Carl H June

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. doi Remote Controlled CARs: Towards a Safer Therapy for Leukemia
    Carl H June
    Parker Institute for Cancer Immunotherapy at the University of Pennsylvania
    Cancer Immunol Res 4:643. 2016
  2. doi Adoptive cellular therapy: a race to the finish line
    Carl H June
    Center for Cellular Immunotherapies and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Sci Transl Med 7:280ps7. 2015
  3. pmc T cell engineering as therapy for cancer and HIV: our synthetic future
    Carl H June
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104 5156, USA Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104 5156, USA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Philos Trans R Soc Lond B Biol Sci 370:20140374. 2015
  4. pmc Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts
    Masasuke Ohno
    Brain Tumor Program, University of Pittsburgh Cancer Institute, 1 19e Research Pavilion at the Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    J Immunother Cancer 1:21. 2013
  5. pmc Engineered T cells for cancer therapy
    Carl H June
    Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Boulevard, 8th Floor, Philadelphia, PA, 19104 5156, USA
    Cancer Immunol Immunother 63:969-75. 2014
  6. pmc IL-21 promotes the expansion of CD27+ CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells
    Saskia J A M Santegoets
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    J Transl Med 11:37. 2013
  7. pmc Defining the critical hurdles in cancer immunotherapy
    Bernard A Fox
    Earle A, Chiles Research Institute, Robert W, Franz Research Center, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
    J Transl Med 9:214. 2011
  8. pmc Engineering lymphocyte subsets: tools, trials and tribulations
    Carl H June
    Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nat Rev Immunol 9:704-16. 2009
  9. ncbi A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses
    Daniel H Sterman
    Thoracic Oncology Gene Therapy Program and Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104 4283, USA
    Clin Cancer Res 13:4456-66. 2007
  10. pmc Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells
    Richard G Carroll
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS ONE 3:e3289. 2008

Detail Information

Publications94

  1. doi Remote Controlled CARs: Towards a Safer Therapy for Leukemia
    Carl H June
    Parker Institute for Cancer Immunotherapy at the University of Pennsylvania
    Cancer Immunol Res 4:643. 2016
    ..An article in Cancer Immunology Research presents an approach to circumvent this issue. Cancer Immunol Res; 4(8); 643. ©2016 AACRSee article by Sakemura et al., p. 658. ..
  2. doi Adoptive cellular therapy: a race to the finish line
    Carl H June
    Center for Cellular Immunotherapies and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Sci Transl Med 7:280ps7. 2015
    ..Here, we discuss some of the challenges--such as regulatory, cost, and manufacturing--and opportunities, including personalized gene-modified T cells, that face the field of adoptive cellular therapy...
  3. pmc T cell engineering as therapy for cancer and HIV: our synthetic future
    Carl H June
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104 5156, USA Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104 5156, USA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Philos Trans R Soc Lond B Biol Sci 370:20140374. 2015
    ..Many questions remain in the field of engineered T cells, but the encouraging response rates pave a wide road for future investigation into fields as diverse as cancer and chronic infections. ..
  4. pmc Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts
    Masasuke Ohno
    Brain Tumor Program, University of Pittsburgh Cancer Institute, 1 19e Research Pavilion at the Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    J Immunother Cancer 1:21. 2013
    ..We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM...
  5. pmc Engineered T cells for cancer therapy
    Carl H June
    Abramson Cancer Center, University of Pennsylvania, 3400 Civic Center Boulevard, 8th Floor, Philadelphia, PA, 19104 5156, USA
    Cancer Immunol Immunother 63:969-75. 2014
    ....
  6. pmc IL-21 promotes the expansion of CD27+ CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells
    Saskia J A M Santegoets
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    J Transl Med 11:37. 2013
    ..Here, we have compared the effects of IL-2, -15 and -21 cytokines on the expansion and activation of TIL from single-cell suspensions of non-small cell lung cancer, ovarian cancer and melanoma...
  7. pmc Defining the critical hurdles in cancer immunotherapy
    Bernard A Fox
    Earle A, Chiles Research Institute, Robert W, Franz Research Center, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
    J Transl Med 9:214. 2011
    ..Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer...
  8. pmc Engineering lymphocyte subsets: tools, trials and tribulations
    Carl H June
    Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Nat Rev Immunol 9:704-16. 2009
    ....
  9. ncbi A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses
    Daniel H Sterman
    Thoracic Oncology Gene Therapy Program and Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104 4283, USA
    Clin Cancer Res 13:4456-66. 2007
    ..IFN-beta) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE)...
  10. pmc Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells
    Richard G Carroll
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS ONE 3:e3289. 2008
    ..These preclinical data suggest that human IL-18 may have use as an adjuvant for immune reconstitution after cytotoxic therapies, and to augment adoptive immunotherapy, donor leukocyte infusions, and vaccine strategies...
  11. pmc A trial of intrapleural adenoviral-mediated Interferon-α2b gene transfer for malignant pleural mesothelioma
    Daniel H Sterman
    Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104 4283, USA
    Am J Respir Crit Care Med 184:1395-9. 2011
    ..Clinical trial registered with www.clinicaltrials.gov (NCT 01212367)...
  12. pmc Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy
    Ioannis Alagkiozidis
    Ovarian Cancer Research Center, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Transl Med 9:77. 2011
    ..Here, we investigated the potential use of anticancer chemotherapeutic drugs in combination with IL-18, a cytokine with strong immunostimulatory properties...
  13. doi Phase I/II randomized trial of dendritic cell vaccination with or without cyclophosphamide for consolidation therapy of advanced ovarian cancer in first or second remission
    Christina S Chu
    Department of Obstetrics and Gynecology and Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cancer Immunol Immunother 61:629-41. 2012
    ..In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Immunotherapy may have potential for consolidation therapy...
  14. pmc Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo
    Michael C Milone
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 5160, USA
    Mol Ther 17:1453-64. 2009
    ..Together these results suggest that incorporation of the CD137 signaling domain in CARs should improve the persistence of CARs in the hematologic malignancies and hence maximize their antitumor activity...
  15. pmc Treatment of advanced leukemia in mice with mRNA engineered T cells
    David M Barrett
    Division of Oncology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Hum Gene Ther 22:1575-86. 2011
    ..RNA CARs are a genetic engineering approach that should not be subject to genotoxicity, and they provide a platform for rapidly optimizing CAR design before proceeding to more costly and laborious stable expression systems...
  16. pmc Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor
    Yangbing Zhao
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine and Thoracic Oncology Research Laboratory and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    Cancer Res 70:9053-61. 2010
    ..This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors...
  17. doi The inducible costimulator (ICOS) is critical for the development of human T(H)17 cells
    Chrystal M Paulos
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Sci Transl Med 2:55ra78. 2010
    ..These findings have provided the rationale for designing new clinical trials for tumor immunotherapy...
  18. pmc A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions
    Daniel H Sterman
    Section of Interventional Pulmonology and Thoracic Oncology, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104 4283, USA
    Mol Ther 18:852-60. 2010
    ..This approach was safe, induced immune responses and disease stability. However, rapid development of Nabs prevented effective gene transfer after the second dose, even with a dose interval as short as 7 days...
  19. pmc Adoptive immunotherapy: good habits instilled at youth have long-term benefits
    Chrystal M Paulos
    Abramson Family Cancer Research Institute, University of Pennsylvania, BRB II III, Room 554, 421 Curie Boulevard, Philadelphia, PA, 19104 6160, USA
    Immunol Res 42:182-96. 2008
    ..We also describe how aAPCs can be used to broaden ACT to treat patients with a wide variety of cancers, chronic infectious diseases, and autoimmune manifestations...
  20. ncbi Extensive replicative capacity of human central memory T cells
    Marcela V Maus
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 172:6675-83. 2004
    ..In conclusion, aAPCs expand T(CM) that have extensive replicative capacity, and have potential applications in adoptive immunotherapy as well as for studying the biology of human MHC class II-restricted T cells...
  21. ncbi TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients
    Katia Schlienger
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Cancer Res 9:1517-27. 2003
    ..We also sought to measure preexisting antitumor immunity in patients with advanced ovarian cancer...
  22. pmc CD28 costimulation is essential for human T regulatory expansion and function
    Tatiana N Golovina
    Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 181:2855-68. 2008
    ....
  23. pmc Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5
    Dawn A Maier
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
    Hum Gene Ther 24:245-58. 2013
    ..Based on these findings, we initiated a clinical trial testing the safety and feasibility of CCR5 gene-edited CD4+ T-cell transfer in study subjects with HIV-1 infection...
  24. pmc Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules
    Megan M Suhoski
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104 5160, USA
    Mol Ther 15:981-8. 2007
    ..Finally, the aAPCs provide an efficient platform to expand genetically modified T cells and to maintain CD28 expression on CD8 T cells. Therefore, K562-based aAPCs have therapeutic potential for adoptive immunotherapies and vaccinations...
  25. pmc Genetic engineering of T cells for adoptive immunotherapy
    Angel Varela-Rohena
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Blvd 556 BRB II III, Philadelphia, PA, 19104, USA
    Immunol Res 42:166-81. 2008
    ..In this article, we focus on strategies to (1) dissect the signals controlling T cell proliferation; (2) render CD4 T cells resistant to HIV-1 infection; and (3) redirect CD8 T cell antigen specificity...
  26. doi Pilot study of prophylactic ex vivo costimulated donor leukocyte infusion after reduced-intensity conditioned allogeneic stem cell transplantation
    Anita J Kumar
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
    Biol Blood Marrow Transplant 19:1094-101. 2013
    ..Relapse remains the major cause of treatment failure after RIC HSCT even with rapid withdrawal of immune suppression and the use of prophylactic aDLI, and better strategies to prevent relapse are needed...
  27. pmc T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia
    Michael Kalos
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sci Transl Med 3:95ra73. 2011
    ....
  28. pmc Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes
    Qunrui Ye
    Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Transl Med 9:131. 2011
    ..Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application...
  29. ncbi Development of novel substrates for tumor immunotherapy
    Waleed S W Shalaby
    Division of Gynecologic Oncology, University of Pennsylvania Medical Center, 3400 Spruce Street, First Floor Dulles, Suite 1000 Courtyard, Philadelphia, PA 19104, USA
    J Control Release 91:209-24. 2003
    ..The regression model showed complete tumor regression in four of seven animals and stable disease in three of seven. In the latter study, a dramatic level of DC infiltration was observed compared to controls...
  30. pmc Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor
    Edmund K Moon
    Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    Clin Cancer Res 17:4719-30. 2011
    ..Adoptive T-cell immunotherapy with tumor infiltrating lymphocytes or genetically-modified T cells has yielded dramatic results in some cancers. However, T cells need to traffic properly into tumors to adequately exert therapeutic effects...
  31. pmc Adoptive T cell therapy for cancer in the clinic
    Carl H June
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Clin Invest 117:1466-76. 2007
    ..Improved molecular biology techniques have also increased enthusiasm and feasibility for testing genetically engineered T cells. The current status of the field and prospects for clinical translation are reviewed herein...
  32. pmc Enhanced function of redirected human T cells expressing linker for activation of T cells that is resistant to ubiquitylation
    Naoki Kunii
    Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Hum Gene Ther 24:27-37. 2013
    ..These results indicate that interruption of LAT ubiquitylation is a promising strategy to augment effector T cell function for adoptive cell therapy...
  33. pmc Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia
    David L Porter
    Abramson Cancer Center, and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
    N Engl J Med 365:725-33. 2011
    ..Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect...
  34. ncbi A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term growth of CD4 T lymphocytes
    Anna K Thomas
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Immunol 105:259-72. 2002
    ..We conclude that K32 aAPCs are a robust system for clinical scale ex vivo expansion of CD4 T cells...
  35. pmc Post-transplant adoptive T-cell immunotherapy
    Nicole A Aqui
    Abramson Family Cancer Research Institute and the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 1416, USA
    Best Pract Res Clin Haematol 21:503-19. 2008
    ..This chapter will discuss the challenges that face the field before adoptive T-cell therapy can be translated into routine clinical practice...
  36. pmc Regimen-specific effects of RNA-modified chimeric antigen receptor T cells in mice with advanced leukemia
    David M Barrett
    Division of Oncology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Hum Gene Ther 24:717-27. 2013
    ....
  37. doi Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells
    Omkar U Kawalekar
    Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Immunity 44:380-90. 2016
    ..These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies. ..
  38. pmc T cells expressing chimeric antigen receptors can cause anaphylaxis in humans
    Marcela V Maus
    Abramson Cancer Center MVM, ARH, GLB, SMA, BLL, YZ, MK, CHJ, the Department of Medicine MVM, ARH, GLB, SMA and the Department of Pathology and Laboratory Medicine BLL, XL, YZ, CHJ and MK, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104
    Cancer Immunol Res 1:26-31. 2013
    ..These results indicate that the potential immunogenicity of CARs derived from murine antibodies may be a safety issue for mRNA CARs, especially when administered using an intermittent dosing schedule...
  39. doi Immunotherapy opportunities in ovarian cancer
    Christina S Chu
    University of Pennsylvania, Division of Gynecologic Oncology, Center for Research on Ovarian Cancer, PA, USA
    Expert Rev Anticancer Ther 8:243-57. 2008
    ..Additional combinatorial approaches include the use of cytokines and/or chemotherapy with immune therapy...
  40. pmc Programming the next generation of dendritic cells
    Richard G Carroll
    Abramson Family Research Cancer Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Mol Ther 15:846-8. 2007
  41. pmc Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV
    Pablo Tebas
    Department of Medicine and Center for AIDS Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    Blood 121:1524-33. 2013
    ..We conclude that gene-modified T cells have the potential to decrease the fitness of HIV-1 and conditionally replicative lentiviral vectors have a promising safety profile in T cells...
  42. ncbi A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation
    David L Porter
    Stem Cell Transplant Program, Division of Hematology Oncology, 16 Penn Tower, 3400 Spruce St, Philadelphia, PA 19104, USA
    Blood 107:1325-31. 2006
    ..Adoptive transfer of costimulated activated allogeneic T cells is feasible, does not result in excessive GVHD, and may contribute to durable remissions in diseases where conventional DLI has been disappointing...
  43. ncbi Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation
    Edward Y Woo
    Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    J Immunol 168:4272-6. 2002
    ..Together these results suggest that the CD4(+)CD25(+) T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer...
  44. pmc Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells
    John Scholler
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 6076, USA
    Sci Transl Med 4:132ra53. 2012
    ..Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases...
  45. doi Measuring IL-6 and sIL-6R in serum from patients treated with tocilizumab and/or siltuximab following CAR T cell therapy
    Fang Chen
    University of Pennsylvania, Department of Pathology and Laboratory Medicine, Product Development and Correlative Sciences Laboratory, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, United States
    J Immunol Methods 434:1-8. 2016
    ....
  46. pmc A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors
    Xiaojun Liu
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
    Cancer Res 76:1578-90. 2016
    ....
  47. ncbi The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation
    James L Riley
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Blood 105:13-21. 2005
    ....
  48. ncbi CD28 and inducible costimulatory protein Src homology 2 binding domains show distinct regulation of phosphatidylinositol 3-kinase, Bcl-xL, and IL-2 expression in primary human CD4 T lymphocytes
    Richard V Parry
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 171:166-74. 2003
    ..Thus, differences within their respective SH2 binding domains explain, at least in part, the distinct regulation of IL-2 and Bcl-x(L) expression following ICOS- or CD28-mediated costimulation...
  49. ncbi Regulatory T cells and cytokines in malignant pleural effusions secondary to mesothelioma and carcinoma
    Peter DeLong
    Thoracic Oncology Research Laboratory, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 4:342-6. 2005
    ..These results have implications for the development of immunotherapy directed to the malignant pleural space, and suggest the need to tailor immunotherapy to overcome immunosuppressive mechanisms in tumor environments...
  50. pmc Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains
    Carmine Carpenito
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:3360-5. 2009
    ..Genetically redirected T cells have promise of targeting T lymphocytes to tumor antigens, confer resistance to the tumor microenvironment, and providing immunosurveillance...
  51. pmc Human T regulatory cell therapy: take a billion or so and call me in the morning
    James L Riley
    Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Immunity 30:656-65. 2009
    ..This review will focus on the preclinical models that provide the rationale for current trials and it will address both the challenges and opportunities in human Treg cell therapy...
  52. doi T cells expressing chimeric antigen receptors can cause anaphylaxis in humans
    Marcela V Maus
    Authors Affiliations Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
    Cancer Immunol Res 1:26-31. 2013
    ..These results indicate that the potential immunogenicity of CARs derived from murine antibodies may be a safety issue for mRNA CARs, especially when administered using an intermittent dosing schedule...
  53. pmc Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies
    Gregory L Beatty
    Abramson Cancer Center University of Pennsylvania, Philadelphia, PA Division of Hematology Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
    Cancer Immunol Res 2:112-20. 2014
    ..Thus, these findings support the development of mRNA CAR-based strategies for carcinoma and other solid tumors. ..
  54. pmc Chimeric antigen receptor-modified T cells for acute lymphoid leukemia
    Stephan A Grupp
    Children s Hospital of Philadelphia, Philadelphia, PA 19104 4318, USA
    N Engl J Med 368:1509-18. 2013
    ..The emergence of tumor cells that no longer express the target indicates a need to target other molecules in addition to CD19 in some patients with ALL...
  55. pmc Analysis of lentiviral vector integration in HIV+ study subjects receiving autologous infusions of gene modified CD4+ T cells
    Gary P Wang
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6076, USA
    Mol Ther 17:844-50. 2009
    ....
  56. ncbi Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB
    Marcela V Maus
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA
    Nat Biotechnol 20:143-8. 2002
    ..Furthermore, apoptosis of cultured CD8(+) T cells was diminished by this approach. This approach may have important therapeutic implications for adoptive immunotherapy...
  57. doi Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment
    Elizabeth O Hexner
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
    Am J Hematol 91:453-60. 2016
    ..Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD...
  58. ncbi Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation
    Elizabeth O Hexner
    Division of Hematology Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biol Blood Marrow Transplant 13:1135-44. 2007
    ..CD3/CD28 costimulation of UCB T cells represents a potential strategy for enhancing the engraftment of UCB...
  59. pmc Fibroblast activation protein expression by stromal cells and tumor-associated macrophages in human breast cancer
    Julia Tchou
    Division of Endocrine and Oncologic Surgery, Department of Surgery, and the Rena Rowan Breast Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Electronic address
    Hum Pathol 44:2549-57. 2013
    ..More work is needed to explore the role of FAP as a potential targetable molecule in breast cancer treatment. ..
  60. ncbi Interferon beta adenoviral gene therapy in a patient with ovarian cancer
    Daniel H Sterman
    Thoracic Oncology Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA
    Nat Clin Pract Oncol 3:633-9. 2006
    ..Diagnosis Stage IV ovarian cancer with malignant ascites and pleural effusion. Management Tunneled pleural catheter and intrapleural adenoviral-mediated interferon beta gene therapy...
  61. pmc Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases
    Matthew J Riese
    Divisions of Hematology Oncology, Pulmonology, and Rheumatology, Departments of Medicine, and Path and Lab Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Cancer Res 73:3566-77. 2013
    ..These results suggest that deletion of negative regulators of TCR signaling enhances the activity and function of CAR-expressing T cells and identify dgks as potential targets for improving the clinical potential of CARs...
  62. ncbi SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation
    Jens M Chemnitz
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 173:945-54. 2004
    ..Despite this interaction, the ability of PD-1 to block T cell activation required receptor ligation, suggesting that colocalization of PD-1 with CD3 and/or CD28 may be necessary for inhibition of T cell activation...
  63. pmc Human CD8+ T cells do not require the polarization of lipid rafts for activation and proliferation
    Birgit Kovacs
    Division of Rheumatology, Department of Pediatrics, Children s Hospital of Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 99:15006-11. 2002
    ..It is possible that the lower stringency of CD8(+) T cell activation obviates a requirement for raft polarization...
  64. pmc Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors
    James L Riley
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Proc Natl Acad Sci U S A 99:11790-5. 2002
    ..Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement selectively blocked augmentation of gene regulations by CD28-mediated costimulation, but did not ablate gene regulation induced by TCR triggering alone...
  65. pmc Mesothelin, a novel immunotherapy target for triple negative breast cancer
    Julia Tchou
    Division of Endocrine and Oncologic Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 1693, USA
    Breast Cancer Res Treat 133:799-804. 2012
    ..7 vs. 8.7 %, p < 0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date...
  66. pmc Putting the brakes on BTLA in T cell-mediated cancer immunotherapy
    Chrystal M Paulos
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104 6160, USA
    J Clin Invest 120:76-80. 2010
    ..We discuss these findings in the context of the expanding field of cosignaling molecules and their implications for T cell-based therapies for cancer...
  67. pmc Transfer of influenza vaccine-primed costimulated autologous T cells after stem cell transplantation for multiple myeloma leads to reconstitution of influenza immunity: results of a randomized clinical trial
    Edward A Stadtmauer
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
    Blood 117:63-71. 2011
    ..The provision of a primed autologous T-cell product significantly improved subsequent influenza vaccine responses. This trial was registered at www.clinicaltrials.gov as #NCT00499577...
  68. pmc Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18
    Ioannis Alagkiozidis
    Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Transl Med 7:104. 2009
    ..Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated...
  69. pmc Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor
    Angel Varela-Rohena
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    Nat Med 14:1390-5. 2008
    ....
  70. pmc Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling
    David M Barrett
    Department of Pediatrics, Division of Oncology, Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Blood 118:e112-7. 2011
    ....
  71. pmc Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia
    Joseph A Fraietta
    Center for Cellular Immunotherapies and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
    Blood 127:1117-27. 2016
    ..Our studies demonstrate that improved T-cell function may also contribute to the efficacy of ibrutinib in CLL. These trials were registered at www.clinicaltrials.gov as #NCT01747486, #NCT01105247, and #NCT01217749. ..
  72. ncbi HLA tetramer-based artificial antigen-presenting cells for stimulation of CD4+ T cells
    Marcela V Maus
    Abramson Family Cancer Research Institute, 557 BRB II III, 421 Curie Boulevard, University of Pennsylvania, Philadelphia 19104, USA
    Clin Immunol 106:16-22. 2003
    ..We find that an indirect coating of HLA-peptide tetramers on beads via an anti-Class II antibody provides specific stimulation of antigen-specific CD4(+) T cells...
  73. pmc Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection
    Chuka A Didigu
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA
    Blood 123:61-9. 2014
    ..These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections. ..
  74. pmc Radiation and immunotherapy: a synergistic combination
    Anusha Kalbasi
    Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 123:2756-63. 2013
    ..Preclinical data indicate that RT can potentiate the systemic efficacy of immunotherapy, while activation of the innate and adaptive immune system can enhance the local efficacy of RT. ..
  75. pmc In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB)
    De Gang Song
    Ovarian Cancer Research Center, Department of Obstetrics and Gynecology and Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 71:4617-27. 2011
    ....
  76. ncbi Adoptive immunotherapy: new ways to skin the cat?
    Michael C Milone
    Abramson Family Cancer Research Institute and the Department of Pathology and Laboratory Medicine, University of Pennsylvania, PA 19104, USA
    Clin Immunol 117:101-3. 2005
  77. ncbi Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation
    Ginna G Laport
    Translational Research Program, Abramsonm Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
    Blood 102:2004-13. 2003
    ....
  78. ncbi A translational bridge to cancer immunotherapy: exploiting costimulation and target antigens for active and passive T cell immunotherapy
    Robert H Vonderheide
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center and the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Immunol Res 27:341-56. 2003
    ..Phase I trials translating these discoveries to novel active and passive T cell therapies have been initiated, with an eye toward combining these strategies once safety is established...
  79. pmc Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology
    Michael Kalos
    Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5156, USA
    Immunity 39:49-60. 2013
    ..As the field of adoptive transfer technology matures, the major engineering challenge is the development of automated cell culture systems, so that the approach can extend beyond specialized academic centers and become widely available. ..
  80. pmc Chimeric antigen receptor therapy for cancer
    David M Barrett
    Abramson Cancer Center and the Departments of Medicine, Pediatrics, and Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 email
    Annu Rev Med 65:333-47. 2014
    ..The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of cancer. ..
  81. ncbi Clinical application of expanded CD4+25+ cells
    Carl H June
    The Abramson Family Cancer Research Institute, The Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Semin Immunol 18:78-88. 2006
    ....
  82. ncbi Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection
    Bruce L Levine
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, USA
    Nat Med 8:47-53. 2002
    ....
  83. ncbi The road to recovery: translating PD-1 biology into clinical benefit
    James L Riley
    Abramson Family Research Cancer Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Trends Immunol 28:48-50. 2007
    ..Here, we discuss impending issues in the translation to clinical studies in light of recent adverse events with costimulatory antibody therapy...
  84. ncbi Tumor-associated macrophages as a source of functional dendritic cells in ovarian cancer patients
    Christina S Chu
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Immunol 102:291-301. 2002
    ..Therefore, TAMs have potential use for either ex vivo or in vivo DC-based immunotherapy, particularly in individuals in which more conventional sources of DCs have been depleted...
  85. doi Adoptive cellular therapy
    Stephan A Grupp
    Division of Oncology and Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Curr Top Microbiol Immunol 344:149-72. 2011
    ..This chapter focuses on various applications of ACT for cancer immunotherapy, and we discuss some of the latest progress and hurdles in translating these technologies to the clinic...
  86. pmc Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
    Elena E Perez
    Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, 421 Curie Blvd, Room 554, BRB II III, Philadelphia, Pennsylvania 19104 6160, USA
    Nat Biotechnol 26:808-16. 2008
    ..Thus adoptive transfer of ex vivo expanded CCR5 ZFN-modified autologous CD4(+) T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection...
  87. ncbi The CD28 signaling pathway regulates glucose metabolism
    Kenneth A Frauwirth
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Immunity 16:769-77. 2002
    ..These data suggest that CD28 costimulation functions to increase glycolytic flux, allowing T cells to anticipate energetic and biosynthetic needs associated with a sustained response...
  88. pmc Gene transfer in humans using a conditionally replicating lentiviral vector
    Bruce L Levine
    Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:17372-7. 2006
    ..There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans...
  89. pmc Zoom Zoom: racing CARs for multiple myeloma
    Marcela V Maus
    Translational Research Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Cancer Res 19:1917-9. 2013
    ..B-cell maturation antigen (BCMA) is expressed only on mature B cells and plasma cells and promotes their survival. BCMA is a promising target for CAR-T cells in multiple myeloma...
  90. pmc Principles of adoptive T cell cancer therapy
    Carl H June
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    J Clin Invest 117:1204-12. 2007
    ..Challenges that face the field and must be addressed before adoptive T cell therapy can be translated into routine clinical practice are discussed...
  91. pmc Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin
    Samik Basu
    Abramson Family Cancer Research Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    J Immunol 180:5794-8. 2008
    ..Together, these results indicate that Tregs are programmed to be resistant to rapamycin, providing further rationale for why this immunosuppressive drug should be used in conjunction with expanded Tregs...
  92. pmc Addition of deoxynucleosides enhances human immunodeficiency virus type 1 integration and 2LTR formation in resting CD4+ T cells
    Gabriela Plesa
    Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Virol 81:13938-42. 2007
    ..Thus, deoxynucleoside addition partially overcomes the restriction to HIV infection in resting CD4+ T cells...
  93. ncbi Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling
    Natalie A Christian
    School of Engineering and Applied Science, Department of Bioengineering, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Bioconjug Chem 18:31-40. 2007
    ..7 +/- 0.1 fmol of NIR fluorophore. Our studies will enable future in vivo tracking of ex vivo labeled DCs by NIR fluorescence based imaging...
  94. doi Measurement of intracellular ions by flow cytometry
    Carl H June
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Curr Protoc Immunol . 2004
    ....