[English] 日本語
Yorodumi
- PDB-9bdo: Crystal structure of anti-abTCR NANOBODY VHH -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9bdo
TitleCrystal structure of anti-abTCR NANOBODY VHH
ComponentsTCE01 NANOBODY VHH
KeywordsANTITUMOR PROTEIN / NANOBODY / VHH / antibody / TCR
Function / homologyACETATE ION
Function and homology information
Biological speciesLama glama (llama)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.948 Å
AuthorsQiu, Y.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: Mol Cancer Ther / Year: 2025
Title: Identification and non-clinical characterization of SAR444200, a novel anti-GPC3 NANOBODY® T-cell engager, for the treatment of GPC3+ solid tumors.
Authors: Paolo Meoni / Ana Paula B Vintém / Virna F Cortez-Retamozo / Jasper Jacobs / Evelyn De Tavernier / Paola Fiorentini / Diane Van Hoorick / Joseph D Batchelor / Egor Svidritskiy / Yu Qiu / ...Authors: Paolo Meoni / Ana Paula B Vintém / Virna F Cortez-Retamozo / Jasper Jacobs / Evelyn De Tavernier / Paola Fiorentini / Diane Van Hoorick / Joseph D Batchelor / Egor Svidritskiy / Yu Qiu / Eline Dejonckheere / Aiqun Li / Lily I Pao / Marie-Ange Buyse /
Abstract: T-cell engager (TCE) immunotherapy has demonstrated significant clinical activity in multiple cancers by inducing co-engagement of T-cells and tumor cells, resulting in T-cell activation and T-cell- ...T-cell engager (TCE) immunotherapy has demonstrated significant clinical activity in multiple cancers by inducing co-engagement of T-cells and tumor cells, resulting in T-cell activation and T-cell-dependent cellular cytotoxicity (TDCC) against tumor cells. Current-generation TCEs are predominantly composed of antibody-based binding domains targeting the CD3e molecule of the T-cell antigen receptor (TCR)/CD3 complex on T-cells and a tumor-associated antigen on tumor cells. However, limitations of this approach include cytokine release syndrome and a limited therapeutic window. Here, we report the generation and preclinical evaluation of SAR444200, the first NANOBODY®-based TCE clinical candidate binding to TCRαβ and GPC3 to co-engage T-cells and GPC3+ tumor cells, causing TDCC. SAR444200 bound with nanomolar to picomolar affinity to TCRαβ and GPC3 respectively and induced in vitro TDCC against multiple human tumor cell lines with differential GPC3 expression with picomolar potency. In vivo analysis using human cancer cell line-derived (HuH-7 and HepG2) xenografts in immunodeficient mice showed complete tumor regression at doses starting from 0.7 mg/kg. In exploratory non-human primate studies, intravenous administration of SAR444200 was well tolerated up to 8 mg/kg and exhibited greater than dose-proportional clearances and dose-proportional maximum concentrations across the tested dose range. The highly potent and efficacious activity of SAR444200 in diverse models of GPC3+ tumors and the extremely wide tolerated dose range merits further development of this compound. Furthermore, NANOBODY®-based TCEs developed using an anti-TCRαβ moiety may have specific advantages for the development of TCEs.
History
DepositionApr 12, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 16, 2025Provider: repository / Type: Initial release
Revision 1.1Oct 22, 2025Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: TCE01 NANOBODY VHH
B: TCE01 NANOBODY VHH
C: TCE01 NANOBODY VHH
hetero molecules


Theoretical massNumber of molelcules
Total (without water)39,77510
Polymers39,1853
Non-polymers5907
Water2,792155
1
A: TCE01 NANOBODY VHH
hetero molecules


Theoretical massNumber of molelcules
Total (without water)13,2543
Polymers13,0621
Non-polymers1922
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: TCE01 NANOBODY VHH


Theoretical massNumber of molelcules
Total (without water)13,0621
Polymers13,0621
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: TCE01 NANOBODY VHH
hetero molecules


Theoretical massNumber of molelcules
Total (without water)13,4606
Polymers13,0621
Non-polymers3985
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)96.949, 70.725, 54.403
Angle α, β, γ (deg.)90.00, 94.86, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Antibody TCE01 NANOBODY VHH


Mass: 13061.505 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Production host: Komagataella pastoris (fungus)
#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H3O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 155 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.37 Å3/Da / Density % sol: 48.13 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.18 M Li2SO4, 10 mM trimethylTMamine, 90 mM NaAc (pH 4.4), and 27% (w/v) PEG8000.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 1.0334 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 6, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0334 Å / Relative weight: 1
ReflectionResolution: 1.948→57.12 Å / Num. obs: 26641 / % possible obs: 99.5 % / Redundancy: 3.6 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 4.2
Reflection shellResolution: 1.95→2 Å / Redundancy: 3.4 % / Rmerge(I) obs: 0.731 / Num. unique obs: 1953 / % possible all: 99.1

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (19-MAR-2020)refinement
HKL-2000data scaling
HKL-2000data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.948→57.06 Å / Cor.coef. Fo:Fc: 0.918 / Cor.coef. Fo:Fc free: 0.913 / SU R Cruickshank DPI: 0.182 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.181 / SU Rfree Blow DPI: 0.154 / SU Rfree Cruickshank DPI: 0.156
RfactorNum. reflection% reflectionSelection details
Rfree0.2415 1296 4.87 %RANDOM
Rwork0.2113 ---
obs0.2127 26611 99 %-
Displacement parametersBiso mean: 46.45 Å2
Baniso -1Baniso -2Baniso -3
1-7.1569 Å20 Å29.4206 Å2
2---12.8068 Å20 Å2
3---5.6499 Å2
Refine analyzeLuzzati coordinate error obs: 0.32 Å
Refinement stepCycle: LAST / Resolution: 1.948→57.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2718 0 35 155 2908
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0082812HARMONIC2
X-RAY DIFFRACTIONt_angle_deg13809HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d934SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes475HARMONIC5
X-RAY DIFFRACTIONt_it2812HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.6
X-RAY DIFFRACTIONt_other_torsion18.48
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion344SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2299SEMIHARMONIC4
LS refinement shellResolution: 1.95→1.96 Å / Total num. of bins used: 51
RfactorNum. reflection% reflection
Rfree0.233 -5.07 %
Rwork0.2215 506 -
all0.222 533 -
obs--88.44 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.58021.68591.69432.62790.54633.3214-0.071-0.06010.203-0.15230.08160.2707-0.0703-0.3032-0.0106-0.0943-0.0284-0.03590.00290.0461-0.052524.88658.937912.4403
26.9407-0.50765.03832.2025-0.38217.20740.34440.7479-0.3826-0.34260.06020.02450.53910.7622-0.4046-0.03760.0349-0.0789-0.0272-0.0854-0.1118-4.339126.091913.3038
37.86491.33292.03232.22880.09363.6289-0.0443-0.07580.17080.0708-0.1103-0.0297-0.1640.10590.1547-0.0805-0.0385-0.0123-0.01510.0228-0.12262.6119-8.258613.4234
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }
3X-RAY DIFFRACTION3{ C|* }

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more