Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response.

Abstract:

:T cells expressing CD19-targeting chimeric antigen receptors (CARs) reveal high efficacy in the treatment of B cell malignancies. Here, we report that T cell receptor fusion constructs (TRuCs) comprising an antibody-based binding domain fused to T cell receptor (TCR) subunits can effectively reprogram an intact TCR complex to recognize tumor surface antigens. Unlike CARs, TRuCs become a functional component of the TCR complex. TRuC-T cells kill tumor cells as potently as second-generation CAR-T cells, but at significant lower cytokine release and despite the absence of an extra co-stimulatory domain. TRuC-T cells demonstrate potent anti-tumor activity in both liquid and solid tumor xenograft models. In several models, TRuC-T cells are more efficacious than respective CAR-T cells. TRuC-T cells are shown to engage the signaling capacity of the entire TCR complex in an HLA-independent manner.

journal_name

Nat Commun

journal_title

Nature communications

authors

Baeuerle PA,Ding J,Patel E,Thorausch N,Horton H,Gierut J,Scarfo I,Choudhary R,Kiner O,Krishnamurthy J,Le B,Morath A,Baldeviano GC,Quinn J,Tavares P,Wei Q,Weiler S,Maus MV,Getts D,Schamel WW,Hofmeister R

doi

10.1038/s41467-019-10097-0

subject

Has Abstract

pub_date

2019-05-07 00:00:00

pages

2087

issue

1

issn

2041-1723

pii

10.1038/s41467-019-10097-0

journal_volume

10

pub_type

杂志文章
  • Adrenal hormones mediate disease tolerance in malaria.

    abstract::Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06986-5

    authors: Vandermosten L,Pham TT,Knoops S,De Geest C,Lays N,Van der Molen K,Kenyon CJ,Verma M,Chapman KE,Schuit F,De Bosscher K,Opdenakker G,Van den Steen PE

    更新日期:2018-10-30 00:00:00

  • Expansion of a superconducting vortex core into a diffusive metal.

    abstract::Vortices in quantum condensates exist owing to a macroscopic phase coherence. Here we show, both experimentally and theoretically, that a quantum vortex with a well-defined core can exist in a rather thick normal metal, proximized with a superconductor. Using scanning tunneling spectroscopy we reveal a proximity vorte...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04582-1

    authors: Stolyarov VS,Cren T,Brun C,Golovchanskiy IA,Skryabina OV,Kasatonov DI,Khapaev MM,Kupriyanov MY,Golubov AA,Roditchev D

    更新日期:2018-06-11 00:00:00

  • Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts.

    abstract::Understanding the impact of rare variants is essential to understanding human health. We analyze rare (MAF < 0.1%) variants against 4264 phenotypes in 49,960 exome-sequenced individuals from the UK Biobank and 1934 phenotypes (1821 overlapping with UK Biobank) in 21,866 members of the Healthy Nevada Project (HNP) coho...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14288-y

    authors: Cirulli ET,White S,Read RW,Elhanan G,Metcalf WJ,Tanudjaja F,Fath DM,Sandoval E,Isaksson M,Schlauch KA,Grzymski JJ,Lu JT,Washington NL

    更新日期:2020-01-28 00:00:00

  • Modeling medulloblastoma in vivo and with human cerebellar organoids.

    abstract::Medulloblastoma (MB) is the most common malignant brain tumor in children and among the subtypes, Group 3 MB has the worst outcome. Here, we perform an in vivo, patient-specific screen leading to the identification of Otx2 and c-MYC as strong Group 3 MB inducers. We validated our findings in human cerebellar organoids...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13989-3

    authors: Ballabio C,Anderle M,Gianesello M,Lago C,Miele E,Cardano M,Aiello G,Piazza S,Caron D,Gianno F,Ciolfi A,Pedace L,Mastronuzzi A,Tartaglia M,Locatelli F,Ferretti E,Giangaspero F,Tiberi L

    更新日期:2020-01-29 00:00:00

  • High-performance light-driven heterogeneous CO2 catalysis with near-unity selectivity on metal phosphides.

    abstract::Akin to single-site homogeneous catalysis, a long sought-after goal is to achieve reaction site precision in heterogeneous catalysis for chemical control over patterns of activity, selectivity and stability. Herein, we report on metal phosphides as a class of material capable of realizing these attributes and unlock t...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18943-2

    authors: Xu YF,Duchesne PN,Wang L,Tavasoli A,Jelle AA,Xia M,Liao JF,Kuang DB,Ozin GA

    更新日期:2020-10-13 00:00:00

  • Molecular structure of promoter-bound yeast TFIID.

    abstract::Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBP-associate factors (Tafs) providing regulatory and chromatin binding functions. Here we present the cryo-electron microscopy structure of promot...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07096-y

    authors: Kolesnikova O,Ben-Shem A,Luo J,Ranish J,Schultz P,Papai G

    更新日期:2018-11-07 00:00:00

  • A Pseudomonas T6SS effector recruits PQS-containing outer membrane vesicles for iron acquisition.

    abstract::Iron sequestration by host proteins contributes to the defence against bacterial pathogens, which need iron for their metabolism and virulence. A Pseudomonas aeruginosa mutant lacking all three known iron acquisition systems retains the ability to grow in media containing iron chelators, suggesting the presence of add...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14888

    authors: Lin J,Zhang W,Cheng J,Yang X,Zhu K,Wang Y,Wei G,Qian PY,Luo ZQ,Shen X

    更新日期:2017-03-28 00:00:00

  • DNA replication timing and higher-order nuclear organization determine single-nucleotide substitution patterns in cancer genomes.

    abstract::Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and can...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2502

    authors: Liu L,De S,Michor F

    更新日期:2013-01-01 00:00:00

  • High rate and stable cycling of lithium metal anode.

    abstract::Lithium metal is an ideal battery anode. However, dendrite growth and limited Coulombic efficiency during cycling have prevented its practical application in rechargeable batteries. Herein, we report that the use of highly concentrated electrolytes composed of ether solvents and the lithium bis(fluorosulfonyl)imide sa...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7362

    authors: Qian J,Henderson WA,Xu W,Bhattacharya P,Engelhard M,Borodin O,Zhang JG

    更新日期:2015-02-20 00:00:00

  • Tolerance induction to human stem cell transplants with extension to their differentiated progeny.

    abstract::There is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants differ from conventional...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6629

    authors: Lui KO,Howie D,Ng SW,Liu S,Chien KR,Waldmann H

    更新日期:2014-12-01 00:00:00

  • Biogeography and habitat modelling of high-alpine bacteria.

    abstract::Soil microorganisms dominate terrestrial biogeochemical cycles; however, we know very little about their spatial distribution and how changes in the distributions of specific groups of microbes translate into landscape and global patterns of biogeochemical processes. In this paper, we use a nested sampling scheme at s...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1055

    authors: King AJ,Freeman KR,McCormick KF,Lynch RC,Lozupone C,Knight R,Schmidt SK

    更新日期:2010-08-10 00:00:00

  • Author Correction: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 已发布勘误

    doi:10.1038/s41467-019-10951-1

    authors: International Multiple Sclerosis Genetics Consortium.

    更新日期:2019-07-01 00:00:00

  • FAM111A protects replication forks from protein obstacles via its trypsin-like domain.

    abstract::Persistent protein obstacles on genomic DNA, such as DNA-protein crosslinks (DPCs) and tight nucleoprotein complexes, can block replication forks. DPCs can be removed by the proteolytic activities of the metalloprotease SPRTN or the proteasome in a replication-coupled manner; however, additional proteolytic mechanisms...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15170-7

    authors: Kojima Y,Machida Y,Palani S,Caulfield TR,Radisky ES,Kaufmann SH,Machida YJ

    更新日期:2020-03-12 00:00:00

  • Templated growth of oriented layered hybrid perovskites on 3D-like perovskites.

    abstract::The manipulation of crystal orientation from the thermodynamic equilibrium states is desired in layered hybrid perovskite films to direct charge transport and enhance the perovskite devices performance. Here we report a templated growth mechanism of layered perovskites from 3D-like perovskites which can be a general d...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13856-1

    authors: Wang J,Luo S,Lin Y,Chen Y,Deng Y,Li Z,Meng K,Chen G,Huang T,Xiao S,Huang H,Zhou C,Ding L,He J,Huang J,Yuan Y

    更新日期:2020-01-29 00:00:00

  • Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer.

    abstract::Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic Wnt signalling could be specifically targeted remains controversial. Here we examine the requirement of BCL9/9l, constituents of the Wnt-enhanceosome, for i...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08586-3

    authors: Gay DM,Ridgway RA,Müller M,Hodder MC,Hedley A,Clark W,Leach JD,Jackstadt R,Nixon C,Huels DJ,Campbell AD,Bird TG,Sansom OJ

    更新日期:2019-02-13 00:00:00

  • Cobalt-centred boron molecular drums with the highest coordination number in the CoB16- cluster.

    abstract::The electron deficiency and strong bonding capacity of boron have led to a vast variety of molecular structures in chemistry and materials science. Here we report the observation of highly symmetric cobalt-centered boron drum-like structures of CoB16(-), characterized by photoelectron spectroscopy and ab initio calcul...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9654

    authors: Popov IA,Jian T,Lopez GV,Boldyrev AI,Wang LS

    更新日期:2015-10-12 00:00:00

  • Addendum: Precise tuning of gene expression levels in mammalian cells.

    abstract::Following re-sequencing of the miSFIT constructs used in the paper, two of the construct variants inserted into the 3'UTR of PD-1, namely '12C' and '17A, 18G', have been found to contain additional insertions not present in the other construct variants. The data points corresponding to these constructs in Figs. 2c, f ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10615-0

    authors: Michaels YS,Barnkob MB,Barbosa H,Baeumler TA,Thompson MK,Andre V,Colin-York H,Fritzsche M,Gileadi U,Sheppard HM,Knapp DJHF,Milne TA,Cerundolo V,Fulga TA

    更新日期:2019-06-10 00:00:00

  • Conformational gating of DNA conductance.

    abstract::DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductan...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9870

    authors: Artés JM,Li Y,Qi J,Anantram MP,Hihath J

    更新日期:2015-12-09 00:00:00

  • Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan.

    abstract::Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09329-0

    authors: Chen DQ,Cao G,Chen H,Argyopoulos CP,Yu H,Su W,Chen L,Samuels DC,Zhuang S,Bayliss GP,Zhao S,Yu XY,Vaziri ND,Wang M,Liu D,Mao JR,Ma SX,Zhao J,Zhang Y,Shang YQ,Kang H,Ye F,Cheng XH,Li XR,Zhang L,Meng MX,G

    更新日期:2019-04-01 00:00:00

  • Structural insights into chaperone addiction of toxin-antitoxin systems.

    abstract::SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08747-4

    authors: Guillet V,Bordes P,Bon C,Marcoux J,Gervais V,Sala AJ,Dos Reis S,Slama N,Mares-Mejía I,Cirinesi AM,Maveyraud L,Genevaux P,Mourey L

    更新日期:2019-02-15 00:00:00

  • Ultrasensitive visual read-out of nucleic acids using electrocatalytic fluid displacement.

    abstract::Diagnosis of disease outside of sophisticated laboratories urgently requires low-cost, user-friendly devices. Disposable, instrument-free testing devices are used for home and physician office testing, but are limited in applicability to a small class of highly abundant analytes. Direct, unambiguous visual read-out is...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7978

    authors: Besant JD,Das J,Burgess IB,Liu W,Sargent EH,Kelley SO

    更新日期:2015-04-22 00:00:00

  • A diverse intrinsic antibiotic resistome from a cave bacterium.

    abstract::Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an un...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13803

    authors: Pawlowski AC,Wang W,Koteva K,Barton HA,McArthur AG,Wright GD

    更新日期:2016-12-08 00:00:00

  • High conductance values in π-folded molecular junctions.

    abstract::Folding processes play a crucial role in the development of function in biomacromolecules. Recreating this feature on synthetic systems would not only allow understanding and reproducing biological functions but also developing new functions. This has inspired the development of conformationally ordered synthetic olig...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15195

    authors: Carini M,Ruiz MP,Usabiaga I,Fernández JA,Cocinero EJ,Melle-Franco M,Diez-Perez I,Mateo-Alonso A

    更新日期:2017-05-18 00:00:00

  • Patients with basal ganglia damage show preserved learning in an economic game.

    abstract::Both basal ganglia (BG) and orbitofrontal cortex (OFC) have been widely implicated in social and non-social decision-making. However, unlike OFC damage, BG pathology is not typically associated with disturbances in social functioning. Here we studied the behavior of patients with focal lesions to either BG or OFC in a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08766-1

    authors: Zhu L,Jiang Y,Scabini D,Knight RT,Hsu M

    更新日期:2019-02-18 00:00:00

  • Terahertz field control of in-plane orbital order in La(0.5)Sr(1.5)MnO4.

    abstract::In-plane anisotropic ground states are ubiquitous in correlated solids such as pnictides, cuprates and manganites. They can arise from doping Mott insulators and compete with phases such as superconductivity; however, their origins are debated. Strong coupling between lattice, charge, orbital and spin degrees of freed...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9175

    authors: Miller TA,Chhajlany RW,Tagliacozzo L,Green B,Kovalev S,Prabhakaran D,Lewenstein M,Gensch M,Wall S

    更新日期:2015-09-18 00:00:00

  • In situ spectroscopy-guided engineering of rhodium single-atom catalysts for CO oxidation.

    abstract::Single-atom catalysts have recently been applied in many applications such as CO oxidation. Experimental in situ investigations into this reaction, however, are limited. Hereby, we present a suite of operando/in situ spectroscopic experiments for structurally well-defined atomically dispersed Rh on phosphotungstic aci...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09188-9

    authors: Hülsey MJ,Zhang B,Ma Z,Asakura H,Do DA,Chen W,Tanaka T,Zhang P,Wu Z,Yan N

    更新日期:2019-03-22 00:00:00

  • Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling.

    abstract::Non-aromatic nitrogen- and oxygen-containing heterocycles such as piperidines and pyrans are prevalent components of natural products and pharmaceutical drugs. Although it has been a workhorse as a synthetic method for assembling unsaturated sp(2)-hybridized substrates, transition metal-catalysed cross-coupling chemis...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6474

    authors: Ding J,Rybak T,Hall DG

    更新日期:2014-11-18 00:00:00

  • Frustrated supercritical collapse in tunable charge arrays on graphene.

    abstract::The photon-like behavior of electrons in graphene causes unusual confinement properties that depend strongly on the geometry and strength of the surrounding potential. We report bottom-up synthesis of atomically-precise one-dimensional (1D) arrays of point charges on graphene that allow exploration of a new type of su...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-08371-2

    authors: Lu J,Tsai HZ,Tatan AN,Wickenburg S,Omrani AA,Wong D,Riss A,Piatti E,Watanabe K,Taniguchi T,Zettl A,Pereira VM,Crommie MF

    更新日期:2019-01-29 00:00:00

  • MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes.

    abstract::Colorectal cancer (CRC) transcriptional subtypes have been recently identified by gene expression profiling. Here we describe an analytical pipeline, microRNA master regulator analysis (MMRA), developed to search for microRNAs potentially driving CRC subtypes. Starting from a microRNA-mRNA tumour expression data set, ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms9878

    authors: Cantini L,Isella C,Petti C,Picco G,Chiola S,Ficarra E,Caselle M,Medico E

    更新日期:2015-11-17 00:00:00

  • Epidermal phospholipase Cδ1 regulates granulocyte counts and systemic interleukin-17 levels in mice.

    abstract::Phospholipase C is a key enzyme in phosphoinositide turnover. Although its functions have been extensively studied at the cellular level, many questions remain concerning its functions at the organ and individual animal levels. Here we demonstrate that mice lacking phospholipase Cδ1 develop granulocytosis associated w...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1960

    authors: Kanemaru K,Nakamura Y,Sato K,Kojima R,Takahashi S,Yamaguchi M,Ichinohe M,Kiyonari H,Shioi G,Kabashima K,Nakahigashi K,Asagiri M,Jamora C,Yamaguchi H,Fukami K

    更新日期:2012-07-17 00:00:00