Research Topics
Genomes and Genes | Barbara SavoldoSummaryAffiliation: Baylor College of Medicine Country: USA Publications
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Publications
Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs)Barbara Savoldo
Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, 6621 Fannin St, MC 3 3320, Houston, TX 77030, USA
Blood 108:2942-9. 2006..These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity...- Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin diseaseBarbara Savoldo
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX 77030, USA
Blood 110:2620-30. 2007..EBV-CTLs expressing both a native and a chimeric antigen receptor may therefore have added value for treatment of HD... - Generation of Epstein-Barr virus-specific cytotoxic T lymphocytes resistant to the immunosuppressive drug tacrolimus (FK506)Biagio De Angelis
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX 77030, USA
Blood 114:4784-91. 2009.... - T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor modelAntonio Di Stasi
Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital and Texas Children s Hospital, Houston, 77030, USA
Blood 113:6392-402. 2009..This approach may be of value in patients affected by HL... - Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytesConcetta Quintarelli
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
Blood 110:2793-802. 2007..We found that the incorporation of an inducible caspase-9 suicide gene allowed efficient elimination of transgenic CTLs after exposure to a chemical inducer of dimerization, thereby increasing the safety and feasibility of the approach... - Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantationKenneth P Micklethwaite
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital, Houston, TX, USA
Blood 115:2695-703. 2010..This approach may prove beneficial for patients with high-risk B-ALL who have recently received an HSC or CB transplant and are at risk of infection and relapse... 
Quantification of a low cellular immune response to aid in identification of pediatric liver transplant recipients at high-risk for EBV infectionTimothy C Lee
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
Clin Transplant 20:689-94. 2006..Because measurement of EBV DNA load as a single parameter has a poor positive predictive value for development of PTLD, the association of these assays may be of help in the identification of patients at risk for PTLD...- Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipientsTimothy C Lee
Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
Clin Transplant 20:389-93. 2006..Herein we describe the use of cytokine polymorphisms and real-time quantitative polymerase chain reaction (qPCR) Epstein-Barr virus (EBV) viral load to identify patients at risk for PTLD development... - Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastomaChrystal U Louis
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital, Houston, TX, USA
Blood 118:6050-6. 2011..This study is registered at www.clinialtrials.gov as #NCT00085930... - Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7Juan F Vera
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Houston, Texas 77030, USA
Mol Ther 17:880-8. 2009..This approach may allow selective expansion of CTLs without the unwanted effects associated with IL-2... - Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infectionBarbara Savoldo
Center for Cell and Gene Therapy, Houston, TX 77030, USA
Blood 100:4059-66. 2002.... - Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipientsTimothy C Lee
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA
Am J Transplant 5:2222-8. 2005..05). These findings illustrate that frequent EBV viral load monitoring and preemptive immunosuppression modulation have an integral role in preventing PTLD in the pediatric liver transplant population... - Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopesPatrick J Hanley
Department of Immunology, Baylor College of Medicine, Texas Children s Hospital and The Methodist Hospital, Center for Cell and Gene Therapy, Houston, TX 77030, USA
Blood 114:1958-67. 2009..This study is registered at www.clinicaltrials.gov as NCT00078533... - CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patientsBarbara Savoldo
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
J Clin Invest 121:1822-6. 2011.... - Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemiaConcetta Quintarelli
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX 77030, USA
Blood 112:1876-85. 2008..PRAME CTLs were generated almost exclusively from the naive T-cell compartment, and clonal analysis showed these cells could have high alphabetaTCR-peptide avidity. PRAME CTLs or vaccines may thus be of value for patients with CML... - T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cellsJuan Vera
Center for Cell and Gene Therapy, Baylor College of Medicine, Fannin St, MC 3-3320, Houston, TX 77030, USA
Blood 108:3890-7. 2006.... - Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastomaMartin A Pule
Center for Cell and Gene Therapy, Baylor College of Medicine and The Methodist Hospital and Texas Children s Hospital, Houston, Texas 77030, USA
Nat Med 14:1264-70. 2008..Infusion of these genetically modified cells seemed safe and was associated with tumor regression or necrosis in half of the subjects tested. Hence, virus-specific CTLs can be modified to function as tumor-directed effector cells... - T cells expressing constitutively active Akt resist multiple tumor-associated inhibitory mechanismsJiali Sun
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA
Mol Ther 18:2006-17. 2010..In conclusion, caAkt-transduced T cells showed resistance to several evasion strategies employed by tumors and may therefore enhance the antitumor activity of adoptively transferred T lymphocytes... - Combining mTor Inhibitors With Rapamycin-resistant T Cells: A Two-pronged Approach to Tumor EliminationLeslie E Huye
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
Mol Ther 19:2239-48. 2011..CD19-28ζ T cells or rapa alone. In conclusion, the combination of rapa and rapa-resistant, CAR.CD19-28ζ-expressing T cells may provide a novel therapy for the treatment of B cell malignancies and other cancers... - Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphomaUlrike Gerdemann
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children s Hospital, Houston, Texas 77030, USA
Mol Ther 19:2258-68. 2011..Infusion of such multispecific monocultures may extend the benefits of CTL therapy to treatment even of EBV negative HL and NHL... - Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomasZhensheng Liu
Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
Recent Results Cancer Res 159:123-33. 2002.... - Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ(null) miceSimon N Robinson
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Exp Hematol 40:445-56. 2012..We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting... - Selective depletion of a minor subpopulation of B-chronic lymphocytic leukemia cells is followed by a delayed but progressive loss of bulk tumor cells and disease regressionAaron E Foster
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX, 77030 USA
Mol Cancer 8:106. 2009..This outcome supports the presence of a rare population of precursor/progenitor cells in human malignancies, and suggests benefit from their removal... - Gene therapy to improve migration of T cells to the tumor siteAntonio Di Stasi
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX, USA
Methods Mol Biol 651:103-18. 2010.... - High-avidity cytotoxic T lymphocytes specific for a new PRAME-derived peptide can target leukemic and leukemic-precursor cellsConcetta Quintarelli
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
Blood 117:3353-62. 2011..These PRAME-directed CTLs did not affect normal hematopoietic progenitors, indicating that this approach may be of value for immunotherapy of PRAME(+) hematologic malignancies... - T cells redirected against CD70 for the immunotherapy of CD70-positive malignanciesDonald R Shaffer
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital, Houston, TX 77030, USA
Blood 117:4304-14. 2011..Adoptively transferred CD70-specific T cells induced sustained regression of established murine xenografts. Therefore, CD70-specific T cells may be a promising immunotherapeutic approach for CD70-positive malignancies... - Fifteen years of gene therapy based on chimeric antigen receptors: "are we nearly there yet?"Gianpietro Dotti
Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital, Houston, TX 77030, USA
Hum Gene Ther 20:1229-39. 2009..In this review we summarize the concept of CAR-based immunotherapy, describe the steps accomplished, and outline the future progress we need to make if this approach is truly to improve cancer immunotherapy... - Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cellsEric Yvon
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
Clin Cancer Res 15:5852-60. 2009..Moreover, these transgenic receptors can be directed to tumor-associated antigens that are not protein-derived, such as the ganglioside GD2, which is expressed in a high proportion of melanoma cells... - Cellular therapy of Epstein-Barr-virus-associated post-transplant lymphoproliferative diseaseHelen E Heslop
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hosptial and Texas Children s Hospital, Houston, TX 77030, USA
Best Pract Res Clin Haematol 17:401-13. 2004..The use of genetically modified T cells or newer suicide genes may result in improved safety and efficacy. Current challenges are to define indications for immunotherapy or antibody therapy in patients with incipient or overt PTLD... - Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative diseaseCatherine M Bollard
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA
Acta Haematol 110:139-48. 2003..The infusion of EBV-CTL has been demonstrated to be safe and effective in allogeneic HSCT recipients and their use post-SOT is being evaluated... - Regression of experimental medulloblastoma following transfer of HER2-specific T cellsNabil Ahmed
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital, The Methodist Hospital, Houston, Texas 77030, USA
Cancer Res 67:5957-64. 2007..In contrast, delivery of nontransduced T cells did not change the tumor growth pattern. Adoptive transfer of HER2-specific T cells may represent a promising immunotherapeutic approach for medulloblastoma... - Targeted delivery of adenoviral vectors by cytotoxic T cellsPatricia Yotnda
Center for Cell and Gene Therapy, 6621 Fannin St, MC3 3320, Houston, TX 77030, USA
Blood 104:2272-80. 2004.... - Gene therapy to improve function of T cells for adoptive immunotherapyConcetta Quintarelli
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children s Hospital, Houston, TX, USA
Methods Mol Biol 651:119-30. 2010..We found that the incorporation of an inducible caspase-9 suicide gene allowed efficient elimination of transgenic CTLs after exposure to a chemical inducer of dimerization, thereby increasing the safety and feasibility of the approach... - Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative diseaseBarbara Savoldo
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital and The Methodist Hospital, Houston, Texas, USA
Am J Transplant 5:566-72. 2005..Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve... - Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosisGianpietro Dotti
Center for Cell and Gene Therapy, Baylor College of Medicine, 6621 Fannin St, MC 3 3320, Houston, TX 77030, USA
Blood 105:4677-84. 2005..EBV-CTLs with knocked down Fas should have a selective functional and survival advantage over unmodified EBV-CTLs in the presence of tumors expressing FasL and may be of value for adoptive cellular therapy... - Changes in chemokine receptor expression of regulatory T cells after ex vivo cultureRikhia Chakraborty
Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, Methodist Hospital and Texas Children s Hospital, Houston, TX 77030, USA
J Immunother 35:329-36. 2012..Our analyses suggest that ex vivo cultured Tregs may display impaired or suboptimal migration to the inflamed tissues releasing RANTES and MIP-1α chemokines... - Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individualsBarbara Savoldo
Center for Cell and Gene Therapy and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
J Immunol 168:909-18. 2002..In addition, our method for selecting EBV-specific CTL from naive individuals by precursor cell enrichment may be applicable to the immunotherapy of cancer patients with a low frequency of tumor- or virus-specific CTL... - Inducible apoptosis as a safety switch for adoptive cell therapyAntonio Di Stasi
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children s Hospital, Houston, TX 77030, USA
N Engl J Med 365:1673-83. 2011..When exposed to a synthetic dimerizing drug, the inducible caspase 9 (iCasp9) becomes activated and leads to the rapid death of cells expressing this construct... - Immunotherapy for post-transplant lymphoproliferative diseaseKarin C M Straathof
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
Br J Haematol 118:728-40. 2002 - Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applicationsAnn M Leen
Center for Cell and Gene Therapy, Department of Pediatrics, 6621 Fannin S, MC 3-3320, Houston, TX 77030, USA
Blood 103:1011-9. 2004..This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTLs), which should be protective against the range of different Ad subtypes that affect transplant recipients... - Activation of wnt signaling arrests effector differentiation in human peripheral and cord blood-derived T lymphocytesSujatha Muralidharan
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030
J Immunol 187:5221-32. 2011..The arrest in T cell differentiation induced by Wnt signaling might have relevant clinical applications such as to preserve the naive T cell compartment in Ag-specific T cells generated ex vivo for adoptive T cell immunotherapy... - Noninvasive bioluminescent imaging demonstrates long-term multilineage engraftment of ex vivo-expanded CD34-selected umbilical cord blood cellsDavid Steiner
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Stem Cells 27:1932-40. 2009..The results suggest that multipotent stem cells can be expanded ex vivo and can contribute meaningfully to long-term hematopoietic engraftment... - Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experienceConrad Russell Cruz
Dan L Duncan Cancer Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital, Texas Children s Hospital, Houston, Texas 77030, USA
Cytotherapy 12:743-9. 2010..Recent catastrophic reactions to 'first-in-man' biologic agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious... - Transgenic expression of CD40 ligand produces an in vivo antitumor immune response against both CD40(+) and CD40(-) plasmacytoma cellsGianpietro Dotti
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
Blood 100:200-7. 2002..Hence, transgenic CD40L expression may produce an antimyeloma immune response against either CD40(+) or CD40(-) tumors and may be of therapeutic value for both types of myeloma in humans... - PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activationWenjing Sun
Texas Children s Cancer Center, Department of Pediatrics, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States
Cell Signal 21:95-102. 2009..These data suggest that PPM1A and PPM1B play an important role in the termination of TNFalpha-mediated NF-kappaB activation through dephosphorylating and inactivating IKKbeta... - What influence has B-cell depletion on viral infections?Anjum S Kaka
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
Leuk Lymphoma 48:1257-8. 2007
Research Grants
- Improving Function and Persistence of Chimeric T CellsBarbara Savoldo; Fiscal Year: 2006..The data produced by this project will be crucial to develop appropriate clinical trails with redirected T cells. ..
- Chimeric T Cell for Therpay of Hodgkin DiseaseBarbara Savoldo; Fiscal Year: 2010..We now want to extend the application of this promising treatment by targeting other proteins that are on all HD cells, and by making the immune cells more potent. ..