当前位置： SCI文献检索 > BRITISH JOURNAL OF HAEMATOLOGY期刊下所有文献 > High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate.

High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate.

Abstract：

:CD19 and CD21 (CR2) are co-receptors found on B-cells and various B-cell lymphomas, including non-Hodgkin lymphoma. To evaluate their suitability as targets for therapy of such lymphomas using internalization-dependent antibody-drug conjugates [such as antibody-4-(N-maleimidomethyl)cyclohexane-1-carboxylate, (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine) (MCC-DM1) conjugates, which require lysosomal degradation of the antibody moiety for efficacy], we examined uptake of antibodies to CD19 and CD21 in a panel of B-cell lines. Anti-CD21 antibodies were not sufficiently internalized even in the highest CD21-expressing Raji cells, resulting in lack of efficacy with anti-CD21-MCC-DM1 conjugates. Anti-CD19 antibody uptake was variable, and was unexpectedly negatively correlated with CD21 expression. Thus, high CD21-expressing Raji, ARH77 and primary B-cells only very slowly internalized anti-CD19 antibodies, while CD21-negative or low expressing cells, including Ramos and Daudi, rapidly internalized these antibodies in clathrin-coated vesicles followed by lysosomal delivery. Anti-CD19-MCC-DM1 caused greater cytotoxicity in the faster anti-CD19-internalizing cell lines, implying that the rate of lysosomal delivery and subsequent drug release is important. Furthermore, transfection of Ramos cells with CD21 impeded anti-CD19 uptake and decreased anti-CD19-MCC-DM1 efficacy, suggesting that CD21-negative tumours should respond better to such anti-CD19 conjugates. This may have possible clinical implications, as anti-CD21 immunohistochemistry revealed only approximately 30% of 54 diffuse large B-cell lymphoma patients lack CD21 expression.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Ingle GS,Chan P,Elliott JM,Chang WS,Koeppen H,Stephan JP,Scales SJ

doi

10.1111/j.1365-2141.2007.06883.x

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

46-58

issue

1

eissn

0007-1048

issn

1365-2141

pii

BJH6883

journal_volume

140

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF HAEMATOLOGY文献大全
  • Progress in central nervous system lymphomas.

    abstract：:Until recently, primary central nervous system lymphoma (PCNSL) was associated with a uniformly dismal prognosis. It is now reasonable to anticipate long-term survival and possibly cure for a significant proportion of patients diagnosed with PCNSL. Accumulated data generated over the past 10 years has provided evidenc...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.12938

    authors： Wang CC,Carnevale J,Rubenstein JL

    更新日期：2014-08-01 00:00:00

  • How we manage patients with hereditary haemochromatosis.

    abstract：:A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In gene...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.14376

    authors： Rombout-Sestrienkova E,van Kraaij MG,Koek GH

    更新日期：2016-12-01 00:00:00

  • Polycythaemia-inducing mutations in the erythropoietin receptor (EPOR): mechanism and function as elucidated by epidermal growth factor receptor-EPOR chimeras.

    abstract：:Primary familial and congenital polycythaemia (PFCP) is a disease characterized by increased red blood cell mass, and can be associated with mutations in the intracellular region of the erythropoietin (EPO) receptor (EPOR). Here we explore the mechanisms by which EPOR mutations induce PFCP, using an experimental syste...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.12782

    authors： Gross M,Ben-Califa N,McMullin MF,Percy MJ,Bento C,Cario H,Minkov M,Neumann D

    更新日期：2014-05-01 00:00:00

  • Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis.

    abstract：:Myeloproliferative disorders (MPD) are reported in 25-65% of patients with splanchnic vein thrombosis (SVT). Diagnostic criteria for MPD have not been fully established in this context. Using clusters of abnormal megakaryocytes in bone marrow (BM) biopsy as a reference standard for Philadelphia negative MPD, we assess...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2005.05490.x

    authors： Chait Y,Condat B,Cazals-Hatem D,Rufat P,Atmani S,Chaoui D,Guilmin F,Kiladjian JJ,Plessier A,Denninger MH,Casadevall N,Valla D,Brière JB

    更新日期：2005-05-01 00:00:00

  • Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up.

    abstract：:35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1998.01078.x

    authors： Butler AC,Tait RC

    更新日期：1998-12-01 00:00:00

  • Reduced intensity allogeneic stem cell transplantation for younger patients with myelofibrosis.

    abstract：:Allogeneic stem cell transplantation (alloSCT) is a curative procedure for myelofibrosis. Elderly people are mainly affected, limiting the feasibility of myeloablative regimens. The introduction of reduced-intensity conditioning (RIC) made alloSCT feasible for older patients. Nevertheless, the incidence of myelofibros...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.15952

    authors： Mannina D,Zabelina T,Wolschke C,Heinzelmann M,Triviai I,Christopeit M,Badbaran A,Bonmann S,von Pein UM,Janson D,Ayuk F,Kröger N

    更新日期：2019-08-01 00:00:00

  • Association of autoantibodies against platelet glycoproteins Ib/IX and IIb/IIIa, and platelet-reactive anti-HIV antibodies in thrombocytopenic narcotic addicts.

    abstract：:The levels of platelet-associated Igs (PAIgs) and plasma circulating antiplatelet antibodies were evaluated by a flow cytometric immunofluorescence assay (FCIFA), an enzyme-linked immunoassay (ELISA), and a platelet radioactive antiglobulin test (PRAT), in a group of 45 human immunodeficiency virus (HIV)-infected intr...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1996.00502.x

    authors： Gonzalez-Conejero R,Rivera J,Rosillo MC,Cano A,Rodriguez T,Vicente V

    更新日期：1996-05-01 00:00:00

  • Autologous stem cell transplantation: evaluation of erythropoietic reconstitution by highly fluorescent reticulocyte counts, erythropoietin, soluble transferrin receptors, ferritin, TIBC and iron dosages.

    abstract：:The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autol...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1997.d01-2104.x

    authors： Testa U,Rutella S,Martucci R,Scambia G,D'Onofrio G,Pierelli L,Sica S,Benedetti Panici PL,Menichella G,Foti E,Mastroberardino G,Mancuso S,Leone G,Peschle C

    更新日期：1997-03-01 00:00:00

  • Demonstration of three distinct immunological disorders on erythropoiesis in a patient with pure red cell aplasia and autoimmune haemolytic anaemia associated with thymoma.

    abstract：:A patient with pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA), associated with a thymoma which had already been removed, was studied in order to investigate the pathogenesis of PRCA and AIHA. The autoantibody eluted from the surface of the patient's red blood cells (RBC) reacted with the large E...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1988.tb04239.x

    authors： Taniguchi S,Shibuya T,Morioka E,Okamura T,Okamura S,Inaba S,Niho Y

    更新日期：1988-04-01 00:00:00

  • Ernest Beutler: his life and contribution to medical science.

    abstract：:Ernest Beutler was one of the preeminent haematologists of the last half of the 20th and the early 21st century. In a career that spanned six decades, his research interests included such diverse areas as red cell metabolism, blood preservation, glycolipid storage diseases, leukaemias and iron metabolism. Indeed, he w...

    journal_title：British journal of haematology

    pub_type： 传,历史文章,杂志文章

    doi：10.1111/j.1365-2141.2010.08542.x

    authors： Beutler S,Beutler B

    更新日期：2011-03-01 00:00:00

  • Transient familial haemophagocytic lymphohistiocytosis reactivation post-CD34 haematopoietic stem cell transplantation.

    abstract：:Familial haemophagocytic lymphohistiocytosis (FHLH) is a genetic disorder caused by defective lymphocyte cytotoxicity, resulting in impaired lymphocyte homeostasis and macrophage infiltration of solid tissues and bone marrow, with extensive haemophagocytosis. It is invariably fatal unless treated by allogeneic haemato...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2005.05615.x

    authors： Almousa H,Ouachée-Chardin M,Picard C,Radford-Weiss I,Caillat-Zucman S,Cavazzana-Calvo M,Blanche S,de Saint Basile G,Le Deist F,Fischer A

    更新日期：2005-08-01 00:00:00

  • Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications.

    abstract：:The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers w...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.1996.4651006.x

    authors： García-Sanz R,González M,Orfão A,Moro MJ,Hernández JM,Borrego D,Carnero M,Casanova F,Bárez A,Jiménez R,Portero JA,San Miguel JF

    更新日期：1996-04-01 00:00:00

  • Leucocyte alkaline phosphatase identifies terminally differentiated normal neutrophils and its lack in chronic myelogenous leukaemia is not dependent on p210 tyrosine kinase activity.

    abstract：:Leucocyte alkaline phosphatase (LAP) is a marker of post-mitotic granulocytes and its activity is reduced or absent in chronic myelogenous leukaemia (CML) granulocytes as a consequence of LAP messenger RNA (mRNA) deficiency. We provide evidence that along the granulocytic maturation in normal marrow, the acquisition o...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：

    authors： Dotti G,Garattini E,Borleri G,Masuhara K,Spinelli O,Barbui T,Rambaldi A

    更新日期：1999-04-01 00:00:00

  • Thymidine kinase isoenzymes in chronic lymphocytic leukaemia.

    abstract：:The profile of thymidine kinase isoenzymes was determined in peripheral blood lymphocytes from 14 patients with chronic lymphocytic leukaemia (CLL) and 31 controls. Twelve patients with indolent disease showed TK2 isoenzyme activity, while two patients in whom the disease evolved and two patients who presented with ag...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1981.tb07251.x

    authors： Ellims PH,Gan TE,Van der Weyden MB

    更新日期：1981-11-01 00:00:00

  • Fluctuating deformability of oxygenated sickle erythrocytes in the asymptomatic state and in painful crisis.

    abstract：:A new gravity filtration technique for the study of sickle cell deformability has shown a significant loss of filterability of oxygenated erythrocytes on day 2 of painful crisis in eight patients with homozygous sickle cell anaemia; there was no increase in irreversibly sickled cell (ISC) count. Serial study (mean of ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1985.tb03001.x

    authors： Lucas GS,Caldwell NM,Stuart J

    更新日期：1985-02-01 00:00:00

  • Immunochemical characterization of an autoantigen on platelet glycoprotein IIb in chronic ITP: comparison with the Baka alloantigen.

    abstract：:Employing an immunoblotting procedure, we have identified and characterized an autoantigen carried on glycoprotein (GP) IIb in a patient with chronic idiopathic thrombocytopenic purpura (ITP), and have compared the location of the autoantigen with that of the platelet-specific alloantigen Baka. Immunoblots, using the ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1989.tb06278.x

    authors： Tomiyama Y,Kurata Y,Shibata Y,Honda S,Furubayashi T,Mizutani H,Tsubakio T,Yonezawa T,Tarui S

    更新日期：1989-01-01 00:00:00

  • Interleukin 2 enhances cytotoxic cell function in vitro after T-cell depleted marrow transplantation.

    abstract：:After T-cell depleted marrow transplantation, there is a rapid recovery of cytotoxic effector cells, with activity against targets not susceptible to killing by 'resting' natural killer cells. These targets include Epstein-Barr virus transformed B cells and leukaemic cell lines. Activated killer cell function declines...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1987.tb02347.x

    authors： Leger O,Drexler HG,Reittie JE,Secker-Walker L,Prentice HG,Brenner MK

    更新日期：1987-11-01 00:00:00

  • Selective in vitro expansion and efficient retroviral transduction of human CD34+ CD38- haematopoietic stem cells.

    abstract：:Ex vivo expansion of primitive human haematopoietic stem cells (HSC) is clinically relevant for stem cell transplantation and gene therapy. Here, we demonstrate the selective expansion of CD34+CD38- cells from purified CD34+ cells upon stimulation with Flt3-ligand, stem cell factor and thrombopoietin. Over a 100-fold ...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1046/j.1365-2141.2002.03370.x

    authors： Ng YY,Bloem AC,van Kessel B,Lokhorst H,Logtenberg T,Staal FJ

    更新日期：2002-04-01 00:00:00

  • The issue of consent in medical practice.

    abstract：:Following a recent court judgment, legal and moral issues surrounding consent have been thrown into the spotlight. Elizabeth Larner, Solicitor, and Rachel Carter, Partner, of Wollen Michelmore LLP, look at the issues surrounding consent, including where problems arise in the fields of clinical negligence and non-accid...

    journal_title：British journal of haematology

    pub_type： 杂志文章,评审

    doi：10.1111/bjh.13795

    authors： Larner E,Carter R

    更新日期：2016-01-01 00:00:00

  • Progenitor genotyping reveals a complex clonal architecture in a subset of CALR-mutated myeloproliferative neoplasms.

    abstract：:The identification of acquired CALR mutations in patients with essential thrombocythaemia (ET) or myelofibrosis (MF) has meant that disease-initiating mutations can now be detected in about 90% of all patients with a myeloproliferative neoplasm (MPN). Here, we show that only those CALR mutations that cause a +1 frames...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.14512

    authors： Martin S,Wright CM,Scott LM

    更新日期：2017-04-01 00:00:00

  • Cellular levels of mRNA from c-myc, c-myb and c-fes onc-genes in normal myeloid and erythroid precursors of human bone marrow: an in situ hybridization study.

    abstract：:The expression of three onc-genes, c-myc, c-myb and c-fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by "in situ" hybridization with tritium-labelled probes. A relatively large amount of m-RNA from the three onc-genes was detected in myeloblasts and promy...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1986.tb02931.x

    authors： Emilia G,Donelli A,Ferrari S,Torelli U,Selleri L,Zucchini P,Moretti L,Venturelli D,Ceccherelli G,Torelli G

    更新日期：1986-02-01 00:00:00

  • A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

    abstract：:Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 )...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/bjh.17128

    authors： Vogel DJ,Formenti F,Retter AJ,Vasques F,Camporota L

    更新日期：2020-11-01 00:00:00

  • Type I von Willebrand disease, subtype 'platelet low': decreased platelet adhesion can be explained by low synthesis of von Willebrand factor in endothelial cells.

    abstract：:Endothelial cells (EC) were isolated from the umbilical vein of a newborn girl with type I 'platelet low' von Willebrand disease (I vWD) and endothelial localization and release and the ability of subendothelial von Willebrand factor (vWF) to support platelet adhesion were compared with those of normal EC. vWF was det...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1993.tb04636.x

    authors： Federici AB,de Groot PG,Moia M,Ijsseldijk MJ,Sixma JJ,Mannucci PM

    更新日期：1993-01-01 00:00:00

  • Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals.

    abstract：:The French-American-British (FAB) classification assigns patients with myelodysplastic syndromes to the category of refractory anaemia with excess blasts (RAEB) if they have a medullary blast count of 5-20%, and/or a peripheral blast count of 2-5%. The new World Health Organization (WHO) classification subdivides RAEB...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2005.05853.x

    authors： Germing U,Strupp C,Kuendgen A,Aivado M,Giagounidis A,Hildebrandt B,Aul C,Haas R,Gattermann N

    更新日期：2006-01-01 00:00:00

  • Stimulation of human haemopoietic cells by colony stimulating factors: adherent cell dependent colony stimulating activity in human serum.

    abstract：:The number of granulocyte-macrophage clones formed in agar culture of bone marrow is dependent on levels of colony stimulating activity (CSA) a proposed in vivo haemopoietic regulator. A dose-response relationship for stimulation of human haemopoietic cells by CSA is demonstrated, which could be explained by threshold...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1977.tb00626.x

    authors： Francis GE,Berney JJ,Hoffebrand AV

    更新日期：1977-04-01 00:00:00

  • Bone marrow biopsy in myelodysplastic syndromes: morphological characteristics and contribution to the study of prognostic factors.

    abstract：:Ten characteristics of bone marrow (BM) biopsies in paraffin sections, obtained at diagnosis from patients with myelodysplastic syndromes (MDS) classified according to the FAB criteria, were analysed to identify both the most relevant morphologic data and any possible influence on survival. Agreement between two obser...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1990.tb02612.x

    authors： Ríos A,Cañizo MC,Sanz MA,Vallespí T,Sanz G,Torrabadella M,Gomis F,Ruiz C,San Miguel JF

    更新日期：1990-05-01 00:00:00

  • Functional regulation of D-type cyclins by insulin-like growth factor-I and serum in multiple myeloma cells.

    abstract：:D-type cyclin genes are universally dysregulated in multiple myeloma (MM), but the functional consequences are unclear as D-type cyclin gene expression does not correlate with proliferation or disease progression. We examined the protein expression and regulation of D-type cyclins and other cell cycle regulators in hu...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2007.06789.x

    authors： Glassford J,Rabin N,Lam EW,Yong KL

    更新日期：2007-10-01 00:00:00

  • Integrated DNA copy number and methylation profiling of lymphoid neoplasms using a single array.

    abstract：:Changes in DNA copy number (CN) and DNA methylation represent important aberrations for lymphomas and other cancers. Here, for the first time, we show that the Illumina Infinium Methylation (IIM) assay, although not originally designed for CN profiling, is able to estimate CN changes. We compared the IIM CN profiles t...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.2011.08946.x

    authors： Kwee I,Rinaldi A,Rancoita P,Rossi D,Capello D,Forconi F,Giuliani N,Piva R,Inghirami G,Gaidano G,Zucca E,Bertoni F

    更新日期：2012-02-01 00:00:00

  • The generation of thrombin in vivo induces the selective loss of high molecular weight multimers of von Willebrand factor and the reversible sequestration of platelets.

    abstract：:Various levels of thrombin generation were induced by the infusion of a combination of factor Xa (F.Xa) and phosphatidylcholine/phosphatidylserine (PCPS) vesicles into normal dogs and non-human primates. In the dog, an immediate loss of von Willebrand factor antigen (vWF:Ag) with a progressive recovery to normal level...

    journal_title：British journal of haematology

    pub_type： 杂志文章

    doi：10.1111/j.1365-2141.1993.tb03219.x

    authors： Toh CH,Hoogendoorn H,Giles AR

    更新日期：1993-12-01 00:00:00

  • Analysis of very elderly (≥80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome.

    abstract：:Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily ...

    journal_title：British journal of haematology

    pub_type： 杂志文章,多中心研究

    doi：10.1111/j.1365-2141.2011.08934.x

    authors： Nabhan C,Smith SM,Helenowski I,Ramsdale E,Parsons B,Karmali R,Feliciano J,Hanson B,Smith S,McKoy J,Larsen A,Hantel A,Gregory S,Evens AM

    更新日期：2012-01-01 00:00:00