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Genomes and Genes | James L RileySummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
PD-1 signaling in primary T cellsJames L Riley
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, The University of Pennsylvania, Philadelphia, PA, USA
Immunol Rev 229:114-25. 2009..Lastly, we describe models to dissect the function of the PD-1 cytoplasmic tail using primary cells in the absence of agonist antibodies...
Human T regulatory cell therapy: take a billion or so and call me in the morningJames 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...
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanismsRichard V Parry
Abramson Family Cancer Research Institute, 556 BRB II III, 421 Curie Blvd, University of Pennsylvania, Philadelphia, PA 19104, USA
Mol Cell Biol 25:9543-53. 2005..Together, these data suggest that CTLA-4 and PD-1 inhibit T-cell activation through distinct and potentially synergistic mechanisms...
Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cellsRichard 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...
Adoptive immunotherapy: good habits instilled at youth have long-term benefitsChrystal 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...
The inducible costimulator (ICOS) is critical for the development of human T(H)17 cellsChrystal 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...
CD28 costimulation is essential for human T regulatory expansion and functionTatiana 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....
Extensive replicative capacity of human central memory T cellsMarcela 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...
B and T lymphocyte attenuator-mediated signal transduction provides a potent inhibitory signal to primary human CD4 T cells that can be initiated by multiple phosphotyrosine motifsJens 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 176:6603-14. 2006..These studies question whether SHP-1 or SHP-2 have any role in BTLA function and caution against the use of pervanadate as means to initiate signal transduction cascades in primary cells...
Genetic engineering of T cells for adoptive immunotherapyAngel 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...
Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytesQunrui 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...
TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patientsKatia 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..The results support the feasibility of therapeutic vaccination of ovarian cancer patients...
Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivoMichael 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...
Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demandDaniel E Bauer
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
FASEB J 18:1303-5. 2004..These data suggest that the high rate of glycolysis observed in response to growth factor stimulation is a primary effect rather than a homeostatic response to increased cell growth...
A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term growth of CD4 T lymphocytesAnna 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...
HIV sequence variation associated with env antisense adoptive T-cell therapy in the hNSG mouse modelRithun Mukherjee
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Mol Ther 18:803-11. 2010..Unexpectedly, this enrichment was only detected after the challenge with HIV-1(BaL), where the viral genome would form an imperfect duplex with envAS, and not HIV-1(NL4-3), where a perfectly matched duplex would form...
Ligation of CD28 by its natural ligand CD86 in the absence of TCR stimulation induces lipid raft polarization in human CD4 T cellsBirgit Kovacs
Division of Rheumatology, Children s Hospital of Philadelphia, and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Immunol 175:7848-54. 2005..This result has implications for mechanisms of T cell activation. Abnormalities in this process may alter T and B cell tolerance and susceptibility to infection...
FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune diseaseBin Li
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 252 John Morgan Building, 36th and Hamilton Walk, Philadelphia, PA 19104 6082, USA
Int Immunol 19:825-35. 2007..This study explains some features of the pathogenesis of a disease syndrome that arises as a consequence of specific assembly failure of a transcriptional repressor due to certain mutations within the FOXP3 leucine zipper...
Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory moleculesMegan 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...
Retinoic acid and rapamycin differentially affect and synergistically promote the ex vivo expansion of natural human T regulatory cellsTatiana N Golovina
Department of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
PLoS ONE 6:e15868. 2011..We conclude that while the use of ATRA as a single agent to expand Tregs for human therapy is not warranted, its use in combination with rapamycin may have benefit...
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 activationJens 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...
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 lymphocytesRichard 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...
The CD28 family: a T-cell rheostat for therapeutic control of T-cell activationJames 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....
Decade-long safety and function of retroviral-modified chimeric antigen receptor T cellsJohn 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...
Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ TregsTatiana Akimova
Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104 4318, USA
Clin Immunol 136:348-63. 2010..Hence, HDACi compounds are promising pharmacologic tools to increase Treg suppressive functions, and this action may potentially be of use in patients with autoimmunity or post-transplantation...
Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domainsCarmine 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...
Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptorAngel 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....
Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptorsJames 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...
Human CD8+ T cells do not require the polarization of lipid rafts for activation and proliferationBirgit 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...
Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptorEdmund 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...
Engineering lymphocyte subsets: tools, trials and tribulationsCarl 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....
The paracaspase MALT1 controls caspase-8 activation during lymphocyte proliferationHolli Kawadler
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Mol Cell 31:415-21. 2008..Our results reveal a mechanism that utilizes a protease potentially deadly to the cell for proliferative signaling and demonstrate a functional connection between the caspase and paracaspase families to enable nonapoptotic processes...
Kruppel-like factor 2 modulates CCR5 expression and susceptibility to HIV-1 infectionMax W Richardson
Department of Microbiology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 189:3815-21. 2012..Thus, KLF2 is a host factor that modulates CCR5 expression in CD4 T cells and influences susceptibility to R5 infection...
TCR affinity and specificity requirements for human regulatory T-cell functionGabriela Plesa
Department of Microbiology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
Blood 119:3420-30. 2012..These studies underscore the clinical utility of using MHC class I-restricted TCRs to endow Tregs with specificity to control autoimmune disease and highlight the conditions in which this approach would have most therapeutic benefit...
HLA tetramer-based artificial antigen-presenting cells for stimulation of CD4+ T cellsMarcela 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...
Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycinSamik 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...
Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiationElizabeth 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...
The road to recovery: translating PD-1 biology into clinical benefitJames 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...
FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repressionBin Li
Department of Pathology and Laboratory Medicine, University of Pennsylvania, 36th and Hamilton Walk, Philadelphia, PA 19104 6082, USA
Proc Natl Acad Sci U S A 104:4571-6. 2007..These findings identify a previously uncharacterized complex-based mechanism by which FOXP3 actively mediates transcriptional repression...
Mode of transmission affects the sensitivity of human immunodeficiency virus type 1 to restriction by rhesus TRIM5alphaMax W Richardson
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
J Virol 82:11117-28. 2008..These studies further define the role of rhTRIM5alpha in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5alpha in anti-HIV therapy...
Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferationEdward 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...
Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infectionGraham Simmons
Department of Microbiology. Abramson Family Cancer Research Institute, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA
J Virol 77:13433-8. 2003..Finally, a panel of ligands to and soluble analogues of FRalpha were unable to inhibit infection on a range of cell lines, questioning the role of FRalpha as an important factor for Ebola virus entry...
Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5Dawn 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...
CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patientsAndrew J Rech
Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Sci Transl Med 4:134ra62. 2012..We conclude that CD25 blockade depletes and selectively reprograms T(regs) in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated T(regs) while avoiding autoimmunity...
Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BBMarcela 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...
The CD28 signaling pathway regulates glucose metabolismKenneth 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...
Addition of deoxynucleosides enhances human immunodeficiency virus type 1 integration and 2LTR formation in resting CD4+ T cellsGabriela 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...
Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleasesElena 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...
