---
title: 論文紹介: Proximity-guided graph learning reveals tumour-associated proximity antigens
tags:  #interactome #proteomics  
author: [Shunichi Ito](https://docswell.com/user/shunichi1100921)
site: [Docswell](https://www.docswell.com/)
thumbnail: https://bcdn.docswell.com/page/LJL894QPER.jpg?width=480
description: 近接性ラベリング技術とGNNによって、がん関連近接抗原 (TAPA) を同定し、ADCやTCEなどの治療方法で実際に検証した論文です。
published: November 02, 26
canonical: https://docswell.com/s/shunichi1100921/5Y8J74-proximity-guided-graph-learning
---
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Nature | Vol 658 | 09 September 2026
Proximity-guided graph learning reveals
tumour-associated proximity antigens
Cody Scandore, Clare F. Malone, Christopher K. May et al.
Corresponding authors: Rob C. Oslund and Olugbeminiyi O. Fadeyi
InduPro, Cambridge, Massachusetts · Seattle, Washington, USA
2026.11.02 Full | Shunichi Ito


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Proximity reveals therapeutic co-targets
Fig. 1
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A nearby antigen can refine tumour targeting
Local membrane neighbourhoods
TAA: tumour-associated antigen
Fig. 1, enlarged details
TAA + nearby TAPA
TAPA: tumour-associated proximity antigen
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The photocatalyst labels only nearby proteins
Ir/Dz
Short-lived carbene
≤ 5 ns
RFT/BT
Longer-lived radical
~0.1 ms
Fig. 2a
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Spatial specificity is fixed before lysis
248 micromaps: 12 RTKs across 28 tumour cell systems
Streptavidin enrichment, LysC/trypsin digestion, TMTpro, SPS-MS3
Fig. 2a
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Proximity mapping reveals unexplored RTK pairs
Novel proximal pairs: EGFR–PTK7, MET–EPHB2, HER3–MST1R
Only EGFR×MET, EGFR×HER3 and HER2×HER3 are clinically explored
Fig. 2b,c
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MetaMap infers neighbours from shared enrichment
Spearman correlation across 248 micromaps
Fig. 3a,b
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MetaMap extends a known integrin community
2.7–6.5× over random protein pairs
FAP, CD81, RECK and PAPPA join the integrin core without prior annotation
Fig. 3d,e
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Three models predict which proteins are associated
Proximity enrichment
Protein expression
Protein association
DIA measurement
Reported Network (STRING)
Graph Neural Network
database of protein associations
Three kinds
of GNN
Fig. 4b
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Proximity adds predictive value beyond abundance
Fig. 4c, GAT feature ablation
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CDCP1 emerges as an EGFR-associated co-target
MetaMap support
Model-prioritized EGFR partners: HER2, HER3, MET and the non-RTK CDCP1
Fig. 4d,e
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EGFR–CDCP1 proximity depends on cell context
Surface expression
Fig. 4f,g
EGFR-anchored enrichment
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EGFR–CDCP1 proximity persists across tumour contexts
Fig. 4h
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Dual engagement increases antibody internalization
Unconjugated antibody
Uptake is much lower in primary epithelial cells
Fig. 5a,b. Representative SW48 result
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The bispecific ADC increases tumour-cell killing
vcMMAE payload, Drug / Ab (DAR) = 2
SW48 IC50: 11.4 nM
Primary epithelial cells: 324–947 nM
Fig. 5c. Primary-cell IC50: Supplementary Fig. 28c
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The bispecific ADC improves control at a lower dose
1 mg/kg: complete TGI versus 43% with EGFR-only ADC
Fig. 5d,e. SW48 xenografts, n = 8 mice per group
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Coordinated targeting outperforms separate ADCs
Fig. 5f,g. SW900 xenografts, n = 9 mice per group
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The same target pair improves T-cell-directed killing
Trispecific TCE: T-cell engagement
Fig. 5h,i. In vitro T-cell-dependent cytotoxicity
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Limitation of proximity mapping
Local labelling does not
resolve direct binding
Avidity and trafficking also
influence efficacy
Proximity maps rest on
technical triplicates only
Tumour and normal tissues
from the same patient
remain essential
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Surface proteomics can prioritize spatial co-targets
Measure local neighbourhoods
Prioritize TAA–TAPA pairs
Validate therapeutic co-engagement
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Appendix


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Primary epithelial cells show lower uptake and killing
Supplementary Fig. 28b,c
B1


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CDCP1 depletion reduces bispecific ADC activity
TGI: 97% in parental tumours, 46% after CDCP1 knockdown
Extended Data Fig. 2c,d. SW48 dual-flank study
B2


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MAD normalization makes micromaps comparable
Supplementary Fig. 9. Methods
B3


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Graph construction and model architectures
Fig. 4a. Supplementary Notes 1 and 2
B4


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Reciprocal anchoring reproduces the EGFR–CDCP1 pair
Reciprocal anchoring
Monovalent direct conjugates
Both directions, both chemistries, a different epitope, no secondary antibody
Extended Data Fig. 1b,d
B5


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Both chemistries recover every intended target
Target enriched in 248 of 248 maps
Supplementary Fig. 8
Across chemistries: r = 0.679, bias −0.55 log2FC
B6


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Enrichment is independent of proteomic abundance
Supplementary Fig. 13
Supplementary Fig. 14
B7


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GAT results are consistent with DepMap
Supplementary Fig. 18
B8


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NanoBiT experiments also validated that bispecific
antibody capture both EGFR and CDCP1
Supplementary Fig. 27
B9


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Reciprocal EGFR-CDCP1 enrichment is reproduced across
micromapping formats, binders and cell systems.
Extended Data Fig. 1
B10


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TMTpro-SPS-MS3 resolves chimera spectra
Step 1: TMTpro labeling
Step 3: Select fragment ion
MS2
Synchronous precursor selection (SPS)
Step 2: Select precursor ion
Step 4: Quantitate reporter ion
MS1
MS3
B11