach to Establish Mechanisms of Efficacy of Stem Cell-Derived Innate Lymphoid Cells in Gastrointestinal Tract Repair
Michael Verneris, MD, professor in the Department of Pediatrics, received a second-tranche award of $100,000. Innate lymphoid cells are tissue resident lymphocytes that can be restorative to injured mucosal tissues. In Crohn’s disease (CD), a subpopulation of ILCs (ILC3’s) are depleted and the loss of these cells is thought to be part of the pathogenesis of CD. Replacement of ILC3’s in CD may be therapeutic. Verneris’ laboratory has developed methods to generate ILC3’s from hematopoietic stem cells and has found that adoptive transfer of these cells can improve the intestinal dysfunction in TNFdARE mice, which is a model of CD. With this funding they will perform CITE-SEQ and Xenium in situ analysis on ILC3 treated (and untreated) mice to better understand the impact of ILC3’s adoptive transfer at single cell resolution. Additionally, they will continue to perform scale-up experiments with the goal of transferring this technology to the Gates Biomanufacturing Facility.
Eduardo Davila, PhD: Manufacturing of Genetically Engineered Tumor Infiltrating Lymphocyte (TIL) Therapy
Eduardo Davila, PhD, professor in the Division of Medical Oncology, was awarded $50,000 in second-tranche funds. This funding will accelerate development toward pre-IND filing with the FDA by completing studies related to (1) specificity and potency assays to test TIL function; investigate changes in the T cell repertoire; and confirm that TILs do not become leukemic.