Engineering human pluripotent stem cells for enhanced lymphocyte development and function

University of Minnesota Ph.D. dissertation. October 2012. Major: Microbiology, Immunology and Cancer Biology. Advisor:Dan S. Kaufman, M.D., Ph.D., 1 computer file (PDF); iv, 143 pages.

[1]  D. Largaespada,et al.  A transposon and transposase system for human application. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[2]  Z. Eshhar.  Tumor-specific T-bodies: towards clinical application , 1997, Cancer Immunology, Immunotherapy.

[3]  E. Thomas.  Bone marrow transplantation: a review. , 1999, Seminars in hematology.

[4]  D. Kaufman,et al.  Pluripotent stem cell-derived natural killer cells for cancer therapy. , 2010, Translational research : the journal of laboratory and clinical medicine.

[5]  Franco Locatelli,et al.  Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. , 2003, Blood.

[6]  H. Ljunggren,et al.  Increased Infection-Related Mortality in KIR-Ligand–Mismatched Unrelated Allogeneic Hematopoietic Stem-Cell Transplantation , 2004, Transplantation.

[7]  G. Daley,et al.  Towards the generation of patient-specific pluripotent stem cells for combined gene and cell therapy of hematologic disorders. , 2007, Hematology. American Society of Hematology. Education Program.

[8]  S. Rosenberg,et al.  Minimally Cultured Tumor-infiltrating Lymphocytes Display Optimal Characteristics for Adoptive Cell Therapy , 2008, Journal of immunotherapy.

[9]  L. Zitvogel,et al.  The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression , 2006, Immunological reviews.

[10]  C. Le,et al.  Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. , 2005, Blood.

[11]  S. Rosenberg,et al.  Adoptive cell transfer: a clinical path to effective cancer immunotherapy , 2008, Nature Reviews Cancer.

[12]  Mark M Davis,et al.  A prescription for human immunology. , 2008, Immunity.

[13]  T. Schumacher,et al.  Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy , 2010, Nature Medicine.

[14]  Pei-Rong Wang,et al.  Globin phenotype of erythroid cells derived from human induced pluripotent stem cells. , 2010, Blood.

[15]  G. Dotti,et al.  Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. , 2010, Blood.

[16]  W. Yokoyama,et al.  Licensing of natural killer cells by self‐major histocompatibility complex class I , 2006, Immunological reviews.

[17]  D. Campana,et al.  Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method , 2010, Cancer Gene Therapy.

[18]  W. Yokoyama,et al.  Memory‐like responses of natural killer cells , 2010, Immunological reviews.

[19]  David K Welsh,et al.  Bioluminescence imaging in living organisms. , 2005, Current opinion in biotechnology.

[20]  S. Keirstead,et al.  Human embryonic stem cell-derived vascular progenitor cells capable of endothelial and smooth muscle cell function. , 2010, Experimental hematology.

[21]  H. Ljunggren,et al.  DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. , 2007, Cancer research.

[22]  Russell J. Taylor,et al.  Bioluminescent Imaging Demonstrates That Transplanted Human Embryonic Stem Cell‐Derived CD34+ Cells Preferentially Develop into Endothelial Cells , 2009, Stem cells.

[23]  J. Thomson,et al.  Hematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells , 2009, Stem cells.

[24]  James A. Thomson,et al.  Hematopoietic colony-forming cells derived from human embryonic stem cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Blasberg,et al.  Concurrent visualization of trafficking, expansion, and activation of T lymphocytes and T-cell precursors in vivo. , 2010, Blood.

[26]  Christopher H. Contag,et al.  In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease , 2006, Nature Reviews Immunology.

[27]  D. Kaufman,et al.  Human embryonic stem cell-derived hematopoietic cells are capable of engrafting primary as well as secondary fetal sheep recipients. , 2004, Blood.

[28]  M. Caligiuri,et al.  Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. , 1996, Blood.

[29]  M. Sadelain,et al.  Antigen-dependent CD28 Signaling Selectively Enhances Survival and Proliferation in Genetically Modified Activated Human Primary T Lymphocytes , 1998, The Journal of experimental medicine.

[30]  T. Waldmann,et al.  Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques. , 2011, Blood.

[31]  Richard P Davis,et al.  Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation. , 2005, Blood.

[32]  M. Stojkovic,et al.  Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. , 2008, Cell stem cell.

[33]  Luigi Naldini,et al.  A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. , 2012, Blood.

[34]  E. Stanley,et al.  A protocol describing the use of a recombinant protein-based, animal product-free medium (APEL) for human embryonic stem cell differentiation as spin embryoid bodies , 2008, Nature Protocols.

[35]  J. Zack,et al.  T lineage differentiation from human embryonic stem cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  R. Johnstone,et al.  Antibodies targeted to TRAIL receptor-2 and ErbB-2 synergize in vivo and induce an antitumor immune response , 2008, Proceedings of the National Academy of Sciences.

[37]  A. Howell,et al.  Human Uterine Natural Killer Cells but Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection by Secretion of CXCL12 , 2009, Journal of Virology.

[38]  M. Sadelain,et al.  Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[39]  D. Campana,et al.  2B4 (CD244) Signaling by Recombinant Antigen-specific Chimeric Receptors Costimulates Natural Killer Cell Activation to Leukemia and Neuroblastoma Cells , 2009, Clinical Cancer Research.

[40]  A. Fauci,et al.  NK cells in HIV infection: Paradigm for protection or targets for ambush , 2005, Nature Reviews Immunology.

[41]  S. Schwartz,et al.  Embryonic stem cell trials for macular degeneration: a preliminary report , 2012, The Lancet.

[42]  M. Blasco,et al.  Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. , 2009, Cell stem cell.

[43]  Jeffrey S. Miller,et al.  Use of allogeneic NK cells for cancer immunotherapy. , 2011, Immunotherapy.

[44]  J. Dick,et al.  Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic HOXB4 expression , 2005, The Journal of experimental medicine.

[45]  J. D. Di Santo,et al.  IL-15 trans-presentation promotes human NK cell development and differentiation in vivo , 2009, The Journal of experimental medicine.

[46]  M. Caligiuri,et al.  Human natural killer cells. , 2008, Blood.

[47]  R. Stewart,et al.  Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences , 2009, Science.

[48]  I. Pastan,et al.  Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains , 2009, Proceedings of the National Academy of Sciences.

[49]  L. Lanier,et al.  Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. , 1992, Journal of immunology.

[50]  F. Alt,et al.  Excision of Reprogramming Transgenes Improves the Differentiation Potential of iPS Cells Generated with a Single Excisable Vector , 2009, Stem cells.

[51]  M. Bhatia.  Hematopoietic development from human embryonic stem cells. , 2007, Hematology. American Society of Hematology. Education Program.

[52]  Oswald Steward,et al.  Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord Injury , 2005, The Journal of Neuroscience.

[53]  Jonathan L. Linehan,et al.  Efficient and Stable Transgene Expression in Human Embryonic Stem Cells Using Transposon‐Mediated Gene Transfer , 2007, Stem cells.

[54]  S. Rosenberg,et al.  T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years , 1995, Science.

[55]  Lewis L. Lanier,et al.  NK cell development, homeostasis and function: parallels with CD8+ T cells , 2011, Nature Reviews Immunology.

[56]  A. Elmaagacli,et al.  Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias. , 2005, Blood.

[57]  D. Raulet,et al.  Regulation of NK cell responsiveness to achieve self‐tolerance and maximal responses to diseased target cells , 2008, Immunological reviews.

[58]  Jing Sun,et al.  Expression of a Functional CCR2 Receptor Enhances Tumor Localization and Tumor Eradication by Retargeted Human T cells Expressing a Mesothelin-Specific Chimeric Antibody Receptor , 2011, Clinical Cancer Research.

[59]  J. Richard,et al.  HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. , 2010, Blood.

[60]  C. von Kalle,et al.  Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. , 2001, The Journal of clinical investigation.

[61]  G. Daley,et al.  Hematopoietic Development from Human Induced Pluripotent Stem Cells , 2009, Annals of the New York Academy of Sciences.

[62]  A. Consiglio,et al.  Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells , 2009, Nature.

[63]  Qi Zhou,et al.  iPS cells produce viable mice through tetraploid complementation , 2009, Nature.

[64]  Peter Lassota,et al.  Non-Invasive Detection of a Small Number of Bioluminescent Cancer Cells In Vivo , 2010, PloS one.

[65]  H. Ljunggren,et al.  Prospects for the use of NK cells in immunotherapy of human cancer , 2007, Nature Reviews Immunology.

[66]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[67]  D. Kaufman,et al.  Human Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms , 2010, Journal of Virology.

[68]  Z. Eshhar,et al.  Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Katia Perruccio,et al.  Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants , 2002, Science.

[70]  W. Linehan,et al.  Experience with the Use of High‐Dose Interleukin‐2 in the Treatment of 652 Cancer Patients , 1989, Annals of surgery.

[71]  Charles C. Kim,et al.  NK Cells and Immune “Memory” , 2011, The Journal of Immunology.

[72]  S. Rosenberg,et al.  Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[73]  Ludwig Kappos,et al.  A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. , 2010, The New England journal of medicine.

[74]  H. Ljunggren,et al.  CD56 negative NK cells: origin, function, and role in chronic viral disease. , 2010, Trends in immunology.

[75]  O. Yang,et al.  Generation of T Lineage Cells from Human Embryonic Stem Cells in a Feeder Free System , 2009, Stem cells.

[76]  L. Lybarger,et al.  Licensing of natural killer cells by host major histocompatibility complex class I molecules , 2005, Nature.

[77]  S. Yamanaka,et al.  Orderly hematopoietic development of induced pluripotent stem cells via Flk‐1+ hemoangiogenic progenitors , 2009, Journal of cellular physiology.

[78]  A. Fischer,et al.  Gene therapy of inherited diseases , 2008, The Lancet.

[79]  Konstantin A Lukyanov,et al.  Near-infrared fluorescent proteins , 2010, Nature Methods.

[80]  Michael Z. Lin,et al.  Autofluorescent proteins with excitation in the optical window for intravital imaging in mammals. , 2009, Chemistry & biology.

[81]  K. Skak,et al.  Interleukin‐21 activates human natural killer cells and modulates their surface receptor expression , 2008, Immunology.

[82]  Jonathan L. Linehan,et al.  Hematopoietic Engraftment of Human Embryonic Stem Cell‐Derived Cells Is Regulated by Recipient Innate Immunity , 2006, Stem cells.

[83]  L. Hurton,et al.  Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells , 2012, PloS one.

[84]  T. Ben-Hur,et al.  Stable genetic modification of human embryonic stem cells by lentiviral vectors. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[85]  M. Vodyanik,et al.  Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell-derived lin-CD34+CD43+CD45+ progenitors. , 2009, The Journal of clinical investigation.

[86]  D. Armstrong.  Relapsed ovarian cancer: challenges and management strategies for a chronic disease. , 2002, The oncologist.

[87]  J. Thomson,et al.  High‐Level Sustained Transgene Expression in Human Embryonic Stem Cells Using Lentiviral Vectors , 2003, Stem cells.

[88]  J. Wagner,et al.  4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies. , 2010, Human gene therapy.

[89]  T. Waldmann.  The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design , 2006, Nature Reviews Immunology.

[90]  R. Jain,et al.  TGF-β Blockade Controls Ascites by Preventing Abnormalization of Lymphatic Vessels in Orthotopic Human Ovarian Carcinoma Models , 2011, Clinical Cancer Research.

[91]  M. Berg,et al.  Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells. , 2009, Cytotherapy.

[92]  D. Campana,et al.  Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. , 2009, Cancer research.

[93]  Robin Goland,et al.  Generation of pluripotent stem cells from patients with type 1 diabetes , 2009, Proceedings of the National Academy of Sciences.

[94]  P. Woll,et al.  Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells. , 2008, Blood.

[95]  J. Thomson,et al.  Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. , 2005, Blood.

[96]  D. Kaufman.  Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells. , 2009, Blood.

[97]  W. Wels,et al.  Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. , 2009, Leukemia research.

[98]  Linzhao Cheng,et al.  Functional antigen-presenting leucocytes derived from human embryonic stem cells in vitro , 2004, The Lancet.

[99]  Evelina Mazzolari,et al.  Gene Therapy in Peripheral Blood Lymphocytes and Bone Marrow for ADA− Immunodeficient Patients , 1995, Science.

[100]  Lewis L Lanier,et al.  Natural killer cell receptor signaling. , 2003, Current opinion in immunology.

[101]  G. Daley,et al.  Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. , 2010, Cell stem cell.

[102]  G. Daley,et al.  The promise and perils of stem cell therapeutics. , 2012, Cell stem cell.

[103]  C. Dang,et al.  Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. , 2009, Blood.

[104]  S. Murphy,et al.  The activated transforming growth factor‐beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer , 2012, International journal of cancer.

[105]  George Q. Daley,et al.  Disease-Specific Induced Pluripotent Stem Cells , 2008, Cell.

[106]  D. Kaufman,et al.  Human embryonic stem cell-derived CD34+ cells function as MSC progenitor cells. , 2010, Bone.

[107]  S. Ogawa,et al.  Derivation of functional mature neutrophils from human embryonic stem cells. , 2009, Blood.

[108]  S. Morrison,et al.  An in vivo model to study and manipulate the hematopoietic stem cell niche. , 2010, Blood.

[109]  C. Lutz,et al.  Mouse fetal and embryonic liver cells differentiate human umbilical cord blood progenitors into CD56-negative natural killer cell precursors in the absence of interleukin-15. , 2008, Experimental hematology.

[110]  R. Jaenisch,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2007, Nature.

[111]  S. Rosenberg,et al.  Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. , 1988, The New England journal of medicine.

[112]  E. Bouhassira,et al.  Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells. , 2008, Blood.

[113]  G. Hall,et al.  Human Tumour Immune Evasion via TGF-β Blocks NK Cell Activation but Not Survival Allowing Therapeutic Restoration of Anti-Tumour Activity , 2011, PloS one.

[114]  P. Ravassard,et al.  Quantitative Comparison of Constitutive Promoters in Human ES cells , 2010, PloS one.

[115]  E. Alici,et al.  Natural killer cell‐based immunotherapy in cancer: current insights and future prospects , 2009, Journal of internal medicine.

[116]  Liping Yang,et al.  Cytokine-induced memory-like natural killer cells , 2009, Proceedings of the National Academy of Sciences.

[117]  C. Croce,et al.  A potential role for interleukin-15 in the regulation of human natural killer cell survival. , 1997, The Journal of clinical investigation.

[118]  P. Woll,et al.  Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity. , 2009, Blood.

[119]  B. Vandekerckhove,et al.  In vitro generation of immune cells from pluripotent stem cells. , 2011, Frontiers in bioscience.

[120]  S. Rosenberg,et al.  T-cell therapy at the threshold , 2012, Nature Biotechnology.

[121]  A. Jha,et al.  Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. , 2012, Blood.

[122]  George Q. Daley,et al.  Reprogramming of human somatic cells to pluripotency with defined factors , 2008, Nature.

[123]  Michel Sadelain,et al.  Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase , 2009, Nature Medicine.

[124]  A. Trounson,et al.  Genetic modification of human embryonic stem cells for derivation of target cells. , 2008, Cell stem cell.

[125]  J. Passweg,et al.  IL-2−driven Regulation of NK Cell Receptors With Regard to the Distribution of CD16+ and CD16− Subpopulations and In Vivo Influence After Haploidentical NK Cell Infusion , 2010, Journal of immunotherapy.

[126]  Louis M. Weiner,et al.  Monoclonal antibodies: versatile platforms for cancer immunotherapy , 2010, Nature Reviews Immunology.

[127]  J. Gong,et al.  Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. , 1994, Leukemia.

[128]  A. Hayday,et al.  The habitual, diverse and surmountable obstacles to human immunology research , 2008, Nature Immunology.

[129]  E. Stanley,et al.  Differentiation of Human Embryonic Stem Cells in Serum‐Free Medium Reveals Distinct Roles for Bone Morphogenetic Protein 4, Vascular Endothelial Growth Factor, Stem Cell Factor, and Fibroblast Growth Factor 2 in Hematopoiesis , 2007, Stem cells.

[130]  L. Downs,et al.  A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. , 2011, Cytotherapy.

[131]  A. Bagg,et al.  Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. , 2011, The New England journal of medicine.

[132]  P. Woll,et al.  Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity1 , 2005, The Journal of Immunology.

[133]  Chap T Le,et al.  Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. , 2010, Blood.

[134]  Jonathan L. Linehan,et al.  Cytokine requirements differ for stroma and embryoid body-mediated hematopoiesis from human embryonic stem cells. , 2004, Experimental hematology.

[135]  C. Hughes,et al.  Of Mice and Not Men: Differences between Mouse and Human Immunology , 2004, The Journal of Immunology.

[136]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[137]  R. Jaenisch,et al.  Generation of iPSCs from cultured human malignant cells. , 2010, Blood.

[138]  H. Pircher,et al.  CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. , 2010, Blood.

[139]  Michel Sadelain,et al.  Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRζ /CD28 receptor , 2002, Nature Biotechnology.

[140]  Michel Sadelain,et al.  Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. , 2011, Blood.

[141]  R. Stewart,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[142]  M. Brenner,et al.  Fifteen years of gene therapy based on chimeric antigen receptors: "are we nearly there yet?". , 2009, Human gene therapy.