Abstract:
:Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Mihara K,Yanagihara K,Takigahira M,Kitanaka A,Imai C,Bhattacharyya J,Kubo T,Takei Y,Yasunaga S,Takihara Y,Kimura Adoi
10.1111/j.1365-2141.2010.08297.xsubject
Has Abstractpub_date
2010-10-01 00:00:00pages
37-46issue
1eissn
0007-1048issn
1365-2141pii
BJH8297journal_volume
151pub_type
杂志文章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
更新日期:2012-01-01 00:00:00
abstract::We retrospectively report data on 28 patients with haematological malignancy and trisomy 13 (25 cases) or tetrasomy 13 (three cases) as the primary acquired cytogenetic change. Peripheral blood and/or bone marrow morphology was reviewed in 25/28 cases and the final diagnosis was as follows: AML M0 (11), AML M1 (6), AM...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.00760.x
更新日期:1998-06-01 00:00:00
abstract::To examine any role of macrophage colony-stimulating factor (M-CSF), in the immune responses in Kawasaki disease (KD), we serially assayed M-CSF and several related cytokines using ELISA. In 10 paediatric patients with KD the level of M-CSF was significantly higher in the acute phase than in the convalescent phase (14...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1999.01381.x
更新日期:1999-06-01 00:00:00
abstract::To explore the possible role of a residual or variant alphaIIbbeta3 integrin (alphaIIbbeta3) in thrombogenesis, we used a new ex vivo perfusion chamber model to examine blood from patients with different subtypes of Glanzmann's thrombasthenia (GT). Non-anticoagulated blood was perfused through capillaries coated with ...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03966.x
更新日期:2002-12-01 00:00:00
abstract::Elevated levels of haemoglobin F (Hb F) have been foudn in a wide range of haematological malignancies, but very high levels were found only in juvenile chronic myeloid leukaemia (JCML), and erythroleukaemia occurring in infancy. In both these disorders a reversion to a fetal form of erythropoiesis may occur, as judge...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00952.x
更新日期:1976-04-01 00:00:00
abstract::Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on m...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05778.x
更新日期:2005-11-01 00:00:00
abstract::In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal sc...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.12590
更新日期:2013-12-01 00:00:00
abstract::The prognostic significance of SOCS3 protein expression was determined in de novo follicular lymphomas (FL) with t(14;18) and bcl-2 overexpression. Presentation lymph nodes from 82 FL patients for whom clinical information was available were immunohistochemically segregated into SOCS3-positive (n = 42) or -negative (n...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2006.06248.x
更新日期:2006-10-01 00:00:00
abstract::We report a case of persistent infection with human parvovirus B19 (PVB19), manifesting clinically as recurrent agranulocytosis and in bone marrow biopsy as recurrent pure granulocytic aplasia. Persistence of parvovirus infection was documented by the presence of PVB19 DNA and anti-PVB19-IgM antibodies in the serum fo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1992.tb08894.x
更新日期:1992-02-01 00:00:00
abstract::Dyskeratosis congenita (DC) is an inherited disorder characterized by skin pigmentation, nail dystrophy and mucosal leucoplakia. In 1995 a Dyskeratosis Congenita Registry was established at the Hammersmith Hospital. In the 46 families recruited, 76/83 patients were male, suggesting that the major form of DC is X-linke...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1998.01103.x
更新日期:1998-12-01 00:00:00
abstract::A 29-year-old man in remission from acute myeloblastic leukaemia was treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from his HLA identical brother. Engraftment was documented on D12. Transient acute GVHD (grade II) appeared from D34. No infection complicated the BMT. Nevertheless sever...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1985.tb07359.x
更新日期:1985-04-01 00:00:00
abstract::Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tu...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1993.tb03138.x
更新日期:1993-08-01 00:00:00
abstract::It has been suggested that the iron storage protein ferritin has a number of physiological functions not directly related to iron metabolism and a number of these relate to lymphocyte and macrophage activity. The present study demonstrates a selective distribution of ferritin on lymphocyte and macrophage surface membr...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::Defects in glycoprotein (GP)IIb-IIIa or in its activation may cause abnormal platelet aggregation and a bleeding diathesis. We report studies in a 67-year-old man with a myeloproliferative disease and markedly abnormal platelet responses. By flow cytometry, platelet binding of two complex-specific anti-GPIIb-IIIa mono...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract::Cord blood (CB) has successfully been used as a stem cell source for haemopoietic reconstitution. However, a significant delay in platelet engraftment is consistently found in CB versus adult peripheral blood (PB) or bone marrow transplants. We sought to determine whether or not CB megakaryocytes have reached terminal...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2001.02954.x
更新日期:2001-08-01 00:00:00
abstract::In advanced chronic myeloid leukaemia patients, STI-571 produces complete haematological response in most cases and cytogenetic response in up to 50%. However, these patients often suffer periods of pancytopenia, which can lead to life-threatening complications, and is probably due to the small number of residual norm...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03542.x
更新日期:2002-07-01 00:00:00
abstract::Follicular lymphoma (FL) constitutes a significant proportion of lymphomas and shows frequent relapses. Beyond conventional chemotherapy, new therapeutic approaches have emerged, focussing on the interplay between lymphoma cells and the microenvironment. Here we report the immunophenotypic investigation of the microen...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.16414
更新日期:2020-05-01 00:00:00
abstract::To determine whether human red cells contain a proteolytic system capable of rapidly degrading unstable proteins, the fate of pulse-labelled puromycyl polypeptides was investigated. In erythroid bone marrow cells these unstable polypeptides were degraded to TCA-soluble fragments with a mean half-life of 4 . 5 min. How...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1983.tb02042.x
更新日期:1983-03-01 00:00:00
abstract::Sézary syndrome and Mycosis fungoides are the most common forms of cutaneous T-cell lymphomas. To assess the response to different therapies especially in Sézary syndrome, it is helpful to monitor the percentage of circulating tumour cells in the blood. The use of T-cell receptor (TCR)-Vbeta specific monoclonal antibo...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2002.03726.x
更新日期:2002-09-01 00:00:00
abstract::Flow cytometry was used to determine the percentage and number of circulating CD34+ cells in fetal blood from 100 pregnancies at 13-38 weeks gestation. When expressed as a percentage of the total number of lymphocytes, the proportion of CD34+ cells decreased exponentially from a mean of 11.1% (9.2 x 10(7)/l) at 13 wee...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1994.tb08328.x
更新日期:1994-07-01 00:00:00
abstract::We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subs...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1365-2141.1998.00825.x
更新日期:1998-08-01 00:00:00
abstract::Diamond-Blackfan anaemia (DBA) is a rare bone marrow failure syndrome characterised by anaemia, congenital anomalies and cancer predisposition. Although infections are the second leading cause of mortality in non-transplanted patients, immune function is largely unexplored. We identified quantitative deficits in serum...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章
doi:10.1111/bjh.15915
更新日期:2019-07-01 00:00:00
abstract::We used minisatellite probes to analyse by DNA fingerprints the long-term engraftment (median 4.3 years, range 1-2) of 21 bone marrow transplantation recipients for severe aplastic anaemia. Patients received their graft from histocompatible siblings. They were conditioned with cyclophosphamide (150 mg/kg) and a 6GY th...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1989.tb06313.x
更新日期:1989-04-01 00:00:00
abstract::The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents ta...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.15210
更新日期:2018-07-01 00:00:00
abstract::The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and...
journal_title:British journal of haematology
pub_type: 杂志文章,评审
doi:10.1111/bjh.16453
更新日期:2020-05-01 00:00:00
abstract::Previous studies report conflicting results concerning the potential significance of thrombophilic genotypes in postarthroplasty venous thromboembolism (VTE). This study assessed thrombophilic genotypes, haemostatic and clinical variables as independent risk factors for VTE postarthroplasty. A total number of 569 pati...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2005.05419.x
更新日期:2005-04-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous (i.v.) and subcutaneous (s.c.) injections of heparins, and may thus contribute to the antithrombotic effect of heparins. We have recently shown that total TFPI activity, plasma free TFPI antigen, and heparin releasable TFPI were ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2141.1999.01791.x
更新日期:1999-12-01 00:00:00
abstract::Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder with a high predisposition for lymphoid malignancies. The majority of NBS patients carry a homozygous founder mutation (657del5) within the NBS1 gene. The observation of a high incidence of cancer in close relatives of NBS patients suggests...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2000.01973.x
更新日期:2000-04-01 00:00:00
abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional haematopoietin which can promote production of several blood cell lineages, though the predominant target cells are neutrophils, monocytes, and their precursors. Occasional undesirable clinical effects include eosinophilia, an increase in b...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1991.tb04448.x
更新日期:1991-07-01 00:00:00
abstract::Globin synthesis was studied in four Negro families including 10 members with Hb A-HPFH and four with Hb S-HPFH. The beta/alpha specific activity ratios in 10 of these HPFH heterozygotes were similar to those of the control group. In two patients with Hb A-HPFH, the beta/alpha ratio was slightly decreased in one (0.84...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1976.tb00939.x
更新日期:1976-03-01 00:00:00