title: Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.
abstract: There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.
authors.affiliation: Division of Hematology-Oncology, The David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America. skitchen@ucla.edu
authors.forename: Scott G
authors.initials: SG
authors.lastname: Kitchen
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Zoran
authors.initials: Z
authors.lastname: Galić
authors.forename: Joanne
authors.initials: J
authors.lastname: Kim
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Alan
authors.initials: A
authors.lastname: Young
authors.forename: Alexis
authors.initials: A
authors.lastname: Lieberman
authors.forename: Aviva
authors.initials: A
authors.lastname: Joseph
authors.forename: Harris
authors.initials: H
authors.lastname: Goldstein
authors.forename: Hwee
authors.initials: H
authors.lastname: Ng
authors.forename: Otto
authors.initials: O
authors.lastname: Yang
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology*; D005818:Genetic Engineering; D006678:HIV / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000302:isolation & purification; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell