Generation of EBV-specific cytotoxic T cells that are resistant to calcineurin inhibitors for the treatment of posttransplantation lymphoproliferative disease.

Abstract:

:Epstein-Barr virus (EBV)-driven posttransplantation lymphoproliferative disease (PTLD) is a serious complication of immunosuppression after either stem cell transplantation (SCT) or solid organ transplantation (SOT). Adoptive transfer of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) is an effective prophylaxis and treatment for PTLD after SCT, but not for PTLD after SOT when pharmacologic immunosuppression cannot be discontinued. We report the generation of calcineurin (CN) mutants that render EBV-CTL resistant to the immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA): mutant CNa12 confers resistance to CsA but not FK506, and mutant CNa22 confers resistance to FK506 but not CsA, whereas mutant CNb30 renders CTLs resistant to both calcineurin inhibitors. Untransduced EBV-CTLs do not proliferate in the presence of FK506/CsA. However, EBV-CTLs transduced with a retroviral vector coding for these mutants retain the ability to both proliferate and secrete normal levels of interferon-gamma in the presence therapeutic levels of FK506 (CNa12), CsA (CNa22), or both (CNb30). The cytotoxicity and phenotype of EBV-CTL lines were unaffected by expression of these mutant CNs. This approach should allow effective immunotherapy with EBV-CTLs in the SOT setting without risking the graft by reduction in immunosuppression, and represents a generic approach to improving immunotherapy in the face of immunosuppression.

journal_name

Blood

journal_title

Blood

authors

Brewin J,Mancao C,Straathof K,Karlsson H,Samarasinghe S,Amrolia PJ,Pule M

doi

10.1182/blood-2009-07-228387

subject

Has Abstract

pub_date

2009-11-26 00:00:00

pages

4792-803

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2009-07-228387

journal_volume

114

pub_type

杂志文章

相关文献

BLOOD文献大全
  • The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells.

    abstract::Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identifi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-10-3458

    authors: Tang DC,Zhu J,Liu W,Chin K,Sun J,Chen L,Hanover JA,Rodgers GP

    更新日期:2005-11-01 00:00:00

  • Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope.

    abstract::Approximately 25% of patients with hemophilia A develop inhibitory antibodies after treatment with factor VIII. Most of the inhibitory activity is directed against epitopes in the A2 and C2 domains. Anti-A2 inhibitory antibodies recognize a 25-residue segment bounded by R484-I508. Several antigenic residues in this se...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-11-3891

    authors: Parker ET,Healey JF,Barrow RT,Craddock HN,Lollar P

    更新日期:2004-08-01 00:00:00

  • How I treat acquired aplastic anemia.

    abstract::Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive biologics and drugs, and supportive care. However, management of SAA patients remains challenging, both acutely in addressing the immediate consequences...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2011-12-274019

    authors: Scheinberg P,Young NS

    更新日期:2012-08-09 00:00:00

  • Follicular helper T-cell-related lymphomas.

    abstract::In this issue of Blood, Wang et al describe the occurrence and pathogenetic relevance of IDH2R172 mutations in angioimmunoblastic T-cell lymphoma (AITL). ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2015-08-665075

    authors: Pileri SA

    更新日期:2015-10-08 00:00:00

  • Retention of B-cell-specific monoclonal antibodies by human lymphoma cells.

    abstract::The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Press OW,Howell-Clark J,Anderson S,Bernstein I

    更新日期:1994-03-01 00:00:00

  • Whole genome scanning as a cytogenetic tool in hematologic malignancies.

    abstract::Over the years, methods of cytogenetic analysis evolved and became part of routine laboratory testing, providing valuable diagnostic and prognostic information in hematologic disorders. Karyotypic aberrations contribute to the understanding of the molecular pathogenesis of disease and thereby to rational application o...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2008-02-130435

    authors: Maciejewski JP,Mufti GJ

    更新日期:2008-08-15 00:00:00

  • Activation of human plasminogen by staphylokinase. Direct evidence that preformed plasmin is necessary for activation to occur.

    abstract::To directly determine whether the mechanism of activation of human plasminogen (HPg) by staphylokinase (Sak) required formation of an active complex of Sak and HPg, recombinant (r) variants of HPg were examined that allowed dissection of the steps involved in this activation. The rate of activation of wild-type (wt) r...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Grella DK,Castellino FJ

    更新日期:1997-03-01 00:00:00

  • Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia.

    abstract::We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 x 107/kg. Seventeen patients had myeloid reconstitution and th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2420

    authors: Ooi J,Iseki T,Takahashi S,Tomonari A,Takasugi K,Shimohakamada Y,Yamada T,Ishii K,Ohno N,Nagamura F,Uchimaru K,Tojo A,Asano S

    更新日期:2004-01-15 00:00:00

  • Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas.

    abstract::LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kingma DW,Weiss WB,Jaffe ES,Kumar S,Frekko K,Raffeld M

    更新日期:1996-07-01 00:00:00

  • Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines.

    abstract::Lumiliximab is a chimeric macaque-human monoclonal antibody to CD23, a protein expressed on virtually all chronic lymphocytic leukemia (CLL) cells. We examined the ability of lumiliximab to mediate apoptosis, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity against primary CLL cells and ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-03-082024

    authors: Pathan NI,Chu P,Hariharan K,Cheney C,Molina A,Byrd J

    更新日期:2008-02-01 00:00:00

  • The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies.

    abstract::The treatment of multiple myeloma has evolved significantly over the last decades from primarily alkylator-based chemotherapeutic agents with minimal efficacy to the introduction of more effective agents including immune modulators and proteasome inhibitors, which have changed the landscape of therapy for this disease...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2016-05-636357

    authors: Hoyos V,Borrello I

    更新日期:2016-09-29 00:00:00

  • Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma.

    abstract::Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-02-0475

    authors: Kleinhans M,Tun-Kyi A,Gilliet M,Kadin ME,Dummer R,Burg G,Nestle FO

    更新日期:2003-02-15 00:00:00

  • In vitro maturation of nascent reticulocytes to erythrocytes.

    abstract::Most studies of mammalian reticulocyte maturation have used blood reticulocytes. Nascent reticulocytes, as found in bone marrow, have not been available in developmentally synchronized populations. Nascent murine reticulocytes formed in vitro by enucleation of Friend virus-infected erythroblasts were purified and recu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-02-0616

    authors: Koury MJ,Koury ST,Kopsombut P,Bondurant MC

    更新日期:2005-03-01 00:00:00

  • Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma.

    abstract::Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lym...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chatterjee M,Barcos M,Han T,Liu XL,Bernstein Z,Foon KA

    更新日期:1990-11-01 00:00:00

  • Neoplastic human T-cells capable of responding to multiple human alloantigens.

    abstract::Monoclonally-derived neoplastic T-cells from a patient with cutaneous T-cell lymphoma respond to multiple human HLA-D antigens in mixed lymphocyte culture. The implications of this phenomenon relevant to normal T-cell function and to malignancy are discussed. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rubenfeld MR,Edelson RL,Löfström LM,Berger CL,Warburton D

    更新日期:1980-03-01 00:00:00

  • Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency.

    abstract::Fibrillar collagens are among the most potent activators of platelets and play an important role in the initiation of thrombosis. The glycoprotein VI (GPVI)/FcRgamma-chain complex is a central collagen receptor and inhibitors of GPVI produce a major defect in arterial thrombogenesis. In this study we have examined art...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4244

    authors: Mangin P,Yap CL,Nonne C,Sturgeon SA,Goncalves I,Yuan Y,Schoenwaelder SM,Wright CE,Lanza F,Jackson SP

    更新日期:2006-06-01 00:00:00

  • Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump.

    abstract::Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indee...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-04-1398

    authors: Burger H,van Tol H,Boersma AW,Brok M,Wiemer EA,Stoter G,Nooter K

    更新日期:2004-11-01 00:00:00

  • Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia.

    abstract::To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-id...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sullivan KM,Weiden PL,Storb R,Witherspoon RP,Fefer A,Fisher L,Buckner CD,Anasetti C,Appelbaum FR,Badger C

    更新日期:1989-05-01 00:00:00

  • Germline CDKN2A mutation implicated in predisposition to multiple myeloma.

    abstract::Germline mutations of the CDKN2A (p16(INK4A)) tumor suppressor gene predispose patients to melanoma and pancreatic carcinoma. In contrast, mutations of the murine CDKN2A gene predispose BALB/c mice to pristane-induced plasmacytoma. We describe here a family in which a germline mutation of CDKN2A is present in 4 indivi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dilworth D,Liu L,Stewart AK,Berenson JR,Lassam N,Hogg D

    更新日期:2000-03-01 00:00:00

  • CD5 and immunoglobulin V gene expression in B-cell lymphomas and chronic lymphocytic leukemia.

    abstract::We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mayer R,Logtenberg T,Strauchen J,Dimitriu-Bona A,Mayer L,Mechanic S,Chiorazzi N,Borche L,Dighiero G,Mannheimer-Lory A

    更新日期:1990-04-01 00:00:00

  • Mapping of distinct von Willebrand factor domains interacting with platelet GPIb and GPIIb/IIIa and with collagen using monoclonal antibodies.

    abstract::We have used monoclonal antibodies (M Abs) and proteolytic fragmentation to localize structurally the functional sites of human von Willebrand factor (vWF) responsible for interaction with membrane glycoproteins GPIb, GPIIb/IIIa, and with collagen. SpII (215 kd) and SpIII (320 kd), the S aureus V-8 protease homodimeri...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Girma JP,Kalafatis M,Piétu G,Lavergne JM,Chopek MW,Edgington TS,Meyer D

    更新日期:1986-05-01 00:00:00

  • Efficient transduction of pigtailed macaque hematopoietic repopulating cells with HIV-based lentiviral vectors.

    abstract::Lentiviral vectors are attractive for hematopoietic stem cell (HSC) gene therapy because they do not require mitosis for nuclear entry, they efficiently transduce hematopoietic repopulating cells, and self-inactivating (SIN) designs can be produced at high titer. Experiments to evaluate HIV-derived lentiviral vectors ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-09-115022

    authors: Trobridge GD,Beard BC,Gooch C,Wohlfahrt M,Olsen P,Fletcher J,Malik P,Kiem HP

    更新日期:2008-06-15 00:00:00

  • GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome.

    abstract::Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-01-0013

    authors: Hitzler JK,Cheung J,Li Y,Scherer SW,Zipursky A

    更新日期:2003-06-01 00:00:00

  • HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration.

    abstract::HGAL is a newly identified germinal center (GC)-specific gene whose expression by the tumor cells correlates with a favorable prognosis in patients with diffuse large B-cell and classical Hodgkin lymphomas. The function of HGAL is unknown. Previous studies demonstrated that HGAL is dispensable for GC formation, immuno...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-04-087775

    authors: Lu X,Chen J,Malumbres R,Cubedo Gil E,Helfman DM,Lossos IS

    更新日期:2007-12-15 00:00:00

  • HIV-1 Nef drives macrophages into hiding.

    abstract::In this issue of Blood, Vérollet et al show that expression of the HIV-1–derived protein Nef alters the migratory mode adopted by macrophages, enhancing macrophage tissue infiltration and explaining the observed accumulation of tissue-resident macrophages in some HIV-infected patients. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2015-01-618983

    authors: Morley SC

    更新日期:2015-03-05 00:00:00

  • Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs.

    abstract::Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene on the X-chromosome that result in skeletal and cardiac muscle damage and premature death. Studies in mice, including the mdx mouse model of DMD, have demonstrated that circulating bone marrow-derived cells can participate in skeletal musc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-06-2247

    authors: Dell'Agnola C,Wang Z,Storb R,Tapscott SJ,Kuhr CS,Hauschka SD,Lee RS,Sale GE,Zellmer E,Gisburne S,Bogan J,Kornegay JN,Cooper BJ,Gooley TA,Little MT

    更新日期:2004-12-15 00:00:00

  • Structural and functional characterization of a specific antidote for ticagrelor.

    abstract::Ticagrelor is a direct-acting reversibly binding P2Y12 antagonist and is widely used as an antiplatelet therapy for the prevention of cardiovascular events in acute coronary syndrome patients. However, antiplatelet therapy can be associated with an increased risk of bleeding. Here, we present data on the identificatio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-01-622928

    authors: Buchanan A,Newton P,Pehrsson S,Inghardt T,Antonsson T,Svensson P,Sjögren T,Öster L,Janefeldt A,Sandinge AS,Keyes F,Austin M,Spooner J,Gennemark P,Penney M,Howells G,Vaughan T,Nylander S

    更新日期:2015-05-28 00:00:00

  • Notch-dependent control of myelopoiesis is regulated by fucosylation.

    abstract::Cell-cell contact-dependent mechanisms that modulate proliferation and/or differentiation in the context of hematopoiesis include mechanisms characteristic of the interactions between members of the Notch family of signal transduction molecules and their ligands. Whereas Notch family members and their ligands clearly ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-11-115204

    authors: Zhou L,Li LW,Yan Q,Petryniak B,Man Y,Su C,Shim J,Chervin S,Lowe JB

    更新日期:2008-07-15 00:00:00

  • A markedly disrupted skeletal network with abnormally distributed intramembrane particles in complete protein 4.1-deficient red blood cells (allele 4.1 Madrid): implications regarding a critical role of protein 4.1 in maintenance of the integrity of the r

    abstract::Electron microscopic (EM) studies were performed to clarify the interactions of membrane proteins in the red blood cell membrane structure in situ of a homozygous patient with total deficiency of protein 4.1 who carried a point mutation of the downstream translation initiation codon (AUG --> AGG) of the protein 4.1 ge...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yawata A,Kanzaki A,Gilsanz F,Delaunay J,Yawata Y

    更新日期:1997-09-15 00:00:00

  • Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishin

    abstract::The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients und...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.3.806

    authors: Drobyski WR,Klein J,Flomenberg N,Pietryga D,Vesole DH,Margolis DA,Keever-Taylor CA

    更新日期:2002-02-01 00:00:00