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- EMDB-71123: CD73-Sym024 focused map 1 -

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Basic information

Entry
Database: EMDB / ID: EMD-71123
TitleCD73-Sym024 focused map 1
Map data
Sample
  • Complex: CD73 dimer bound to antibody Sym024
KeywordsAntigen-Antibody Complex / Drug Target / HYDROLASE
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.66 Å
AuthorsArmbruster E / Bansia H / Des Georges A
Funding support1 items
OrganizationGrant numberCountry
Other private
CitationJournal: Clin Cancer Res / Year: 2026
Title: Sym024 Interacts with a Unique Epitope on the CD73 Homodimer, Favoring Effective Bivalent Binding to Improve Anti-PD-1 Therapy.
Authors: Janus S Jakobsen / Michael M Grandal / Randi W Hansen / Harsh Bansia / Emily Armbruster / Isabelle Theret / Niels Jørgen Ø Skartved / Rikke Hald / Maria C Melander / Anne Worsaae / Matteo ...Authors: Janus S Jakobsen / Michael M Grandal / Randi W Hansen / Harsh Bansia / Emily Armbruster / Isabelle Theret / Niels Jørgen Ø Skartved / Rikke Hald / Maria C Melander / Anne Worsaae / Matteo Riva / Kristian Reckzeh / Laurent Vuillard / Johan Lantto / Amedee des Georges / Camilla Fröhlich /
Abstract: PURPOSE: Adenosine signaling may be a central immunosuppressive mechanism in several cancers, and blockade of the rate-limiting CD73 adenosine monophosphate (AMP)-to-adenosine enzyme has been ...PURPOSE: Adenosine signaling may be a central immunosuppressive mechanism in several cancers, and blockade of the rate-limiting CD73 adenosine monophosphate (AMP)-to-adenosine enzyme has been demonstrated to improve the clinical efficacy of programmed cell death protein (ligand) 1 [PD-(L)1] immune therapy. However, deep inhibition of CD73 activity could prove difficult in tumor environments with a constant AMP supply and high CD73 levels. In this study, we sought to identify, characterize, and benchmark a novel antagonistic anti-CD73 antibody, Sym024 (S95024), and to structurally decode its mode of action.
EXPERIMENTAL DESIGN: Sym024, selected via functional antibody repertoire screening, was tested against benchmark anti-CD73 antibodies in primary cell, cell line in vitro binding, CD73 enzymatic ...EXPERIMENTAL DESIGN: Sym024, selected via functional antibody repertoire screening, was tested against benchmark anti-CD73 antibodies in primary cell, cell line in vitro binding, CD73 enzymatic activity, and T-cell activation assays. Its in vivo tumor growth inhibition was examined in transplanted human or mouse tumors in immunocompetent or immunodeficient mice, and intratumoral enzymatic inhibition and immune cell recruitment were assessed. We investigated the Sym024-CD73 interaction using surface plasmon resonance, cryogenic electron microscopy, site-directed mutagenesis, and population-level complex formation through size-exclusion chromatography with light scatter mass detection. Preclinical safety and pharmacokinetics (PK) were assessed in monkeys.
RESULTS: Sym024 effectively blocked CD73 across a large range of enzyme expression levels, comparing favorably with benchmark anti-CD73 antibodies; it improved the efficacy of PD-1 blockade in vitro ...RESULTS: Sym024 effectively blocked CD73 across a large range of enzyme expression levels, comparing favorably with benchmark anti-CD73 antibodies; it improved the efficacy of PD-1 blockade in vitro as well as in vivo. Our structural data indicate that a unique one-to-one Sym024-CD73 interaction engenders this comprehensive inhibition. No preclinical safety flags were observed, and the PK profile of Sym024 supported a standard clinical dosing regimen.
CONCLUSIONS: The comprehensive CD73 inhibition exhibited by Sym024 may improve the efficacy of anti-PD-(L)1/anti-CD73 combination treatment.
History
DepositionJun 10, 2025-
Header (metadata) releaseJan 7, 2026-
Map releaseJan 7, 2026-
UpdateMar 25, 2026-
Current statusMar 25, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71123.png

Downloads & links

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Map

FileDownload / File: emd_71123.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 270.88 Å		0.85 Å/pix.
x 320 pix.
= 270.88 Å		0.85 Å/pix.
x 320 pix.
= 270.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8465 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.735
Minimum - Maximum-2.6835117 - 4.504663
Average (Standard dev.)0.00047211212 (±0.07890441)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 270.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_71123_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_71123_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : CD73 dimer bound to antibody Sym024

EntireName: CD73 dimer bound to antibody Sym024
Components
  • Complex: CD73 dimer bound to antibody Sym024

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Supramolecule #1: CD73 dimer bound to antibody Sym024

SupramoleculeName: CD73 dimer bound to antibody Sym024 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6
Source (natural)Organism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.5 mg/mL
BufferpH: 5.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS TITAN THEMIS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.66 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 286779
Initial angle assignmentType: COMMON LINE
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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