PiggyBac-engineered T cells expressing a glypican-3-specific chimeric antigen receptor show potent activities against hepatocellular carcinoma.

Abstract:

:Glypican-3 (GPC3) is an attractive target for chimeric antigen receptor (CAR)-T cell therapy, as it is overexpressed in most hepatocellular carcinoma (HCC) tissues but shows restricted expression in healthy adult tissues. Herein, we generated GPC3-specific CAR-T cells for HCC therapy by electroporation with plasmid DNA encoding the piggyBac (PB) transposon and the hyperactive piggyBac transposase simultaneously instead of by commonly-used viral vectors. Our results demonstrated that GPC3CAR gene was efficiently integrated into the genome of T cells utilizing the PB transposon system. Upon stimulation with GPC3 antigen, GPC3CAR-T cells could be effectively activated, proliferate strongly and secrete high levels of cytokines. It also was demonstrated that GPC3CAR-T cells displayed potent cytotoxicity against GPC3-positive HCC cell lines in vitro by using real-time cell analyser (RTCA) system and the JuLI™ Stage Cell History Recorder. More importantly, in a Huh-7 xenograft mouse model, GPC3CAR-T cells significantly reduced the tumour burden companied with the secretion of high levels of IFN-γ. Moreover, T cells in mice treated with GPC3CAR-T cells could infiltrate into tumour tissues and persist as effector memory T cells (TEM). Overall, our study suggests that the use of PB system-based GPC3CAR-T cell therapy could be a promising clinical strategy for patients with HCC.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Wang P,Qin W,Liu T,Jiang D,Cui L,Liu X,Fang Y,Tang X,Jin H,Qian Q

doi

10.1016/j.imbio.2019.09.009

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

151850

issue

1

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(19)30180-9

journal_volume

225

pub_type

杂志文章
  • Molecular principles of Oct2-mediated gene activation in B cells.

    abstract::The octamer motif is a crucial regulatory element for immunoglobulin promoter and enhancer function. We have investigated the molecular mechanisms that underlie octamer-mediated gene activation in B cells. This B cell-specific transcriptional regulation is subject to a novel type of regulatory mechanism. We could demo...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1016/S0171-2985(11)80540-1

    authors: Wirth T,Pfisterer P,Annweiler A,Zwilling S,König H

    更新日期:1995-07-01 00:00:00

  • Identification of genes expressed in tumor-associated macrophages.

    abstract::Most malignant tumors contain so-called tumor-associated macrophages (TAM) as a major component of their leukocytic infiltrate. To investigate the impact of the tumor microenvironment on activation and differentiation of macrophages, we established a 3-dimensional model system by culturing human monocytes within multi...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1078/0171-2985-00246

    authors: Gottfried E,Faust S,Fritsche J,Kunz-Schughart LA,Andreesen R,Miyake K,Kreutz M

    更新日期:2003-01-01 00:00:00

  • In staphylococcus enterotoxin B (SEB)-stimulated human PBMC, the LAK activity of non-T cells might have a major role in the mechanism of glomerular endothelial cells' injury.

    abstract::In this study the SEB-activated LAK cytotoxicity was identified and characterized in human peripheral blood lymphocytes (PBMC). After 3 days of SEB stimulation, the PBMC acquired a cytotoxicity against traditional LAK targets, K-562 and Daudi, beside that human glomerular endothelial cells (HGEC) were effectively lyse...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(97)80056-3

    authors: Seprényi G,Shibata T,Onody R,Kohsaka T

    更新日期:1997-06-01 00:00:00

  • Epithelial cells modulate genes associated with NF kappa B activation in co-cultured human macrophages.

    abstract::Macrophages located in airways and the alveolar space are continually exposed to different signals from the respiratory mucosa. In this respect, epithelial cells represent an important source of cytokines and mediators modulating the state of activation and/or differentiation of mononuclear phagocytes. Many of the pro...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2011.04.009

    authors: Striz I,Brabcova E,Kolesar L,Liu XD,Brabcova I,Sekerkova A,Poole JA,Jaresova M,Slavcev A,Rennard SI

    更新日期:2011-10-01 00:00:00

  • Peripheral blood natural killer cells activation status determined by CD69 upregulation predicts implantation outcome in IVF.

    abstract:PROBLEM:NK lymphocytes play critical yet poorly defined role in implantation and during development in early pregnancy. METHODS OF STUDY:Recently, we showed that the proportion of NK that expressed CD69⁺ after incubation with K562 (CD69(stim)) cells reflected the NK population excitation potential. In the present stud...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2013.09.002

    authors: Dons'koi BV,Chernyshov VP,Sirenko VY,Strelko GV,Osypchuk DV

    更新日期:2014-03-01 00:00:00

  • Insights into the immunogenetic basis of two ganglioside-associated idiotypic networks.

    abstract::The heavy-chain variable regions (VH) from 14F7 MAb, an IgG1 antibody specific for GM3(NeuGc) ganglioside, and its anti-idiotype, the 4G9 MAb, were cloned and sequenced. Comparison with previously reported sequences showed that VH 14F7 belongs to the J558(VHI) gene family and that it is highly mutated. VH 4G9 belongs ...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2006.08.005

    authors: Rodríguez M,Roque-Navarro L,López-Requena A,Moreno E,Mateo de Acosta C,Pérez R,María Vázquez A

    更新日期:2007-01-01 00:00:00

  • Hydroxytyrosol modulates Par j 1-induced IL-10 production by PBMCs in healthy subjects.

    abstract::Several papers have demonstrated the importance of substances from natural sources which can exert powerful anti-inflammatory effects. In this respect, hydroxytyrosol, one of the major elements of the phenolic components of olive oil, has been extensively studied for its anti-inflammatory activities and safety profile...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2016.07.009

    authors: Bonura A,Vlah S,Longo A,Bulati M,Melis MR,Cibella F,Colombo P

    更新日期:2016-12-01 00:00:00

  • Structural requirements for SP-D function in vitro and in vivo: therapeutic potential of recombinant SP-D.

    abstract::Surfactant protein D has multiple functions in innate immunity in the lung. The generation of SP-D knock-out mice has revealed a central role for this protein in the control of lung inflammation. Accumulating evidence in mouse models of infection and inflammation indicates that truncated recombinant forms of surfactan...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1078/0171-2985-00159

    authors: Clark H,Reid KB

    更新日期:2002-09-01 00:00:00

  • Abnormalities of B cell activation and immunoregulation in patients with chronic inflammatory liver diseases.

    abstract::The immunoglobulin production capacities of peripheral blood lymphocytes obtained from patients with various chronic inflammatory liver diseases and from normal individuals were compared. Using a reverse hemolytic plaque assay, immunoglobulin-secreting cells (ISC) were counted immediately after isolation (immediate IS...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(88)80066-4

    authors: Sieber G,Teichmann JV,Möller B,Hopf U

    更新日期:1988-12-01 00:00:00

  • GM-CSF in the generation of dendritic cells from human blood monocyte precursors: recent advances.

    abstract::Dendritic cells (DCs) play a key role in the orchestration of the immune system by virtue of their capacity to control both immunity and tolerance induction. The functions of DCs depend on the subset as well as their location and activation state. A number of in vitro protocols, developed to recapitulate DC generation...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.imbio.2008.07.017

    authors: Conti L,Gessani S

    更新日期:2008-01-01 00:00:00

  • Induction of tolerance to non-H-2 alloantigens is not restricted by the MHC molecules expressed on the donor cells in cyclophosphamide-induced tolerance.

    abstract::A long-lasting skin tolerance to non-H-2 alloantigens has been reported to be readily induced, when the recipient mice were primed intravenously (i.v.) with 5 x 10(7) spleen cells (SC) plus 1.5 x 10(7) bone marrow cells (BMC) from the H-2 identical strains of mice, and treated intraperitoneally (i.p.) with 200 mg/kg C...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(11)80511-5

    authors: Tomita Y,Nomoto K

    更新日期:1990-11-01 00:00:00

  • Frequency of Valpha24+CD161+ natural killer T cells and invariant TCRAV24-AJ18 transcripts in atopic and non-atopic individuals.

    abstract::Th2 cells play a central role in type I allergies. However, the source of interleukin-4 which may lead to a Th1/Th2 imbalance is unknown. Valpha24+CD161+ Natural killer T (NKT) cells secrete high amounts of interleukin-4 and/or interferon-gamma and are assumed to participate in the initiation of Th1/Th2 immune respons...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1078/0171-2985-00284

    authors: Prell C,Konstantopoulos N,Heinzelmann B,Frankenberger B,Reinhardt D,Schendel DJ,Krauss-Etschmann S

    更新日期:2003-01-01 00:00:00

  • The CD300 molecules regulate monocyte and dendritic cell functions.

    abstract::The CD300 glycoproteins are a family of related leucocyte surface molecules that modulate a diverse array of cell processes via their paired triggering and inhibitory receptor functions. All family members have a single Ig-V like domain and they share a common evolutionary pathway. At least one member of the family ha...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.imbio.2009.06.004

    authors: Clark GJ,Ju X,Azlan M,Tate C,Ding Y,Hart DN

    更新日期:2009-01-01 00:00:00

  • Biological aspects of tumor necrosis factor.

    abstract::Tumor necrosis factor (TNF) has been determined as an endogenous mediator for endotoxin-induced tumor necrosis. This macrophage product has been biochemically characterized and its protein structure defined by molecular cloning of the TNF gene. Experiments with antibodies to TNF demonstrated that TNF acts as an effect...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(86)80110-3

    authors: Männel DN

    更新日期:1986-09-01 00:00:00

  • Consequences of antigen self-presentation by tumor-specific cytotoxic T cells.

    abstract::CD8-positive cytotoxic T cells (CTL) recognize antigenic peptides in combination with major histocompatibility complex (MHC) class I molecules on the surface of syngeneic antigen presenting cells (APC). In the present paper we show that cells from tumor antigen-specific CTL clones present their cognate antigenic pepti...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/s0171-2985(00)80088-1

    authors: Staege MS,Schneider J,Eulitz M,Scholz S,Bornkamm GW,Wölfel T,Reske-Kunz AB

    更新日期:2000-01-01 00:00:00

  • Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man.

    abstract::Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect...

    journal_title:Immunobiology

    pub_type: 临床试验,杂志文章

    doi:10.1016/S0171-2985(11)80016-1

    authors: Berthold F,Berthold R,Matter I,Reither M,Rother U,Skvaril F,Willems WR

    更新日期:1982-01-01 00:00:00

  • A trypsin-based method for isolating leukocytes from human choriodecidua suitable for immunophenotyping and transcriptome studies.

    abstract::Leukocytes found at the human maternal-fetal interface participate in the inflammatory process associated with both preterm and term labor; therein, effective methods for their isolation that allow further phenotypic and functional analyses are necessary. Leukocyte isolation is usually carried out through scraping or ...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2018.09.001

    authors: MacDonald-Ramos K,Arenas-Hernandez M,Mancilla-Herrera I,Rangel-Escareño C,Vega-Sanchez R

    更新日期:2019-01-01 00:00:00

  • Lymphocyte homing in mice: lack of significant alteration when H-2 antigen expression is moderately modified.

    abstract::The part played by MHC antigens on lymphocyte homing has been investigated by inducing modifications of their expression on lymphoid cells. A significant, though moderate, enhancement of H-2 antigen expression has been observed following in vitro treatment of lymphocytes with alpha-IFN. A decrease has been obtained af...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(84)80073-X

    authors: Navarro J,El Ansary M,Royo C,de Maeyer E,Touraine JL

    更新日期:1984-12-01 00:00:00

  • Antibody response in aged C57BL/6 mice: T helper cells are responsible for the decline of the primary antibody response to a bacterial antigen in aging.

    abstract::One of the most important effects of aging is the decline of immune effectiveness. A study is described here on the primary (IgM) antibody response to phosphorylcholine (PC), an antigen expressed on the surface of the Streptococcus pneumoniae R36a, in aged (18-22 mo.) C57BL/6 mice. Preliminary data showed a significan...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(11)80288-3

    authors: Nicoletti C

    更新日期:1994-02-01 00:00:00

  • Modulation of T cell function by TCR/pMHC binding kinetics.

    abstract::The interaction between the T cell receptor (TCR) and the peptide-MHC complex (pMHC) at the interface between the T cell and the antigen presenting cell (APC) is the main event controlling the specificity of antigen recognition by T cells. It is thought that TCR/pMHC binding kinetics are critical for the selection of ...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.imbio.2005.09.003

    authors: Carreño LJ,González PA,Kalergis AM

    更新日期:2006-01-01 00:00:00

  • Viral infections and allergies.

    abstract::Respiratory viral infections have been implicated in the origin of, protection from and exacerbation of allergy-related symptoms in a variety of ways. Viral infections are closely linked to infantile wheezing. Severe bronchiolitis in early infancy may predispose to chronic childhood asthma as well as allergic sensitiz...

    journal_title:Immunobiology

    pub_type: 杂志文章,评审

    doi:10.1016/j.imbio.2007.03.008

    authors: Xepapadaki P,Papadopoulos NG

    更新日期:2007-01-01 00:00:00

  • Clinical application of partially purified human urinary colony-stimulating factor.

    abstract::Human urinary colony-stimulating factor (CSF-HU) has been partially purified using five purification procedures (preparation II) for clinical use. In phase I study, six healthy volunteers were injected with preparation II of CSF-HU by a single intravenous droplet infusion. Two volunteers received 4 X 10(6) units (U), ...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(86)80100-0

    authors: Motoyoshi K,Ishizaka Y,Miura Y,Takaku F

    更新日期:1986-09-01 00:00:00

  • Induction of IgE and IgG1 in human B cell cultures with staphylococcal superantigens: role of helper T cell interaction, resistance to interferon-gamma.

    abstract::Non-antigen-specific activation of human B lymphocytes for IgE production in vitro requires the presence of interleukin 4 and non-cognate physical interaction with T cells. The latter can be replaced by antibodies directed against the B cells' CD40 structure. Antigen-specific induction of immunoglobulin responses, inc...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(11)80234-2

    authors: Armerding D,van Reijsen FC,Hren A,Mudde GC

    更新日期:1993-07-01 00:00:00

  • CD4 expression is important but not essential for infection with exogenous mouse mammary tumor virus.

    abstract::We studied local events in the popliteal lymph nodes of CD4-deficient mice following foot pad injection with an MMTV strain which carries the gene for a V beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of CD...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(96)80053-2

    authors: Ando Y,Wajjwalku W,Kishihara K,Arai T,Niimi N,Hiromatsu K,Morishima T,Yoshikai Y

    更新日期:1996-08-01 00:00:00

  • Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on induction of experimental autoimmune encephalomyelitis.

    abstract::Carboxypeptidase N (CPN) is a member of the carboxypeptidase family of enzymes that cleave carboxy-terminal lysine and arginine residues from a large number of biologically active peptides and proteins. These enzymes are best known for their roles in modulating the activity of kinins, complement anaphylatoxins and coa...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2013.08.007

    authors: Hu X,Wetsel RA,Ramos TN,Mueller-Ortiz SL,Schoeb TR,Barnum SR

    更新日期:2014-02-01 00:00:00

  • Regulation of expression of the LFA-1 and p150,95 leukocyte integrins: involvement of the CD11a and CD11c gene promoters.

    abstract::Human Lymphocyte Associated Antigen-1 (LFA-1, CD11a/CD18, alpha L/beta 2) and p150,95 (CD11c/CD18, alpha X/beta 2) are cell surface alpha/beta heterodimers that, together with Mac-1 (CD11b/CD18, alpha M/beta 2) comprise the leukocyte-restricted beta 2 subfamily of integrins. LFA-1 is the only integrin expressed on all...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/s0171-2985(11)80560-7

    authors: López-Rodríguez C,Nueda A,Rubio M,Corbí AL

    更新日期:1995-07-01 00:00:00

  • Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing.

    abstract::Paracoccidioides brasiliensis is a dimorphic fungus from the Paracoccidioides genus, which is the causative agent of paracoccidioidomycosis, a chronic, subacute or acute mycosis, with visceral and cutaneous involvement. This disease that is acquired through inhalation primarily attacks the lungs but, can spread to oth...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2015.09.003

    authors: Bachiega TF,Dias-Melicio LA,Fernandes RK,de Almeida Balderramas H,Rodrigues DR,Ximenes VF,de Campos Soares ÂM

    更新日期:2016-02-01 00:00:00

  • Multidirectional interactions in vitro between lymphoid cells from Mls-disparate strains.

    abstract::Chromosome 1 of the mouse carries a number of genes for alloantigens which can be recognized by T cells, among those the mixed lymphocyte stimulation (Mls) locus and the lymphocyte stimulating determinant (Lsd) locus have been described. The Relationship between the antigens coded for by these two loci has been furthe...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(88)80037-8

    authors: Goldbach J,Prahl H,Stäb F,Steinhausen D,Kölsch E

    更新日期:1988-05-01 00:00:00

  • Dendritic cells pulsed with Pythium insidiosum (1,3)(1,6)-β-glucan, Heat-inactivated zoospores and immunotherapy prime naïve T cells to Th1 differentiation in vitro.

    abstract::Pythiosis is a life-threatening disease caused by the fungus-like microorganism Pythium insidiosum that can lead to death if not treated. Since P. insidiosum has particular cell wall characteristics, pythiosis is difficult to treat, as it does not respond well to traditional antifungal drugs. In our study, we investig...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/j.imbio.2017.10.033

    authors: Ledur PC,Tondolo JSM,Jesus FPK,Verdi CM,Loreto ÉS,Alves SH,Santurio JM

    更新日期:2018-03-01 00:00:00

  • A "spontaneous" cold-reactive IgM antibody with anti HLA-B8 specificity in a patient with multiple sclerosis.

    abstract::A case of a 35-year-old female with multiple sclerosis is reported who developed without apparent prior sensitization a lymphocytotoxic antibody with anti-HLA-B8 specificity. The antibody persisted for several years with the same titer. The cytotoxic activity of the patient's serum was contained within the IgM fractio...

    journal_title:Immunobiology

    pub_type: 杂志文章

    doi:10.1016/S0171-2985(82)80002-8

    authors: Lenhard V,Diehm H,Römer W,Rauterberg EW,Kownatzki E,Roelcke D

    更新日期:1982-02-01 00:00:00