T-cell genetic modification for re-directed tumor recognition.
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Female↗
Biomedical subjects
David DiGiusto
Publications and source records attributed to David DiGiusto.
Hematopoietic potential of neural stem cells: plasticity versus heterogeneity.
Organ-specific stem cells have been identified in a variety of mammalian tissues. These cells hold great promise for cellular therapy if they can reliably produce functional progeny of specific lineages. A central dogma in development has been that organ-specific stem cells are restricted to making the differentiated cell types of the tissue from which they are isolated. However, a substantial body of evidence exists that stem-cell populations from neural and hematopoietic tissues can generate the other cell types, suggesting that adult organ-specific stem cells may have a broader differentiation potential than originally thought. It remains unclear whether this apparent stem cell plasticity is attributable to transdifferentiation of tissue specific stem cells, the co-existence of multiple stem cells with different potentials, or resident totipotent stem cells in these tissues. Recent evidence, in fact, indicates that there may be a fourth explanation for the "apparent" plasticity of stem cells: cell fusion. Here, the authors critically examine the existing data to assess the extent of phenotypic conversion of bone marrow-to-brain and brain-to-blood and discuss some of the contentious issues surrounding these studies. We conclude that there is strong evidence for a multipotent neurohematopoietic stem-cell population in human and mouse brain, although further characterization of these cells will be required if the goal of engineering tissues for therapeutic applications is to be realized.
Animals↗
Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies.
The graft-versus-leukemia (GVL)-effect achieved by donor-derived T cells arising from transplanted allogeneic hematopoietic stem cells or given as donor-leukocyte infusions (DLI) after allogeneic transplant, demonstrates that donor-derived T cells can eradicate B-lineage malignancies. However, graft-versus-host-disease (GVHD) occurring after allogeneic hematopoietic stem-cell transplant (HSCT) or polyclonal DLI can limit the efficacy of these interventions. This toxicity can be avoided by using autologous T cells and/or tumor-specific cytotoxic T lymphocytes (CTLs). To generate antigen-specific T cells that can be derived from the allogeneic donor or the patient, we have genetically manipulated T cells to express a CD19-specific chimeric immunoreceptor. This renders T cells specific for CD19, a cell surface molecule found on B-lineage leukemia and lymphoma. This review will demonstrate the redirected specificity of CD19-specific T cells and implementation of clinical trials using these cellular agents.
Antigens, CD19↗