title: Modeling Human Leukemia Immunotherapy in Humanized Mice.
abstract: The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse) model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL), which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI), a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Xia
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; The First Hospital and Institute of Immunology, Jilin University, Changchun, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; The First Hospital and Institute of Immunology, Jilin University, Changchun, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; The First Hospital and Institute of Immunology, Jilin University, Changchun, China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Jin
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; The First Hospital and Institute of Immunology, Jilin University, Changchun, China.
authors.forename: Shulian
authors.initials: S
authors.lastname: Tan
authors.affiliation: The First Hospital and Institute of Immunology, Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Humanized Mouse Unit, Institute of Molecular and Cell Biology, ASTAR, Singapore; Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology, Singapore.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.affiliation: Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA; The First Hospital and Institute of Immunology, Jilin University, Changchun, China. Electronic address: yy2324@columbia.edu.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes; D018183:Transplantation Chimera
chemical_list: D018952:Antigens, CD34
keywords: Humanized mice; Leukemia; Lymphopenia; Mixed-lineage leukemia fusion gene; Recipient leukocyte infusion