Project Objective: Development Candidate
Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia
Research Objective The objectives of this study are to advance a stem cell gene therapy for the immunodeficiency XLA, defining the final therapeutic candidate and showing therapeutic activity in a relevant mouse model. Impact XLA can be treated with chronic immunoglobulin replacement, but may be sub-optimal due to infections and inflammatory complications. Stem cell gene […]
Modulation of the Wnt pathway to restore inner ear function
Research Objective We aim to identify drug regimens that stimulate endogenous progenitors in the inner to regenerate to restore hearing or balance functions. Impact Treatment for irreversible hearing loss and balance disorders is limited, a drug regimen to reverse is highly impactful. Major Proposed Activities Production of R-spondin proteins Drug testing in neonatal cochlear cultures […]
Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment
Research Objective These studies will produce a new CAR-targeted iPSC-derived macrophage-based cell therapy product for treatment of refractory malignancies such as ovarian cancer. Impact These studies eliminate a bottleneck in macrophage production and enable these cells to be engineered and manufactured in a standardized, off-the-shelf manner, rather than on a patient-specific basis. Major Proposed Activities […]
Therapeutic immune tolerant human islet-like organoids (HILOs) for Type 1 Diabetes
Research Objective Development of immune tolerant human islet-like organoids for transplantation into diabetic patients. Impact Our proposal will progress the development of an unlimited, reproducible source of immune tolerant engineered islets for transplantation into Type I diabetics. Major Proposed Activities Demonstrate efficacy of immune tolerant HILOs in humanized diabetic mice Demonstrate safety of immune tolerant […]
Preclinical Development of An HSC-Engineered Off-The-Shelf iNKT Cell Therapy for Cancer
Research Objective The expected outcome is a therapeutic candidate, allogeneic HSC-engineered HLA-I/II-negative human iNKT cells, that can potentially be used as an off-the-shelf cellular therapy for treating cancer. Impact The proposed off-the-shelf HSC-engineered iNKT therapy has the potential to become a general cancer immunotherapy for treating multiple cancers and a large population of cancer patients. […]
Develop iPSC-derived microglia to treat progranulin-deficient Frontotemporal Dementia
Research Objective Develop stem cell-based therapy to treat dementia Impact There are no treatments for dementia. If successfully achieved, this study will lead to a cure of a familial
 form of dementia in the elderly population. Major Proposed Activities Develop a robust human stem cell-derived microglial platform for cell-based therapy Determine short-term safety and efficacy […]
Genetically Modified Hematopoietic Stem Cells for the Treatment of Danon Disease
Research Objective We propose to discover a novel, genetically modified hematopoietic stem cell based treatment for Danon disease, a rare lysosomal storage disease that affects the heart. Impact As the only existing treatment for Danon disease is cardiac transplant, this therapy would significantly meet an unmet need. It also may help many other similar diseases. […]
Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome
Research Objective We propose a platform to generate transplantable thymus organoids derived from human pluripotent stem cells designed to treat severe immunodeficiencies in children affected by 22q11 DS Impact Our product could impact 22q11DS and many other pathologies characterized by absence, degeneration or injury of the thymus and resulting in severe immunodeficiencies. Major Proposed Activities […]
Chimeric Antigen Receptor-Engineered Stem/Memory T Cells for the Treatment of Recurrent Ovarian Cancer
Research Objective We are developing a tumor-associated glycan-targeting CAR T cell with inducible cytokine production that drives T cell stem/memory phenotype and persistence for effective treatment of ovarian cancer. Impact 25% of ovarian cancer patients recur within 6 months. Targeting cancer stem cells with a persistent progenitor CAR T cell product offers a potent strategy […]
Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer
Research Objective We will 1) identify non-invasive bladder cancer patients with (pre)cancerous urothelium by single-cell RNA-seq and 2) replace this dangerous lesion with normal hESC-derived bladder progenitors. Impact Replacement of corrupted (pre)cancerous urothelium with pluripotent cell-derived normal bladder progenitors will provide a definitive treatment for bladder cancer, expected to eliminate recurrence. Major Proposed Activities To […]