当前位置： SCI文献检索 > CANCER CELL期刊下所有文献 > Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells.

Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells.

Abstract：

:T cell engineering is a powerful means to rapidly generate anti-tumor T cells. The costimulatory properties of second-generation chimeric antigen receptors (CARs) determine the overall potency of adoptively transferred T cells. Using an in vivo "stress test" to challenge CD19-targeted T cells, we studied the functionality and persistence imparted by seven different CAR structures providing CD28 and/or 4-1BB costimulation. One configuration, which uses two signaling domains (CD28 and CD3ζ) and the 4-1BB ligand, provided the highest therapeutic efficacy, showing balanced tumoricidal function and increased T cell persistence accompanied by an elevated CD8/CD4 ratio and decreased exhaustion. Remarkably, induction of the IRF7/IFNβ pathway was required for optimal anti-tumor activity. Thus, 1928z-41BBL T cells possess strikingly potent intrinsic and immunomodulatory qualities.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Zhao Z,Condomines M,van der Stegen SJC,Perna F,Kloss CC,Gunset G,Plotkin J,Sadelain M

doi

10.1016/j.ccell.2015.09.004

subject

Has Abstract

pub_date

2015-10-12 00:00:00

pages

415-428

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00335-9

journal_volume

28

pub_type

杂志文章

相关文献

CANCER CELL文献大全
  • A molecular view of anti-ErbB monoclonal antibody therapy.

    abstract：:Abnormal activation of the epidermal growth factor receptor (EGFR) and its homolog HER2 (Neu/ErbB2) has been associated with many human cancers, and monoclonal antibodies targeting EGFR and HER2 are effective anticancer therapies. Structural studies of these receptors and antibodies have revealed much about how they f...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccr.2008.03.010

    authors： Leahy DJ

    更新日期：2008-04-01 00:00:00

  • A TeNaCious foundation for the metastatic niche.

    abstract：:In the July issue of Nature Medicine, Massagué and colleagues define a biphasic role for the extracellular matrix protein tenascin C as a metastatic niche component in lung colonization by breast cancer cells. These results provide a rationale for designing therapies targeting metastatic progression by disrupting its ...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2011.08.004

    authors： Matei I,Ghajar CM,Lyden D

    更新日期：2011-08-16 00:00:00

  • Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia.

    abstract：:Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causi...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2018.03.021

    authors： Churchman ML,Qian M,Te Kronnie G,Zhang R,Yang W,Zhang H,Lana T,Tedrick P,Baskin R,Verbist K,Peters JL,Devidas M,Larsen E,Moore IM,Gu Z,Qu C,Yoshihara H,Porter SN,Pruett-Miller SM,Wu G,Raetz E,Martin PL,Bowman

    更新日期：2018-05-14 00:00:00

  • Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia.

    abstract：:To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements o...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2011.02.008

    authors： Homminga I,Pieters R,Langerak AW,de Rooi JJ,Stubbs A,Verstegen M,Vuerhard M,Buijs-Gladdines J,Kooi C,Klous P,van Vlierberghe P,Ferrando AA,Cayuela JM,Verhaaf B,Beverloo HB,Horstmann M,de Haas V,Wiekmeijer AS,Pike-Over

    更新日期：2011-04-12 00:00:00

  • The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.

    abstract：:Tumors constitute highly suppressive microenvironments in which infiltrating T cells are "exhausted" by inhibitory receptors such as PD-1. Here we identify TIGIT as a coinhibitory receptor that critically limits antitumor and other CD8(+) T cell-dependent chronic immune responses. TIGIT is highly expressed on human an...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2014.10.018

    authors： Johnston RJ,Comps-Agrar L,Hackney J,Yu X,Huseni M,Yang Y,Park S,Javinal V,Chiu H,Irving B,Eaton DL,Grogan JL

    更新日期：2014-12-08 00:00:00

  • Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases.

    abstract：:Mdmx is a critical negative regulator of the p53 pathway that is stoichiometrically limiting in some tissues. Posttranslational modification and degradation of Mdmx after DNA damage have been proposed to be essential for p53 activation. We tested this model in vivo, where critical stoichiometric relationships are pres...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2009.05.008

    authors： Wang YV,Leblanc M,Wade M,Jochemsen AG,Wahl GM

    更新日期：2009-07-07 00:00:00

  • Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.

    abstract：:We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for....

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2020.04.012

    authors： Carrot-Zhang J,Chambwe N,Damrauer JS,Knijnenburg TA,Robertson AG,Yau C,Zhou W,Berger AC,Huang KL,Newberg JY,Mashl RJ,Romanel A,Sayaman RW,Demichelis F,Felau I,Frampton GM,Han S,Hoadley KA,Kemal A,Laird PW,Lazar AJ

    更新日期：2020-05-11 00:00:00

  • Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma.

    abstract：:Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2016.05.020

    authors： Gomes AL,Teijeiro A,Burén S,Tummala KS,Yilmaz M,Waisman A,Theurillat JP,Perna C,Djouder N

    更新日期：2016-07-11 00:00:00

  • Does CSF1R Blockade Turn into Friendly Fire?

    abstract：:In this issue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation of tumor-associated macrophages, but also an accumulation of tumor-infiltrating polymorphonuclear mononuclear cells caused by Cxcl-1 released from cancer-associated fibroblasts. ...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccell.2017.10.012

    authors： Greten TF

    更新日期：2017-11-13 00:00:00

  • Turning on a dimer: new insights into MLL chimeras.

    abstract：:In this issue of Cancer Cell, demonstrate a novel mechanism for the oncogenic activity of MLL chimeric proteins. By providing coiled-coil or other dimerization domains, the cytoplasmic partners of MLL fusion proteins donate a platform for MLL homodimerization, allowing recruitment of accessory factors needed to activa...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/s1535-6108(03)00192-2

    authors： Hsu K,Look AT

    更新日期：2003-08-01 00:00:00

  • Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer.

    abstract：:Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances a...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2020.05.005

    authors： Shen Y,Wang X,Lu J,Salfenmoser M,Wirsik NM,Schleussner N,Imle A,Freire Valls A,Radhakrishnan P,Liang J,Wang G,Muley T,Schneider M,Ruiz de Almodovar C,Diz-Muñoz A,Schmidt T

    更新日期：2020-06-08 00:00:00

  • Tumor type-dependent function of the par3 polarity protein in skin tumorigenesis.

    abstract：:Cell polarization is crucial during development and tissue homeostasis and is regulated by conserved proteins of the Scribble, Crumbs, and Par complexes. In mouse skin tumorigenesis, Par3 deficiency results in reduced papilloma formation and growth. Par3 mediates its tumor-promoting activity through regulation of grow...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2012.08.004

    authors： Iden S,van Riel WE,Schäfer R,Song JY,Hirose T,Ohno S,Collard JG

    更新日期：2012-09-11 00:00:00

  • Metastatic colon cancer cells negotiate the intravasation Notch.

    abstract：:In this issue of Cancer Cell, Sonoshita et al. report that Aes/Grg5 prevents metastasis of colorectal cancer cells by sequestering and inactivating Notch transcriptional effectors in distinct nuclear foci. Loss of Aes/Grg5 in invasive cancer cells where Notch is activated by stroma-expressed ligands promotes invasion,...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccr.2011.01.003

    authors： Christofori G

    更新日期：2011-01-18 00:00:00

  • Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.

    abstract：:Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not b...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2011.06.001

    authors： Moran-Crusio K,Reavie L,Shih A,Abdel-Wahab O,Ndiaye-Lobry D,Lobry C,Figueroa ME,Vasanthakumar A,Patel J,Zhao X,Perna F,Pandey S,Madzo J,Song C,Dai Q,He C,Ibrahim S,Beran M,Zavadil J,Nimer SD,Melnick A,Godley LA

    更新日期：2011-07-12 00:00:00

  • The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation.

    abstract：:Neuroblastoma is an embryonal tumor of the sympathetic nervous system and the most common extracranial tumor of childhood. By sequencing transcriptomes of low- and high-risk neuroblastomas, we detected differentially expressed annotated and nonannotated long noncoding RNAs (lncRNAs). We identified a lncRNA neuroblasto...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2014.09.014

    authors： Pandey GK,Mitra S,Subhash S,Hertwig F,Kanduri M,Mishra K,Fransson S,Ganeshram A,Mondal T,Bandaru S,Ostensson M,Akyürek LM,Abrahamsson J,Pfeifer S,Larsson E,Shi L,Peng Z,Fischer M,Martinsson T,Hedborg F,Kogner P,

    更新日期：2014-11-10 00:00:00

  • ADORA1 Inhibition Promotes Tumor Immune Evasion by Regulating the ATF3-PD-L1 Axis.

    abstract：:Here, we show that tumor ADORA1 deletion suppresses cell growth in human melanoma cell lines in vitro and tumor development in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PD-L1 levels, which inactivates cocultured T cells in vitro, compromises anti-tumor immunity in vivo, an...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2020.02.006

    authors： Liu H,Kuang X,Zhang Y,Ye Y,Li J,Liang L,Xie Z,Weng L,Guo J,Li H,Ma F,Chen X,Zhao S,Su J,Yang N,Fang F,Xie Y,Tao J,Zhang J,Chen M,Peng C,Sun L,Zhang X,Liu J,Han L,Xu X,Hung MC,Chen X

    更新日期：2020-03-16 00:00:00

  • Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7.

    abstract：:Monosomy 7 and interstitial deletion of 7q (-7/7q-) are well-recognized nonrandom chromosomal abnormalities frequently found among patients with myelodysplastic syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the 7q21.3...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2013.08.011

    authors： Nagamachi A,Matsui H,Asou H,Ozaki Y,Aki D,Kanai A,Takubo K,Suda T,Nakamura T,Wolff L,Honda H,Inaba T

    更新日期：2013-09-09 00:00:00

  • Differential utilization of two ATP-generating pathways is regulated by p53.

    abstract：:A fundamental property of cancer cells is the preferential utilization of glycolysis over aerobic respiration to produce ATP. Renewed interest in understanding the mechanism underlying this metabolic shift in energy production is broadening our understanding of the relationship between cancer and cellular metabolism. ...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2006.06.014

    authors： Assaily W,Benchimol S

    更新日期：2006-07-01 00:00:00

  • ILF2 Is a Regulator of RNA Splicing and DNA Damage Response in 1q21-Amplified Multiple Myeloma.

    abstract：:Amplification of 1q21 occurs in approximately 30% of de novo and 70% of relapsed multiple myeloma (MM) and is correlated with disease progression and drug resistance. Here, we provide evidence that the 1q21 amplification-driven overexpression of ILF2 in MM promotes tolerance of genomic instability and drives resistanc...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2017.05.011

    authors： Marchesini M,Ogoti Y,Fiorini E,Aktas Samur A,Nezi L,D'Anca M,Storti P,Samur MK,Ganan-Gomez I,Fulciniti MT,Mistry N,Jiang S,Bao N,Marchica V,Neri A,Bueso-Ramos C,Wu CJ,Zhang L,Liang H,Peng X,Giuliani N,Draetta G

    更新日期：2017-07-10 00:00:00

  • CHAF1B Overexpression: A Brake for the Differentiation of Leukemia Cells.

    abstract：:In this issue of Cancer Cell, Volk et al. report that overexpression of CHAF1B displaces myeloid transcription factors from chromatin, and deletion of CHAF1B promotes differentiation of leukemia cells and suppresses leukemogenesis in a murine model, revealing a causal role of and an unexpected mechanism for CHAF1B ove...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccell.2018.10.011

    authors： Li Q,Zhang X,Zhang Z

    更新日期：2018-11-12 00:00:00

  • No need for constant help: human IgG2 antibodies have an autonomous agonistic activity for immunotherapy of cancer.

    abstract：:Agonistic antibodies specific for members of the tumor necrosis factor receptor protein family hold great promise for immunotherapy of cancer. In this issue of Cancer Cell, White and colleagues provide evidence that the human IgG2 subclass may represent a superior backbone for the use of these antibodies in human ther...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccell.2014.12.010

    authors： Lux A,Nimmerjahn F

    更新日期：2015-01-12 00:00:00

  • The ups and downs of SRC regulation: tumor suppression by Cbp.

    abstract：:Tight control of the tyrosine kinase activity of c-Src is critical for regulating its oncogenic potential. In a recent issue of Molecular Cell, Oneyama et al. (2008a) report that the membrane-bound adaptor protein Cbp (also known as PAG) can suppress c-Src-mediated cell transformation and tumorigenesis by binding and ...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2008.05.011

    authors： Resh MD

    更新日期：2008-06-01 00:00:00

  • A common pathway for genetic events leading to pheochromocytoma.

    abstract：:Mutations in VHL, RET, NF1, SDHB, SDHC, and SDHD can give rise to pheochromocytoma/paraganglioma. These different genetic lesions may all act by decreasing the activity of a 2-oxoglutarate-dependent oxygenase, SM-20/EglN3/PHD3, resulting in reduced apoptosis of neural crest cells during development. ...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccr.2005.07.012

    authors： Maxwell PH

    更新日期：2005-08-01 00:00:00

  • Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency.

    abstract：:Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccell.2017.08.005

    authors： Hurst CD,Alder O,Platt FM,Droop A,Stead LF,Burns JE,Burghel GJ,Jain S,Klimczak LJ,Lindsay H,Roulson JA,Taylor CF,Thygesen H,Cameron AJ,Ridley AJ,Mott HR,Gordenin DA,Knowles MA

    更新日期：2017-11-13 00:00:00

  • A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases.

    abstract：:Transcriptional profiling of two isogenic models of transformation identifies a gene signature linking cancer with inflammatory and metabolic diseases. In accord with this common transcriptional program, many drugs used for treatment of diabetes and cardiovascular diseases inhibit transformation and tumor growth. Unex...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2010.01.022

    authors： Hirsch HA,Iliopoulos D,Joshi A,Zhang Y,Jaeger SA,Bulyk M,Tsichlis PN,Shirley Liu X,Struhl K

    更新日期：2010-04-13 00:00:00

  • Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes.

    abstract：:We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosph...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2004.05.022

    authors： Vadlamudi RK,Bagheri-Yarmand R,Yang Z,Balasenthil S,Nguyen D,Sahin AA,den Hollander P,Kumar R

    更新日期：2004-06-01 00:00:00

  • Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors.

    abstract：:Loss of p53 is considered to allow progression of colorectal tumors from the adenoma to the carcinoma stage. Using mice with an intestinal epithelial cell (IEC)-specific p53 deletion, we demonstrate that loss of p53 alone is insufficient to initiate intestinal tumorigenesis but markedly enhances carcinogen-induced tum...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2012.11.014

    authors： Schwitalla S,Ziegler PK,Horst D,Becker V,Kerle I,Begus-Nahrmann Y,Lechel A,Rudolph KL,Langer R,Slotta-Huspenina J,Bader FG,Prazeres da Costa O,Neurath MF,Meining A,Kirchner T,Greten FR

    更新日期：2013-01-14 00:00:00

  • Short hairpin RNA screen reveals bromodomain proteins as novel targets in acute myeloid leukemia.

    abstract：:Targeting chromatin regulators for the treatment of malignancies has shown great promise, but also revealed significant challenges. By employing an elegant shRNA screen and a selective pharmacological inhibitor, a recent study published in Nature establishes the bromodomain protein Brd4 as novel target in acute myeloi...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2011.08.019

    authors： Blobel GA,Kalota A,Sanchez PV,Carroll M

    更新日期：2011-09-13 00:00:00

  • Chromosomal instability in mouse metastatic pancreatic cancer--it's Kras and Tp53 after all.

    abstract：:A human pancreatic cancer progression model from intraepithelial neoplasia to ductal adenocarcinoma has been proposed. This process has been modeled in the mouse by activation of mutant Kras in pancreatic progenitor cells. In this issue of Cancer Cell, present a modification of their initial model by introducing a mut...

    journal_title：Cancer cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.ccr.2005.04.025

    authors： Siveke JT,Schmid RM

    更新日期：2005-05-01 00:00:00

  • Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras.

    abstract：:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to onco...

    journal_title：Cancer cell

    pub_type： 杂志文章

    doi：10.1016/j.ccr.2009.09.027

    authors： Gidekel Friedlander SY,Chu GC,Snyder EL,Girnius N,Dibelius G,Crowley D,Vasile E,DePinho RA,Jacks T

    更新日期：2009-11-06 00:00:00