Disease Focus: Solid Tumors
Development of novel small molecules against cancer stem cells in solid cancers
Research Objective To study and optimize lead compounds with multi-kinase activity against existing glioma stem cells and radiation-induced phenotype conversion of non-stem glioma cells into induced glioma stem cells. Impact Glioblastoma is a universally deadly disease. While radiotherapy prolongs survival in glioblastoma it has hit a critical barrier. The proposed study aims to improve the […]
CAR T cells targeting abnormal N-glycans for the treatment of refractory/metastatic solid cancers
Research Objective Develop genetically modified chimeric antigen receptor T cells to kill incurable solid cancers by targeting a previously un-targetable tumor associated carbohydrate antigen. Impact Refractory/metastatic solid cancers are almost always incurable and have limited therapeutic options. Directing the immune system to kill cancer cells provides an unprecedented new approach. Major Proposed Activities Engineer and […]
Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells
Research Objective HSC-engineered allogeneic mesothelin-targeting CAR-iNKT (AlloMCAR-iNKT) cells Impact treatment of ovarian cancer Major Proposed Activities Milestone 1. Production of the AlloMCAR-iNKT cells Milestone 2. Characterization of the AlloMCAR-iNKT cells Milestone 3. Delivery of the new therapeutic candidate Ovarian cancer (OC) is the leading cause of death among women with gynecological malignancies. In the USA, […]
Targeting pancreatic cancer stem cells with DDR1 antibodies.
Research Objective A therapeutic antibody to DDR1 for targeting pancreatic cancer stem cells to overcome resistance to chemotherapy and potentiate the treatment of advanced cancer. Impact PDAC is lethal cancer that poorly responds chemotherapy to which it becomes resistant. DDR1 antagonistic Abs should improve chemotherapy responsiveness and may cause tumor regression as a monotherapy. Major […]
Development of a novel stem-cell based carrier for intravenous delivery of oncolytic viruses
Research Objective Develop a stem cell-based platform that safely and efficiently delivers viruses that specifically kill tumor cells and restore immune activity in patients with advanced cancer. Impact Overcome the inherent limitations that prevent efficient intravenous delivery of tumor killing viruses to metastatic tumors. Major Proposed Activities Compare the relative efficacy of native or cargocyte-delivered […]
Preclinical development of an exhaustion-resistant CAR-T stem cell for cancer immunotherapy
Research Objective The expected outcome is an exhaustion-resistant CAR-T cell, which persists long-term in a functional progenitor T cell state in the tumor microenvironment and can be used for cancer immunotherapy. Impact CAR-T cells are effective in B cell cancer, but less than 50% of patients experience long-term disease control. Exhaustion-resistant CARs may provide long-term […]
Human iPSC-derived chimeric antigen receptor expressing macrophages for improved 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 […]
Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury
Research Objective These preclinical studies will discover the efficacy of stem cell-derived, nanoscale, extracellular vesicles (candidate) to treat adverse effects of cancer therapy on brain function and cognition. Impact Stem cell-derived extracellular vesicles will address the confounders of stem cells (tumors, immunorejection, immunosuppression) & mitigate debilitating side-effects of cancer therapy on the brain. Major Proposed […]
Targeting Critical Regulators of Cancer Stem Cells
Research Objective We will develop a small molecule inhibitor that blocks the growth of human pancreatic cancer and AML cancer stem cells in vitro and in vivo. Impact This work will lead to a new treatment for cancer stem cell driven diseases such as AML and pancreatic cancer. In addition, it will improve the prognosis […]
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 […]