Current translational and clinical practices in hematopoietic cell and gene therapy

Drolet, 2011, Translational research: understanding the continuum from bench to bedside, Translation Res J Lab Clin Med, 157, 1, 10.1016/j.trsl.2010.10.002 Zerhouni, 2006, Clinical research at a crossroads: the NIH roadmap, J Invest Med, 54, 171, 10.2310/6650.2006.X0016 Westfall, 2007, Practice-based research: ‘Blue Highways’ on the NIH roadmap, J Am Med Assoc, 297, 403, 10.1001/jama.297.4.403 Silvestri, 1992, The CD34 hemopoietic progenitor cell associated antigen: biology and clinical applications, Haematologica, 77, 265 Bensinger, 1995, Factors that influence collection and engraftment of autologous peripheral-blood stem cells, J Clin Oncol, 13, 2547, 10.1200/JCO.1995.13.10.2547 Naldini, 2011, Ex vivo gene transfer and correction for cell-based therapies, Nat Rev Genet., 12, 301, 10.1038/nrg2985 Riviere, 2012, Hematopoietic stem cell engineering at a crossroads, Blood, 119, 1107, 10.1182/blood-2011-09-349993 Butturini, 1987, Graft-versus-leukemia following bone marrow transplantation, Bone Marrow Transplant, 2, 233 Zaia, 2002, Prevention and management of CMV-related problems after hematopoietic stem cell transplantation, Bone Marrow Transplant, 29, 633, 10.1038/sj.bmt.1703407 Aguilar, 1999, Lymphoproliferative disorders involving Epstein–Barr virus after hemopoietic stem cell transplantation, Curr Opin Oncol, 11, 96, 10.1097/00001622-199903000-00004 Howard, 1999, Adenovirus infections in hematopoietic stem cell transplant recipients, Clin Infect Dis, 29, 1494, 10.1086/313514 Greenberg, 1991, Adoptive immunotherapy of human cytomegalovirus infection: potential role in protection from disease progression, Transplant Proc, 23, 97 Riddell, 1992, Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones, Science, 257, 238, 10.1126/science.1352912 Walter, 1995, Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor, N Engl J Med, 333, 1038, 10.1056/NEJM199510193331603 Heslop, 1996, Long-term restoration of immunity against Epstein– Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes, Nat Med, 2, 551, 10.1038/nm0596-551 Gottschalk, 2003, Generating CTLs against the subdominant Epstein–Barr virus LMP1 antigen for the adoptive immunotherapy of EBV-associated malignancies, Blood, 101, 1905, 10.1182/blood-2002-05-1514 Leen, 2004, Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications, Blood, 103, 1011, 10.1182/blood-2003-07-2449 O'Reilly, 2007, Adoptive transfer of antigen-specific T-cells of donor type for immunotherapy of viral infections following allogeneic hematopoietic cell transplants, Immunol Res, 38, 237, 10.1007/s12026-007-0059-2 Becker, 2001, Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture assay, Nat Med, 7, 1159, 10.1038/nm1001-1159 Chatziandreou, 2007, Capture and generation of adenovirus specific T cells for adoptive immunotherapy, Br J Haematol, 136, 117, 10.1111/j.1365-2141.2006.06386.x Kerns, 2010, B cell-specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia, Blood, 115, 2146, 10.1182/blood-2009-09-241869 Leen, 2006, Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals, Nat Med, 12, 1160, 10.1038/nm1475 Leen, 2009, Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein–Barr virus infections after haploidentical and matched unrelated stem cell transplantation, Blood, 114, 4283, 10.1182/blood-2009-07-232454 Hanley, 2011, Expansion of T cells targeting multiple antigens of cytomegalovirus, Epstein–Barr virus and adenovirus to provide broad antiviral specificity after stem cell transplantation, Cytotherapy, 13, 976, 10.3109/14653249.2011.575356 Heslop, 2010, Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients, Blood, 115, 925, 10.1182/blood-2009-08-239186 Peggs, 2003, Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines, Lancet, 362, 1375, 10.1016/S0140-6736(03)14634-X Zandvliet, 2010, Co-ordinated isolation of CD8(+) and CD4(+) T cells recognizing a broad repertoire of cytomegalovirus pp65 and IE1 epitopes for highly specific adoptive immunotherapy, Cytotherapy, 12, 933, 10.3109/14653240903505822 Cruz, 2010, Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience, Cytotherapy, 12, 743, 10.3109/14653241003709686 Sili, 2012, Production of good manufacturing practice-grade cytotoxic T lymphocytes specific for Epstein–Barr virus, cytomegalovirus and adenovirus to prevent or treat viral infections post-allogeneic hematopoietic stem cell transplant, Cytotherapy, 14, 7, 10.3109/14653249.2011.636963 Rosenberg, 1990, Gene transfer into humans: immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction, N Engl J Med, 323, 570, 10.1056/NEJM199008303230904 Dudley, 2003, Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients, J Immunother, 26, 332, 10.1097/00002371-200307000-00005 Dudley, 2008, Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens, J Clin Oncol, 26, 5233, 10.1200/JCO.2008.16.5449 Rosenberg, 2009, Adoptive cell therapy for the treatment of patients with metastatic melanoma, Curr Opin Immunol, 21, 233, 10.1016/j.coi.2009.03.002 Rosenberg, 2011, Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy, Clin Cancer Res, 17, 4550, 10.1158/1078-0432.CCR-11-0116 Gajewski, 2006, Immune resistance orchestrated by the tumor microenvironment, Immunol Rev, 213, 131, 10.1111/j.1600-065X.2006.00442.x Gattinoni, 2005, Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells, J Exp Med, 202, 907, 10.1084/jem.20050732 Kim, 2010, Features of responding T cells in cancer and chronic infection, Curr Opin Immunol, 22, 223, 10.1016/j.coi.2010.02.005 Baitsch, 2011, Exhaustion of tumor-specific CD8 T cells in metastases from melanoma patients, J Clin Invest, 121, 2350, 10.1172/JCI46102 Ohta, 1992, Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer, Cancer, 70, 741, 10.1002/1097-0142(19920815)70:4<741::AID-CNCR2820700405>3.0.CO;2-5 Baxevanis, 1994, Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer, Cancer, 74, 1275, 10.1002/1097-0142(19940815)74:4<1275::AID-CNCR2820740416>3.0.CO;2-Q Kass, 2003, Restoration of tumor-specific HLA class I restricted cytotoxicity in tumor infiltrating lymphocytes of advanced breast cancer patients by in vitro stimulation with tumor antigen-pulsed autologous dendritic cells, Breast Cancer Res Treat, 80, 275, 10.1023/A:1024938215782 Santin, 2004, Restoration of tumor specific human leukocyte antigen class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer, Int J Gynecol Cancer, 14, 64, 10.1111/j.1048-891x.2004.014175.x Turcotte, 2011, Immunotherapy for metastatic solid cancers, Adv Surg, 45, 341, 10.1016/j.yasu.2011.04.003 Semino, 1999, Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience, Anticancer Res, 19, 5645 Porter, 2006, A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation, Blood, 107, 1325, 10.1182/blood-2005-08-3373 Rapoport, 2011, Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma, Blood, 117, 788, 10.1182/blood-2010-08-299396 Clay, 1999, Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity, J Immunol, 163, 507 Fujio, 2000, Functional reconstitution of class II MHC-restricted T cell immunity mediated by retroviral transfer of the alpha beta TCR complex, J Immunol, 165, 528, 10.4049/jimmunol.165.1.528 Cooper, 2000, Transfer of specificity for human immunodeficiency virus type 1 into primary human T lymphocytes by introduction of T-cell receptor genes, J Virol, 74, 8207, 10.1128/JVI.74.17.8207-8212.2000 Morgan, 2010, Adoptive cell therapy: genetic modification to redirect effector cell specificity, Cancer J, 16, 336, 10.1097/PPO.0b013e3181eb3879 Eshhar, 1993, 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, Proc Natl Acad Sci USA, 90, 720, 10.1073/pnas.90.2.720 McKeever, 1996, Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein: antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization, J Exp Med, 184, 1755, 10.1084/jem.184.5.1755 Brentjens, 2010, Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial, Mol Ther, 18, 666, 10.1038/mt.2010.31 Peinert, 2009, Chimeric T cells for adoptive immunotherapy of cancer: using what have we learned to plan for the future, Immunotherapy, 1, 905, 10.2217/imt.09.69 Levine, 2008, T lymphocyte engineering ex vivo for cancer and infectious disease, Expert Opin Biol Ther, 8, 475, 10.1517/14712598.8.4.475 Park, 2007, Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma, Mol Ther, 15, 825, 10.1038/sj.mt.6300104 Kohn, 2011, CARs on track in the clinic, Mol Ther, 19, 432, 10.1038/mt.2011.1 Berger, 2006, Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation, Blood, 107, 2294, 10.1182/blood-2005-08-3503 Jensen, 2010, Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans, Biol Blood Marrow Transplant, 16, 1245, 10.1016/j.bbmt.2010.03.014 Hernandez-Chacon, 2011, Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function, J Immunother, 34, 236, 10.1097/CJI.0b013e318209e7ec Hombach, 2011, Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28-OX40 signalling, Int J Cancer, 129, 2935, 10.1002/ijc.25960 Kowolik, 2006, CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells, Cancer Res, 66, 10995, 10.1158/0008-5472.CAN-06-0160 Milone, 2009, Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo, Mol Ther, 17, 1453, 10.1038/mt.2009.83 Song, 2011, In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB), Cancer Res, 71, 4617, 10.1158/0008-5472.CAN-11-0422 Cooper, 2004, Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies, Blood Cells Mol Dis, 33, 83, 10.1016/j.bcmd.2004.03.003 Kochenderfer, 2009, Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor, J Immunother, 32, 689, 10.1097/CJI.0b013e3181ac6138 Kochenderfer, 2010, Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells, Blood, 116, 3875, 10.1182/blood-2010-01-265041 Singh, 2011, Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies, Cancer Res, 71, 3516, 10.1158/0008-5472.CAN-10-3843 Terakura, 2012, Generation of CD19-chimeric antigen receptor modified CD8 + T cells derived from virus-specific central memory T cells, Blood, 119, 72, 10.1182/blood-2011-07-366419 Hollyman, 2009, Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy, J Immunother, 32, 169, 10.1097/CJI.0b013e318194a6e8 Brentjens, 2011, Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias, Blood, 118, 4817, 10.1182/blood-2011-04-348540 Porter, 2011, Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia, N Engl J Med, 365, 725, 10.1056/NEJMoa1103849 Gattinoni, 2005, Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells, J Clin Invest, 115, 1616, 10.1172/JCI24480 Hinrichs, 2009, Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity, Proc Natl Acad Sci USA, 106, 17469, 10.1073/pnas.0907448106 Hinrichs, 2011, Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy, Blood, 117, 808, 10.1182/blood-2010-05-286286 Lan, 2010, Cationic liposome coupled endostatin gene for treatment of peritoneal colon cancer, Clin Exp Metastasis, 27, 307, 10.1007/s10585-010-9328-x Berger, 2008, Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates, J Clin Invest, 118, 294, 10.1172/JCI32103 Turtle, 2009, A distinct subset of self-renewing human memory CD8+ T cells survives cytotoxic chemotherapy, Immunity, 31, 834, 10.1016/j.immuni.2009.09.015 Gennery, 2010, Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better?, J Allergy Clin Immunol, 126, 602, 10.1016/j.jaci.2010.06.015 Szabolcs, 2010, Bone marrow transplantation for primary immunodeficiency diseases, Pediatr Clin North Am, 57, 207, 10.1016/j.pcl.2009.12.004 Prasad, 2010, Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions, Br J Haematol, 148, 356, 10.1111/j.1365-2141.2009.07974.x Hutter, 2011, Allogeneic haematopoietic stem cell transplantation in patients with human immunodeficiency virus: the experiences of more than 25 years, Clin Exp Immunol, 163, 284, 10.1111/j.1365-2249.2010.04312.x Bordignon, 1995, Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients, Science, 270, 470, 10.1126/science.270.5235.470 Aiuti, 2002, Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning, Science, 296, 2410, 10.1126/science.1070104 Kohn, 1998, T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34+ cells in ADA-deficient SCID neonates, Nat Med, 4, 775, 10.1038/nm0798-775 Aiuti, 2009, Gene therapy for immunodeficiency due to adenosine deaminase deficiency, N Engl J Med, 360, 447, 10.1056/NEJMoa0805817 Ljungman, 2010, Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009, Bone Marrow Transplant, 45, 219, 10.1038/bmt.2009.141 Hacein-Bey-Abina, 2008, Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1, J Clin Invest, 118, 3132, 10.1172/JCI35700 Howe, 2008, Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients, J Clin Invest, 118, 3143, 10.1172/JCI35798 Gaspar, 2011, Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency, Sci Transl Med, 3, 97ra79, 10.1126/scitranslmed.3002715 Thrasher, 2005, Failure of SCID-X1 gene therapy in older patients, Blood, 105, 4255, 10.1182/blood-2004-12-4837 Boztug, 2010, Stem-cell gene therapy for the Wiskott–Aldrich syndrome, N Engl J Med, 363, 1918, 10.1056/NEJMoa1003548 Stein, 2010, Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease, Nat Med, 16, 198, 10.1038/nm.2088 Ott, 2006, Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1, Nat Med, 12, 401, 10.1038/nm1393 Scholler, 2012, Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells, Sci Transl Med, 4, 132ra53, 10.1126/scitranslmed.3003761 Cartier, 2009, Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy, Science, 326, 818, 10.1126/science.1171242 Biffi, 2011, Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection, Blood, 117, 5332, 10.1182/blood-2010-09-306761 Cavazzana-Calvo, 2010, Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia, Nature, 467, 318, 10.1038/nature09328 Nathwani, 2011, Adenovirus-associated virus vector-mediated gene transfer in hemophilia B, N Engl J Med, 365, 2357, 10.1056/NEJMoa1108046 Roy, 2010, Ocular gene therapy: an evaluation of recombinant adeno-associated virus-mediated gene therapy interventions for the treatment of ocular disease, Hum Gene Ther, 21, 915, 10.1089/hum.2010.041 DiGiusto, 2010, RNA-based gene therapy for HIV with lentiviral vector-modified CD34(+) cells in patients undergoing transplantation for AIDS-related lymphoma, Sci Transl Med., 10.1126/scitranslmed.3000931 Krishnan, 2005, Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas, Blood, 105, 874, 10.1182/blood-2004-04-1532 Holt, 2010, Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo, Nat Biotechnol, 28, 839, 10.1038/nbt.1663 Podsakoff, 2005, Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells, Mol Ther, 12, 77, 10.1016/j.ymthe.2005.02.024 Zinno, 2011, Processing of hematopoietic stem cells from peripheral blood before cryopreservation: use of a closed automated system, Transfusion, 51, 2656, 10.1111/j.1537-2995.2011.03180.x Janssen, 2010, Large-scale Ficoll gradient separations using a commercially available, effectively closed, system, Cytotherapy, 12, 418, 10.3109/14653240903479663 Aktas, 2008, Separation of adult bone marrow mononuclear cells using the automated closed separation system Sepax, Cytotherapy, 10, 203, 10.1080/14653240701851324 Powell, 2009, Efficient clinical-scale enrichment of lymphocytes for use in adoptive immunotherapy using a modified counterflow centrifugal elutriation program, Cytotherapy, 11, 923, 10.3109/14653240903188921 Perseghin, 2008, Isolation of monocytes from leukapheretic products for large-scale GMP-grade generation of cytomegalovirus-specific T-cell lines by means of an automated elutriation device, Transfusion, 48, 1644, 10.1111/j.1537-2995.2008.01756.x Kim, 2007, Monocyte enrichment from leukapheresis products by using the Elutra cell separator, Transfusion, 47, 2290, 10.1111/j.1537-2995.2007.01470.x Gonzalez-Vicent, 2010, Graft manipulation and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation from mismatched unrelated and mismatched/haploidentical related donors in pediatric leukemia patients, J Pediatr Hematol Oncol, 32, 85, 10.1097/MPH.0b013e3181cf813c Devine, 2011, Biol Blood Marrow Transplant, 17, 1343, 10.1016/j.bbmt.2011.02.002 Prieto, 2010, Enrichment of CD8+ cells from melanoma tumor-infiltrating lymphocyte cultures reveals tumor reactivity for use in adoptive cell therapy, J Immunother, 33, 547, 10.1097/CJI.0b013e3181d367bd Feuchtinger, 2010, Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation, Blood, 116, 4360, 10.1182/blood-2010-01-262089 Di Nicola, 2009, Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study, Blood, 113, 18, 10.1182/blood-2008-06-165654 Hardy, 2012, Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation, Blood., 119, 2956, 10.1182/blood-2011-09-378398 Brunstein, 2011, Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics, Blood, 117, 1061, 10.1182/blood-2010-07-293795 Rapoport, 2009, Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of costimulated autologous T cells, Clin Cancer Res, 15, 4499, 10.1158/1078-0432.CCR-09-0418 Bernstein, 2004, Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4(+) T cells to HIV-infected persons, Clin Immunol, 111, 262, 10.1016/j.clim.2004.03.004 Orchard, 2002, Clinical-scale selection of anti-CD3/CD28-activated T cells after transduction with a retroviral vector expressing herpes simplex virus thymidine kinase and truncated nerve growth factor receptor, Hum Gene Ther, 13, 979, 10.1089/10430340252939087 Notta, 2011, Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment, Science, 333, 218, 10.1126/science.1201219 Klebanoff, 2005, Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells, Proc Natl Acad Sci USA, 102, 9571, 10.1073/pnas.0503726102 Gattinoni, 2011, A human memory T cell subset with stem cell-like properties, Nat Med, 17, 1290, 10.1038/nm.2446 Spanholtz, 2011, Clinical-grade generation of active NK cells from cord blood hematopoietic progenitor cells for immunotherapy using a closed-system culture process, PLoS One, 6, e20740, 10.1371/journal.pone.0020740 Sensebe, 2008, Clinical grade production of mesenchymal stem cells, Biomed Mater Eng, 18, S3 Tran, 2007, Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity, J Immunother, 30, 644, 10.1097/CJI.0b013e318052e1f4 Vera, 2010, Accelerated production of antigen-specific T cells for preclinical and clinical applications using gas-permeable rapid expansion cultureware (G-Rex), J Immunother, 33, 305, 10.1097/CJI.0b013e3181c0c3cb Sadeghi, 2011, Large-scale bioreactor expansion of tumor-infiltrating lymphocytes, J Immunol Methods, 364, 94, 10.1016/j.jim.2010.11.007 Hami, 2004, GMP production and testing of Xcellerated T cells for the treatment of patients with CLL, Cytotherapy, 6, 554, 10.1080/14653240410005348 Delaney, 2010, Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution, Nat Med, 16, 232, 10.1038/nm.2080 Choi, 2012, Notch-induced hIL-6 production facilitates the maintenance of self-renewal of hCD34+ cord blood cells through the activation of Jak-PI3K-STAT3 pathway, Am J Pathol, 180, 351, 10.1016/j.ajpath.2011.09.030 Auvray, 2012, HOXC4 homeoprotein efficiently expands human hematopoietic stem cells and triggers similar molecular alterations as HOXB4, Haematologica, 97, 168, 10.3324/haematol.2011.051235 Watts, 2011, Hematopoietic stem cell expansion facilitates multilineage engraftment in a nonhuman primate cord blood transplantation model, Exp Hematol., 40, 187, 10.1016/j.exphem.2011.11.009 Boitano, 2010, Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells, Science, 329, 1345, 10.1126/science.1191536 Horn, 2003, Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice compared with nonhuman primates, Blood, 102, 4329, 10.1182/blood-2003-01-0082 Mezquita, 2008, NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon, Gene Ther, 15, 1460, 10.1038/gt.2008.108 Kohn, 2007, Lentiviral vectors ready for prime-time, Nat Biotechnol, 25, 65, 10.1038/nbt0107-65 Papanikolaou, 2010, Major challenges for gene therapy of thalassemia and sickle cell disease, Curr Gene Ther, 10, 404, 10.2174/156652310793180724 Dropulic, 2011, Lentiviral vectors: their molecular design, safety, and use in laboratory and preclinical research, Hum Gene Ther, 22, 649, 10.1089/hum.2011.058 Klages, 2000, A stable system for the high-titer production of multiply attenuated lentiviral vectors, Mol Ther, 2, 170, 10.1006/mthe.2000.0103 Farson, 2001, A new-generation stable inducible packaging cell line for lentiviral vectors, Hum Gene Ther, 12, 981, 10.1089/104303401750195935 Xu, 2001, Generation of a stable cell line producing high-titer self-inactivating lentiviral vectors, Mol Ther, 3, 97, 10.1006/mthe.2000.0238 Ni, 2005, Generation of a packaging cell line for prolonged large-scale production of high-titer HIV-1-based lentiviral vector, J Gene Med, 7, 818, 10.1002/jgm.726 Witting SR, Li LH, Jasti A, Allen C, Cornetta K, Brady J, . Efficient large volume lentiviral vector production using flow electroporation. Hum Gene Ther. Volume 23(2): 243–9. Pacchia, 2001, An inducible packaging cell system for safe, efficient lentiviral vector production in the absence of HIV-1 accessory proteins, Virology, 282, 77, 10.1006/viro.2000.0787 Broussau, 2008, Inducible packaging cells for large-scale production of lentiviral vectors in serum-free suspension culture, Mol Ther, 16, 500, 10.1038/sj.mt.6300383 Stewart, 2009, Development of inducible EIAV-based lentiviral vector packaging and producer cell lines, Gene Ther, 16, 805, 10.1038/gt.2009.20 Merten, 2011, Large-scale manufacture and characterization of a lentiviral vector produced for clinical ex vivo gene therapy application, Hum Gene Ther, 22, 343, 10.1089/hum.2010.060 Lombardo, 2007, Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery, Nat Biotechnol, 25, 1298, 10.1038/nbt1353 Doyon, 2011, Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures, Nat Methods, 8, 74, 10.1038/nmeth.1539 Miller, 2007, An improved zinc-finger nuclease architecture for highly specific genome editing, Nat Biotechnol, 25, 778, 10.1038/nbt1319 Urnov, 2005, Highly efficient endogenous human gene correction using designed zinc-finger nucleases, Nature, 435, 646, 10.1038/nature03556 Carroll, 2006, Design, construction and in vitro testing of zinc finger nucleases, Nat Protoc, 1, 1329, 10.1038/nprot.2006.231 Porteus, 2006, Mammalian gene targeting with designed zinc finger nucleases, Mol Ther, 13, 438, 10.1016/j.ymthe.2005.08.003 Kim, 1996, Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain, Proc Natl Acad Sci USA, 93, 1156, 10.1073/pnas.93.3.1156 Cannon, 2011, Chemokine receptor 5 knockout strategies, Curr Opin HIV AIDS, 6, 74, 10.1097/COH.0b013e32834122d7 Wilen, 2011, Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases, PLoS Pathog, 7, e1002020, 10.1371/journal.ppat.1002020 Sebastiano, 2011, In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases, Stem Cells, 29, 1717, 10.1002/stem.718 Li, 2011, In vivo genome editing restores haemostasis in a mouse model of haemophilia, Nature, 475, 217, 10.1038/nature10177 Yusa, 2011, Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells, Nature, 478, 391, 10.1038/nature10424 Ramalingam, 2011, Creating designed zinc-finger nucleases with minimal cytotoxicity, J Mol Biol, 405, 630, 10.1016/j.jmb.2010.10.043 Cornu, 2010, Quantification of zinc finger nuclease-associated toxicity, Methods Mol Biol, 649, 237, 10.1007/978-1-60761-753-2_14 Pruett-Miller, 2009, Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels, PLoS Genet, 5, e1000376, 10.1371/journal.pgen.1000376 Pattanayak, 2011, Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection, Nat Methods, 8, 765, 10.1038/nmeth.1670 Li L, Piatek MJ, Atef A, Piatek A, Wibowo A, Fang X, . Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification. Plant Mol Biol. 78:407–16. Mussolino, 2011, A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity, Nucleic Acids Res, 39, 9283, 10.1093/nar/gkr597 Arnould, 2006, Engineering of large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets, J Mol Biol, 355, 443, 10.1016/j.jmb.2005.10.065 Stoddard, 2011, Homing endonucleases: from microbial genetic invaders to reagents for targeted DNA modification, Structure, 19, 7, 10.1016/j.str.2010.12.003 Burnett, 2011, Current progress of siRNA/shRNA therapeutics in clinical trials, Biotechnol J, 6, 1130, 10.1002/biot.201100054 Ehsani, 2010, Rational design of micro-RNA-like bifunctional siRNAs targeting HIV and the HIV coreceptor CCR5, Mol Ther, 18, 796, 10.1038/mt.2009.321 Chattopadhyay, 2009, Inhibition of hepatitis B virus replication with linear DNA sequences expressing antiviral micro-RNA shuttles, Biochem Biophys Res Commun, 389, 484, 10.1016/j.bbrc.2009.09.004 Shrivastava, 2008, RNA interference: an emerging generation of biologicals, Biotechnol J, 3, 339, 10.1002/biot.200700215 Izquierdo, 2005, Short interfering RNAs as a tool for cancer gene therapy, Cancer Gene Ther, 12, 217, 10.1038/sj.cgt.7700791 Brown, 2009, Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications, Nat Rev Genet, 10, 578, 10.1038/nrg2628 Zhong, 2010, Knockdown of hTERT by SiRNA suppresses growth of Capan-2 human pancreatic cancer cell via the inhibition of expressions of Bcl-2 and COX-2, J Dig Dis, 11, 176, 10.1111/j.1751-2980.2010.00433.x Li, 2003, Inhibition of HIV-1 infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs, Mol Ther, 8, 196, 10.1016/S1525-0016(03)00165-5 Anderson, 2007, Complete knockdown of CCR5 by lentiviral vector-expressed siRNAs and protection of transgenic macrophages against HIV-1 infection, Gene Ther, 14, 1287, 10.1038/sj.gt.3302958 Kunze, 2008, Multitarget siRNA inhibition of antiapoptotic genes (XIAP, BCL2, BCL-X(L)) in bladder cancer cells, Anticancer Res, 28, 2259 Brown, 2007, Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state, Nat Biotechnol, 25, 1457, 10.1038/nbt1372 Ciceri, 2009, Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study, Lancet Oncol, 10, 489, 10.1016/S1470-2045(09)70074-9 Di Stasi, 2011, Inducible apoptosis as a safety switch for adoptive cell therapy, N Engl J Med, 365, 1673, 10.1056/NEJMoa1106152 Kaneko, 2009, IL-7 and IL-15 allow the generation of suicide gene-modified alloreactive self-renewing central memory human T lymphocytes, Blood, 113, 1006, 10.1182/blood-2008-05-156059 Li, 2010, Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method, Cancer Gene Ther, 17, 147, 10.1038/cgt.2009.61 Liu, 2008, Delivery of whole tumor lysate into dendritic cells for cancer vaccination, Methods Mol Biol, 423, 139, 10.1007/978-1-59745-194-9_9 Hackett, 2010, A transposon and transposase system for human application, Mol Ther, 18, 674, 10.1038/mt.2010.2 McLachlan, 2011, Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung, Gene Ther, 18, 996, 10.1038/gt.2011.55 Fenske, 2008, Liposomal nanomedicines: an emerging field, Toxicol Pathol, 36, 21, 10.1177/0192623307310960 Hosseinkhani, 2006, Self assembly of DNA nanoparticles with polycations for the delivery of genetic materials into cells, J Nanosci Nanotechnol, 6, 2320, 10.1166/jnn.2006.507 Orlando, 2010, Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology, Nucleic Acids Res, 38, e152, 10.1093/nar/gkq512 Benabdallah, 2010, Targeted gene addition to human mesenchymal stromal cells as a cell-based plasma-soluble protein delivery platform, Cytotherapy, 12, 394, 10.3109/14653240903583803 Papapetrou, 2011, Genomic safe harbors permit high beta-globin transgene expression in thalassemia induced pluripotent stem cells, Nat Biotechnol, 29, 73, 10.1038/nbt.1717 Gersbach, 2011, Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase, Nucleic Acids Res, 39, 7868, 10.1093/nar/gkr421 Russom, 2012, Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing, Cytotherapy, 14, 114, 10.3109/14653249.2011.619007 Trounson, 2012, Stem cell biology: towards the reality of cell therapeutics, Nature Cell Biology, 14, 331, 10.1038/ncb2469 Trounson, 2012, The alpha stem cell clinic: a model for evaluating and delivering stem cell-based therapies, Stem Cells Trans Med, 1, 9, 10.5966/sctm.2011-0027