Richard A Morgan

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. doi request reprint Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase
    Timothy L Frankel
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:5988-98. 2010
  2. pmc Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma
    Richard A Morgan
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 23:1043-53. 2012
  3. pmc Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy
    Richard A Morgan
    Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
    J Immunother 36:133-51. 2013
  4. pmc High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens
    Richard A Morgan
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 171:3287-95. 2003
  5. doi request reprint Adoptive cell therapy: genetic modification to redirect effector cell specificity
    Richard A Morgan
    Surgery Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, USA
    Cancer J 16:336-41. 2010
  6. pmc Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2
    Richard A Morgan
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Ther 18:843-51. 2010
  7. pmc A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas
    William R Burns
    Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 70:3027-33. 2010
  8. pmc Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen
    Laura A Johnson
    Surgery Branch, Hatfield Clinical Research Center, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Blood 114:535-46. 2009
  9. pmc Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors
    Michal Lotem
    Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
    J Immunother 29:616-27. 2006
  10. pmc Cancer regression in patients after transfer of genetically engineered lymphocytes
    Richard A Morgan
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Science 314:126-9. 2006

Detail Information

Publications79

  1. doi request reprint Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase
    Timothy L Frankel
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:5988-98. 2010
    ..These results suggest that this highly active tyrosinase-specific TCR could be of value in adoptive cell transfer for melanoma...
  2. pmc Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma
    Richard A Morgan
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 23:1043-53. 2012
    ..Based on these observations, a γ-retroviral vector expressing this EGFRvIII CAR was produced for clinical application...
  3. pmc Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy
    Richard A Morgan
    Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
    J Immunother 36:133-51. 2013
    ....
  4. pmc High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens
    Richard A Morgan
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 171:3287-95. 2003
    ..These results suggest that lymphocytes genetically engineered to express anti-gp100 TCR may be of value in the adoptive immunotherapy of patients with melanoma...
  5. doi request reprint Adoptive cell therapy: genetic modification to redirect effector cell specificity
    Richard A Morgan
    Surgery Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, USA
    Cancer J 16:336-41. 2010
    ..Initial clinical trial results have demonstrated that both T-cell receptor- and chimeric antigen receptor-engineered T cells can be administered to cancer patients and mediate tumor regression...
  6. pmc Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2
    Richard A Morgan
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Ther 18:843-51. 2010
    ..We speculate that the large number of administered cells localized to the lung immediately following infusion and were triggered to release cytokine by the recognition of low levels of ERBB2 on lung epithelial cells...
  7. pmc A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas
    William R Burns
    Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 70:3027-33. 2010
    ..This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies...
  8. pmc Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen
    Laura A Johnson
    Surgery Branch, Hatfield Clinical Research Center, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Blood 114:535-46. 2009
    ..This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175...
  9. pmc Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors
    Michal Lotem
    Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
    J Immunother 29:616-27. 2006
    ..These data suggest that DCs transduced with viral vectors may be more efficient than DCs transfected with cDNAs or RNAs for the induction of tumor reactive CD8+ and CD4+ T cells in vitro and in human vaccination trials...
  10. pmc Cancer regression in patients after transfer of genetically engineered lymphocytes
    Richard A Morgan
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Science 314:126-9. 2006
    ..This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer...
  11. doi request reprint A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity
    Yangbing Zhao
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 183:5563-74. 2009
    ..More importantly, PBLs expressing this new version of the 4D5 CAR could not only efficiently lyse the autologous fresh tumor digests, but they could strongly suppress tumor growth in a xenogenic mouse model...
  12. pmc Evaluation of γ-retroviral vectors that mediate the inducible expression of IL-12 for clinical application
    Ling Zhang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    J Immunother 35:430-9. 2012
    ..These results support the clinical application of adoptive transfer of young TIL engineered with the NFAT.hIL12 vector as a new approach for cancer immunotherapy...
  13. pmc T-cell receptor gene therapy of established tumors in a murine melanoma model
    John D Abad
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunother 31:1-6. 2008
    ..This model may be a powerful tool for evaluating future TCR gene transfer-based strategies...
  14. pmc Recognition of NY-ESO-1+ tumor cells by engineered lymphocytes is enhanced by improved vector design and epigenetic modulation of tumor antigen expression
    Jennifer A Wargo
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Immunol Immunother 58:383-94. 2009
    ..These results have relevance for TCR-based gene therapies targeting common epithelial malignancies...
  15. pmc Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy
    Christian S Hinrichs
    National Cancer Institute, Bethesda, MD, USA
    Blood 117:808-14. 2011
    ..Thus, these data suggest that naive cells resist terminal differentiation, or "exhaustion," maintain high replicative potential, and therefore may be the superior subset for use in adoptive immunotherapy...
  16. pmc Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions
    Marybeth S Hughes
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 16:457-72. 2005
    ..TCR-transduced T-cells are thus attractive candidates for evaluation in cell transfer therapies of patients with cancer...
  17. doi request reprint A simplified method for the clinical-scale generation of central memory-like CD8+ T cells after transduction with lentiviral vectors encoding antitumor antigen T-cell receptors
    Shicheng Yang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunother 33:648-58. 2010
    ..The methodology described here could be readily applied for engineering CD8+ T cells with antitumor specificity for human adoptive immunotherapy...
  18. pmc Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes
    Laura A Johnson
    Surgery Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 177:6548-59. 2006
    ..We propose that inducing expression of this highly avid TCR in patient PBMC has the potential to induce tumor regression, as an "off-the-shelf" reagent for allogeneic melanoma patient gene therapy...
  19. pmc Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice
    Dhanalakshmi Chinnasamy
    Surgery Branch, National Cancer Institute, Clinical Research Center, Bethesda, Maryland 20892, USA
    J Clin Invest 120:3953-68. 2010
    ..T cells transduced with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers...
  20. pmc Extrathymic generation of tumor-specific T cells from genetically engineered human hematopoietic stem cells via Notch signaling
    Yangbing Zhao
    Surgery Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1201, USA
    Cancer Res 67:2425-9. 2007
    ..The genetic manipulation of HSCs has broad implications for ACT of cancer...
  21. pmc Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR
    Cyrille J Cohen
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 175:5799-808. 2005
    ..These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies...
  22. pmc Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor
    James N Kochenderfer
    Surgery Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunother 32:689-702. 2009
    ....
  23. pmc Genetic engineering of murine CD8+ and CD4+ T cells for preclinical adoptive immunotherapy studies
    Sid P Kerkar
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunother 34:343-52. 2011
    ..These results indicate that preclinical murine models of adoptive immunotherapies are more practical using γ-retroviral rather than lentiviral vectors...
  24. pmc Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions
    Paul F Robbins
    Surgery Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunol 180:6116-31. 2008
    ....
  25. pmc In vitro generated anti-tumor T lymphocytes exhibit distinct subsets mimicking in vivo antigen-experienced cells
    Shicheng Yang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Cancer Immunol Immunother 60:739-49. 2011
    ....
  26. pmc Relationship of p53 overexpression on cancers and recognition by anti-p53 T cell receptor-transduced T cells
    Marc R Theoret
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1201, USA
    Hum Gene Ther 19:1219-32. 2008
    ..These studies raise doubts concerning the suitability of targeting p53 in the immunotherapy of cancer patients...
  27. pmc Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2
    Bianca Heemskerk
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 19:496-510. 2008
    ..In this study, insertion of the IL-2 gene into antitumor TILs increased their ability to survive after IL-2 withdrawal in vitro but did not increase their in vivo persistence or clinical effectiveness...
  28. pmc Clinical-scale lentiviral vector transduction of PBL for TCR gene therapy and potential for expression in less-differentiated cells
    Shicheng Yang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Immunother 31:830-9. 2008
    ..Compared with gamma-retroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population...
  29. pmc Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts
    Sid P Kerkar
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
    Cancer Res 70:6725-34. 2010
    ..Our findings reveal an approach to genetically modify T cells to reduce the cell number needed, eliminate the need for vaccines or systemic IL-2, and improve immunotherapy efficacy based on adoptive transfer of gene-engineered T cells...
  30. pmc Lentiviral vector design for optimal T cell receptor gene expression in the transduction of peripheral blood lymphocytes and tumor-infiltrating lymphocytes
    Stephanie Jones
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 20:630-40. 2009
    ..This paper emphasizes the need to optimize both promoter function and protein synthesis in constructs that require stoichiometric production of multiple protein subunits...
  31. pmc Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1
    Paul F Robbins
    National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892 1201, USA
    J Clin Oncol 29:917-24. 2011
    ....
  32. pmc A simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes
    Shicheng Yang
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther Methods 23:73-83. 2012
    ..We describe a simple, efficient, and low-cost method for the production of clinical-grade LVV for ex vivo gene therapy protocols...
  33. pmc Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR genes recognize and kill diverse human tumor cell lines
    Yangbing Zhao
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 174:4415-23. 2005
    ..These results strongly support the idea that redirection of normal T cell specificity by TCR gene transfer can have potential applications in tumor adoptive immunotherapy...
  34. pmc Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine
    Cary Hsu
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 175:7226-34. 2005
    ..In the setting of adoptive cell transfer, IL-15-transduced lymphocytes may prolong lymphocyte survival in vivo and could potentially enhance antitumor activity...
  35. pmc B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells
    James N Kochenderfer
    Experimental Transplantation and Immunology Branch, National Cancer Institute NCI, Bethesda, MD 20892, USA
    Blood 119:2709-20. 2012
    ....
  36. pmc IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors
    Sid P Kerkar
    Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1502, USA
    J Clin Invest 121:4746-57. 2011
    ....
  37. pmc Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
    James N Kochenderfer
    Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
    Blood 116:4099-102. 2010
    ..Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326...
  38. doi request reprint Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines
    Timothy L Frankel
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cancer Immunol Immunother 59:1757-69. 2010
    ..This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent...
  39. pmc Lack of specific gamma-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation
    William R Burns
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 114:2888-99. 2009
    ..The use of immunomodulatory adjuvants, eg, vaccination or cytokine therapy, for in vivo T-cell activation may help overcome this metabolic quiescence and thus augment cellular immunotherapy-based cancer therapy...
  40. pmc High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation
    Yangbing Zhao
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Ther 13:151-9. 2006
    ..The results of this study indicate that mRNA electroporation provides a powerful tool to introduce genes into both human and murine primary T lymphocytes...
  41. pmc Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment
    Ling Zhang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Ther 19:751-9. 2011
    ..Notably, this targeted and controlled IL-12 treatment was without toxicity. Taken together, our results suggest that using the NFAT.hIL12.PA2 vector might be a promising approach to enhance adoptive cancer immunotherapy...
  42. doi request reprint Modulating the differentiation status of ex vivo-cultured anti-tumor T cells using cytokine cocktails
    Shicheng Yang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, CRC 3 W 3864, Bethesda, MD, 20892, USA
    Cancer Immunol Immunother 62:727-36. 2013
    ..The methodology that we developed for generating a less-differentiated anti-tumor CD8+ T cells ex vivo may be ideal for the adoptive immunotherapy of cancer...
  43. doi request reprint The position of the AUG start codon in MFG-based γ-retroviral vectors has a dramatic effect on translation-dependent protein expression
    Timothy L Frankel
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    J Gene Med 13:478-86. 2011
    ..Little is known about the impact of variations in start codon location within MFG-based vectors on protein expression...
  44. doi request reprint A TCR targeting the HLA-A*0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer
    Nachimuthu Chinnasamy
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 186:685-96. 2011
    ..On the basis of these results, a clinical trial is planned in which patients bearing a variety of tumor histologies will receive autologous PBLs that have been transduced with this optimized anti-MAGE-A3 TCR...
  45. pmc Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a "modified" step-filtration process for clearance of packaging cells
    Steven A Feldman
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 22:107-15. 2011
    ..To date, this platform has generated five clinical-grade gammaretroviral vector products, four of which are now being used in adoptive cell therapy clinical trials for the treatment of a variety of solid cancers...
  46. pmc Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond
    Cyrille J Cohen
    Surgery Branch, Center for Cancer Research, National Cancer Institute NIH, 10 Center Drive, Bethesda, MD 20892, USA
    Cancer Res 67:3898-903. 2007
    ..Preferential pairing of cysteine-modified receptor chains accounts for these observations, which could have significant implications for the improvement of TCR gene therapy...
  47. pmc T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis
    Maria R Parkhurst
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Ther 19:620-6. 2011
    ..It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy...
  48. pmc Transduction of an HLA-DP4-restricted NY-ESO-1-specific TCR into primary human CD4+ lymphocytes
    Yangbing Zhao
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    J Immunother 29:398-406. 2006
    ..Major histocompatibility complex class II TCR-transduced CD4 T cells provides an alternative source of tumor antigen-specific T cells for adoptive immunotherapy of cancer patients...
  49. pmc Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene
    Cary Hsu
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 109:5168-77. 2007
    ..It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation...
  50. pmc Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes
    Daniel Abate-Daga
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr, Bethesda, MD 20892, USA
    Blood 122:1399-410. 2013
    ..These results contribute to a deeper understanding of the properties of transgenic lymphocytes used to treat human malignancies and may provide a rationale for the development of combination therapies as a method to improve ACT...
  51. pmc Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability
    Cyrille J Cohen
    Surgery Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 1201, USA
    Cancer Res 66:8878-86. 2006
    ..These findings have implications for human TCR gene transfer therapy and may provide new insights into the biology of the TCR/CD3 complex...
  52. pmc Collapse of the tumor stroma is triggered by IL-12 induction of Fas
    Sid P Kerkar
    Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Mol Ther 21:1369-77. 2013
    ....
  53. pmc Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials
    Jeremy L Davis
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Clin Cancer Res 16:5852-61. 2010
    ..We conducted 2 clinical trials in which cancer patients were treated with lymphocytes genetically engineered to express murine T-cell receptors (mTCR) specific for tumor-associated antigens p53 and gp100...
  54. ncbi request reprint Real-time quantitative reverse transcriptase-polymerase chain reaction as a method for determining lentiviral vector titers and measuring transgene expression
    Gregory Lizee
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 14:497-507. 2003
    ....
  55. doi request reprint Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice
    Dhanalakshmi Chinnasamy
    National Cancer Institute, Clinical Research Center, Bethesda, MD, USA
    Clin Cancer Res 18:1672-83. 2012
    ..We investigated the feasibility of delivering the proinflammatory cytokine interleukin (IL)-12 into tumor using T cells genetically engineered to express a chimeric antigen receptor (CAR) against the VEGF receptor-2 (VEGFR-2)...
  56. pmc Inhibition of histone lysine methylation enhances cancer-testis antigen expression in lung cancer cells: implications for adoptive immunotherapy of cancer
    Mahadev Rao
    Section of Thoracic Oncology, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
    Cancer Res 71:4192-204. 2011
    ..Combining DNA-demethylating agents with compounds, such as DZNep, that modulate histone lysine methylation may provide a novel epigenetic strategy to augment cancer-testis gene expression as an adjunct to adoptive cancer immunotherapy...
  57. pmc High-affinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines
    Yangbing Zhao
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 179:5845-54. 2007
    ..Although the biological activity of these two relatively low-affinity TCRs was comparable to wild-type reactivity in CD8(+) T cells, introduction of these TCR dramatically increased the reactivity of CD4(+) T cells to tumor cell lines...
  58. ncbi request reprint Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals
    Richard A Morgan
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 16:1065-74. 2005
    ..Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1+ individuals...
  59. pmc Adoptive cell transfer: a clinical path to effective cancer immunotherapy
    Steven A Rosenberg
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, USA
    Nat Rev Cancer 8:299-308. 2008
    ....
  60. pmc The shedding of CD62L (L-selectin) regulates the acquisition of lytic activity in human tumor reactive T lymphocytes
    Shicheng Yang
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 6:e22560. 2011
    ..The linkage of the shedding of CD62L from the surface of anti-tumor T cells and acquisition of lytic activity, suggests a new function for CD62L in T cell effector functions and anti-tumor activity...
  61. pmc Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice
    Dhanalakshmi Chinnasamy
    Surgery Branch, National Cancer Institute, Clinical Research Center, Bethesda, MD 20892, USA
    Cancer Res 73:3371-80. 2013
    ..The data presented here emphasize the possible beneficial effects of combining antiangiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer...
  62. pmc Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia
    Eric Tran
    Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 210:1125-35. 2013
    ..Moreover, the expression of FAP by multipotent BMSCs may point toward the cellular origins of tumor stromal fibroblasts...
  63. ncbi request reprint Enhanced inhibition of human immunodeficiency virus type 1 replication by novel lentiviral vectors expressing human immunodeficiency virus type 1 envelope antisense RNA
    Mario R Mautino
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10C103, Bethesda, MD 20892 1851, USA
    Hum Gene Ther 13:1027-37. 2002
    ..Our results suggest that higher vector copy number and increased levels of envAS RNA expression contribute to block replication of divergent strains of HIV-1...
  64. pmc Protein L: a novel reagent for the detection of chimeric antigen receptor (CAR) expression by flow cytometry
    Zhili Zheng
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Transl Med 10:29. 2012
    ..Despite the improvements in the design of CARs and expansion of the number of target antigens, there is no universal flow cytometric method available to detect the expression of CARs on the surface of transduced lymphocytes...
  65. pmc Genetic engineering with T cell receptors
    Ling Zhang
    National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892, USA
    Adv Drug Deliv Rev 64:756-62. 2012
    ..In this review, we discuss the progress and prospects of TCR gene-engineered T cells as a therapeutic strategy for treating patients with melanoma and other cancers...
  66. pmc Treating cancer with genetically engineered T cells
    Tristen S Park
    National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892, USA
    Trends Biotechnol 29:550-7. 2011
    ..In this review, we discuss the development of TCR and CAR gene transfer technology and the expansion of these therapies into different cancers with the recent demonstration of the clinical efficacy of these treatments...
  67. ncbi request reprint Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNA-mediated RNA interference
    Natasha J Caplen
    Medical Genetics Branch, National Human Genome Research Institute and Neurogenetics Branch, National Institute of Neurological Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Mol Genet 11:175-84. 2002
    ..This study demonstrates the feasibility of targeting a transcript associated with an important group of genetic diseases by RNAi...
  68. ncbi request reprint Inhibition of viral gene expression and replication in mosquito cells by dsRNA-triggered RNA interference
    Natasha J Caplen
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
    Mol Ther 6:243-51. 2002
    ....
  69. ncbi request reprint Toxicity of a first-generation adenoviral vector in rhesus macaques
    Jay N Lozier
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    Hum Gene Ther 13:113-24. 2002
    ..The rhesus macaque may be a useful animal model in which to evaluate mechanisms of adenovirus toxicities that have been encountered during clinical gene therapy trials...
  70. pmc Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia
    Waleed Haso
    Pediatric Oncology Branch, Center for Cancer Research CCR, National Cancer Institute NCI, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Blood 121:1165-74. 2013
    ..We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL...
  71. doi request reprint Cancer therapy with genetically-modified T cells for the treatment of melanoma
    Kiran H Lagisetty
    National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD, USA
    J Gene Med 14:400-4. 2012
    ..This article is a US Government work and is in the public domain in the USA...
  72. ncbi request reprint High-efficiency lentiviral vector-mediated gene transfer into murine macrophages and activated splenic B lymphocytes
    Gabriela R Rossi
    National Cancer Institute, Building 10, Room 2B04, National Institutes of Health, 10 Center Drive, MSC 1502, Bethesda, MD 20892, USA
    Hum Gene Ther 14:385-91. 2003
    ..We conclude that HIV-1-based lentiviral vectors can mediate efficient gene transfer into primary murine macrophages and mature B lymphocytes...
  73. ncbi request reprint Gene therapy-based treatment for HIV-positive patients with malignancies
    Elizabeth M Kang
    Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA
    J Hematother Stem Cell Res 11:809-16. 2002
    ..Vector-transduced cells remain detectable at low levels more than 3 years post-transplantation, suggesting the potential for gene therapy as a reasonable goal for the treatment of HIV...
  74. ncbi request reprint Gene therapy of HIV-1 infection using lentiviral vectors expressing anti-HIV-1 genes
    Mario R Mautino
    Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    AIDS Patient Care STDS 16:11-26. 2002
    ..This review focuses on the use of lentiviral vectors as the main agents to mediate inhibition of HIV-1 replication and discusses the different genetic intervention strategies for gene therapy of HIV-1 infection...
  75. ncbi request reprint Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome
    Elizabeth M Kang
    Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 99:698-701. 2002
    ..These results suggest that nonmyeloablative allogeneic transplantation in the context of highly active antiretroviral therapy is feasible in patients with treatment-sensitive HIV infection...
  76. ncbi request reprint Sustained phenotypic correction of hemophilia a mice following oncoretroviral-mediated expression of a bioengineered human factor VIII gene in long-term hematopoietic repopulating cells
    Morvarid Moayeri
    Department of Anatomy and Cell Biology, Flow Cytometry Core Facility, The George Washington University Medical Center, Washington, DC 20037, USA
    Mol Ther 10:892-902. 2004
    ..Notably, the hemophilic phenotype of all treated mice was corrected, thus demonstrating the potential of HSC-directed oncoretroviral-mediated factor VIII gene transfer as a curative therapeutic strategy for hemophilia A...
  77. ncbi request reprint Semliki Forest virus vectors for gene transfer
    Jarmo Wahlfors
    A I Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
    Methods Mol Med 76:493-502. 2003
  78. ncbi request reprint Minigene-containing retroviral vectors using an alphavirus/retrovirus hybrid vector system. Production and use
    Jarmo Wahlfors
    A I Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
    Methods Mol Med 69:173-86. 2002
  79. ncbi request reprint Selecting highly affine and well-expressed TCRs for gene therapy of melanoma
    Annelies Jorritsma
    Department of Immunology, The Netherlands Cancer Institute NKI, Amsterdam, The Netherlands
    Blood 110:3564-72. 2007
    ..The procedures described in this study should be of general value for the selection of well- and stably expressed, high-affinity, and safe human TCRs for subsequent clinical testing...