Abstract：
:The costimulatory effects of CD27 on T lymphocyte effector function and memory formation has been confined to evaluations in mouse models, in vitro human cell culture systems, and clinical observations. Here, we tested whether CD27 costimulation actively enhances human T-cell function, expansion, and survival in vitro and in vivo. Human T cells transduced to express an antigen-specific chimeric antigen receptor (CAR-T) containing an intracellular CD3 zeta (CD3ζ) chain signaling module with the CD27 costimulatory motif in tandem exerted increased antigen-stimulated effector functions in vitro, including cytokine secretion and cytotoxicity, compared with CAR-T with CD3ζ alone. After antigen stimulation in vitro, CD27-bearing CAR-T cells also proliferated, up-regulated Bcl-X(L) protein expression, resisted apoptosis, and underwent increased numerical expansion. The greatest impact of CD27 was noted in vivo, where transferred CAR-T cells with CD27 demonstrated heightened persistence after infusion, facilitating improved regression of human cancer in a xenogeneic allograft model. This tumor regression was similar to that achieved with CD28- or 4-1BB-costimulated CARs, and heightened persistence was similar to 4-1BB but greater than CD28. Thus, CD27 costimulation enhances expansion, effector function, and survival of human CAR-T cells in vitro and augments human T-cell persistence and antitumor activity in vivo.
journal_name
Bloodjournal_title
Bloodauthors
Song DG,Ye Q,Poussin M,Harms GM,Figini M,Powell DJ Jrdoi
10.1182/blood-2011-03-344275subject
Has Abstractpub_date
2012-01-19 00:00:00pages
696-706issue
3eissn
0006-4971issn
1528-0020pii
blood-2011-03-344275journal_volume
119pub_type
杂志文章相关文献
BLOOD文献大全abstract：:Mice carrying a conditional prothrombin knockout allele (fII(lox)) were established to develop an experimental setting for exploring the importance of thrombin in the maintenance of vascular integrity, the inflammatory response, and disease processes in adult animals. In the absence of Cre-mediated recombination, homo...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-07-169003
更新日期：2009-01-15 00:00:00
abstract：:A key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function-associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2009-05-224428
更新日期：2010-09-16 00:00:00
abstract：:Circulating IgG autoantibodies that produce cytoplasmic immunofluorescence staining of ethanol-fixed normal neutrophils have recently been found in a large percentage of patients with active Wegener's granulomatosis. Such autoantibodies are rarely found in other diseases and are therefore virtually diagnostic of Wegen...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Cytogenetic and histopathologic data were correlated with clinical parameters from 423 patients with non-Hodgkin's lymphoma (NHL). Clinical correlations were performed on subgroups of 149 patients with low-grade lymphoma (LG) and 205 patients with diffuse lymphoma with a large cell component (DLLC). Correlations were ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:Marrow cells of myeloid lineage from 115 patients with myelodysplastic syndrome (MDS) were characterized by multidimensional flow cytometry and compared with findings in 104 patients with various disorders and 25 healthy donors. Based on phenotypic and scatter characteristics, a flow cytometric scoring system (FCSS) w...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2002-09-2768
更新日期：2003-07-01 00:00:00
abstract：:Escape from immune detection favors both tumor survival and progression, and new approaches to circumvent this are essential to combat cancers. Nonvirulent, tumor-tropic bacteria, such as Salmonella typhimurium, can unmask a tumor by transforming it into a site of inflammation; however, the nonspecific invasiveness of...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-12-474098
更新日期：2013-08-01 00:00:00
abstract：:Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferatio...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Graft-versus-host disease (GVHD) is the main complication of allogeneic stem cell transplantation. However, diagnosis of GVHD and evaluation of response to immunosuppressive treatment is sometimes difficult. Since apoptosis is the histopathologic hallmark in GVHD, we investigated whether active GVHD-induced target org...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-10-049817
更新日期：2007-12-15 00:00:00
abstract：:Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children wi...
journal_title：Blood
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：2000-03-01 00:00:00
abstract：:We compared the ability of aspirin to suppress platelet aggregation and thromboxane synthesis in ten normal subjects and ten patients with diabetic angiopathy and high rate of entry of new platelets into the circulation. When single doses of 100 to 1,000 mg aspirin were ingested daily for 1 month, there were time gaps...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Congenital afibrinogenemia is a rare inherited coagulopathy, characterized by very low or unmeasurable plasma levels of immunoreactive fibrinogen. So far, 25 mutations have been identified in afibrinogenemia, 17 in the Aalpha, 6 in the gamma, and only 2 in the Bbeta fibrinogen-chain genes. Here, 2 afibrinogenemic prob...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2002-06-1647
更新日期：2002-12-15 00:00:00
abstract：:MicroRNAs (miRNAs) have emerged as important regulators of the immune system. However, despite this prominence, our understanding of the function of miRNAs in the early hematopoietic stages is incomplete. In this study, we found that miR-139-5p negatively regulated the proliferation of hematopoietic stem cells and pro...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2016-02-702464
更新日期：2016-10-27 00:00:00
abstract：:Kaposi sarcoma-associated herpesvirus (KSHV)-related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus-driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most acc...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.v98.12.3473
更新日期：2001-12-01 00:00:00
abstract：:We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyt...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Allogeneic stem cell transplantation (SCT) is now a commonplace procedure. Clinicians who care for patients with hematologic malignancies and aplastic anemia are almost certain to follow up patients after SCT. This review is intended to help clinicians observe patients for probably the most important late complication...
journal_title：Blood
pub_type： 杂志文章,评审
doi：10.1182/blood.v97.5.1196
更新日期：2001-03-01 00:00:00
abstract：:Functional studies on native human dendritic cells (DCs) are hampered by technical difficulties in preparing fresh DCs. Recently, with the help of the monoclonal antibody M-DC8, we succeeded in isolating a major subpopulation of human blood DCs by a one-step immunomagnetic separation procedure. These cells strongly ex...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2002-08-15 00:00:00
abstract：:To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1977-03-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic va...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-11-011650
更新日期：2006-09-15 00:00:00
abstract：:Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Somatic mutation in immunoglobulin variable (V) region genes occurs largely in the germinal center and, after neoplastic transformation, imprints V genes of B-cell tumors with the mutational history of the cell of origin. Recently, it has been found that chronic lymphocytic leukemia (CLL) consists of 2 subsets, each w...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Leukocyte rolling precedes firm adhesion and emigration in inflammatory cell recruitment. Both P-selectin, an endothelial lectin that binds to sialylated O-glycans containing sialyl-Lewisx (sLex) on the granulocyte surface, and leukocyte L-selectin have been shown to mediate leukocyte rolling in vivo. Here, we investi...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1995-06-15 00:00:00
abstract：:The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1996-02-15 00:00:00
abstract：:Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluor...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1998-07-15 00:00:00
abstract：:The common γ chain (CD132) is a subunit of the interleukin (IL) receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Because levels of several of these cytokines were shown to be increased in the serum of patients developing acute and chronic graft-versus-host disease (GVHD), we reasoned that inhibition of CD132 co...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2014-06-581793
更新日期：2015-01-15 00:00:00
abstract：:Umbilical cord blood (UCB) is used for HSCT. It is known that UCB can comprise Ag-specific T cells. Here we question whether solely transmaternal cell flow may immunize UCB. Twenty-three female UCB samples were collected from healthy mothers and analyzed for minor histocompatibility Ag HY-specific responses. Forty-two...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-02-410571
更新日期：2012-07-19 00:00:00
abstract：:TLRs expressed on dendritic cells (DCs) differentially activate DCs when activated alone or in combination, inducing distinct cytokines and costimulatory molecules that influence T-cell responses. Defining the requirements of DCs to program T cells during priming to become memory rather than effector cells could enhan...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-11-317966
更新日期：2011-06-16 00:00:00
abstract：:Analysis of fresh human tumors have indicated that patients with B type lymphoproliferative diseases and the majority of patients with acute lymphoblastic leukemia (ALL) express elevated levels of p53 production. It is suggested that in these human malignancies, p53 may provide a novel tool for monitoring cancer activ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Normal human bone marrow contains cells capable of forming colonies of hemopoietic cells in fibrin clots in diffusion chambers implanted intraperitoneally (i.p.) into irradiated mice. The present paper describes the proliferation of such colony-forming units (CFUD) in cultures in vivo. Cells harvested from diffusion c...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1977-03-01 00:00:00
abstract：:Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1993-09-15 00:00:00
abstract：:Using Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) as a model, our aim has been to develop a molecular cytogenetic method of high resolution analysis for monitoring the frequency of cells with nonrandom chromosome rearrangements in the bone marrow of patients receiving treatment for hemato...
journal_title：Blood
pub_type： 临床试验,杂志文章
doi：
更新日期：1995-09-15 00:00:00
