Evidence map›Paper›PMID 42624861›Full record

ArticleNature communications2026

AI-enabled discovery and biochemical optimization of minibinders targeting cancer cell-surface proteins.

Bianca Broske, Benjamin A McEnroe, Sophie C Frechen, Tim N Kempchen, Caroline I Fandrey, Elisabeth Tan, Dominic Ferber, Michelle C R Yong, Marie Kleinert, Julia M Messmer and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Bianca Broske *Institute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-3898-436X
Benjamin A McEnroe *Institute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0009-7574-565X
Sophie C Frechen *Institute of Structural Biology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0004-5573-1131
Tim N Kempchen *Institute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0007-0173-2026
Caroline I Fandrey *Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Elisabeth TanInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0003-1787-496X
Dominic FerberInstitute of Structural Biology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-2633-2858
Michelle C R YongInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Marie KleinertInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Julia M MessmerInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Peter KonopkaInstitute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Alexander HochInstitute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-4790-5507
Katja BlumenstockInstitute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Jan M P TödtmannCore Facility Nanobodies, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-9104-5858
Johannes OldenburgInstitute for Experimental Hematology and Transfusion Medicine, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-1585-4100
Heiko RühlInstitute for Experimental Hematology and Transfusion Medicine, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-0672-2453
Alexander SemaanDepartment of Surgery, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0001-5424-3217
Marieta I TomaInstitute for Pathology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Kristina MarkovaInstitute for Molecular Medicine and Experimental Immunology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Sebastian KoboldInstitute of Clinical Pharmacology, LMU University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-5612-4673
Tim RollenskeInstitute for Molecular Medicine and Experimental Immunology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-1982-3253
Matthias GeyerInstitute of Structural Biology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-7718-5002
Stephan MenzelCore Facility Nanobodies, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0009-0005-4742-9335
Tobias BaldInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-0061-235X
Jonathan L Schmid-BurgkInstitute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, University Hospital Bonn, Bonn, Germany.
Gregor HageluekenInstitute of Structural Biology, University of Bonn, University Hospital Bonn, Bonn, Germany. michael.hoelzel@ukbonn.de.ORCID http://orcid.org/0000-0001-8781-5664
Michael HölzelInstitute for Experimental Oncology, University of Bonn, University Hospital Bonn, Bonn, Germany. hagelueken@uni-bonn.de.ORCID http://orcid.org/0000-0003-4048-8824

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) EXC2151 - project ID 390873048Melanoma Research Alliance (MRA) 409510
6 · The paper itself

Abstract

Experimental validation and functional optimization remain bottlenecks in AI-based protein design. We present a scalable workflow for developing AI-designed minibinders against cancer-associated surface proteins. Screening thousands of designs using mammalian cell-surface display identifies several high-affinity PD-L1 minibinders but far fewer for CD276 (B7-H3) and VTCN1 (B7-H4), highlighting substantial target dependence. Interface predicted template modeling (ipTM) scores generated by Chai-1 with ESM embeddings correlate with binding success and capture deleterious effects of interface mutations. Fluorophore-labeled AI-minibinders enable flow-cytometric staining comparable to conventional antibodies. However, when incorporated into chimeric antigen receptors (CAR), some show poor cell-surface trafficking and limited functionality. Redesign through a genetic algorithm-based diversification strategy that preserves the binding interface while changing non-binding surfaces experimentally reveals an isoelectric point (pI) window that improves CAR expression and enhances target-selective tumor cell killing. Our findings identify biochemical optimization beyond the binding interface as a critical requirement for translating AI-minibinders into functional applications.

Indexed as

Membrane ProteinsNeoplasmsProtein EngineeringAlgorithmsAnimalsCell Line, TumorHumansProtein BindingReceptors, Chimeric AntigenMembrane ProteinsReceptors, Chimeric Antigen

Identifiers

PMID42624861
PMCPMC13494018

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.