Myomedin variants developed for in vitro PD-L1 diagnostics in tissue samples of non-small cell lung carcinoma patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00636827" target="_blank" >RIV/86652036:_____/25:00636827 - isvavai.cz</a>

Alternative codes found

RIV/61988987:17110/25:A2603CKN RIV/61989592:15110/25:73633185 RIV/00843989:_____/25:E0111735

Result on the web

<a href="https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06699-6" target="_blank" >https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06699-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12967-025-06699-6" target="_blank" >10.1186/s12967-025-06699-6</a>

Result language

angličtina

Original language name

Myomedin variants developed for in vitro PD-L1 diagnostics in tissue samples of non-small cell lung carcinoma patients

Original language description

BackgroundThe treatment of non-small cell lung cancer (NSCLC) patients is correlated with the efficacy of immune checkpoint blockade therapy (ICB) targeting programmed cell death ligand 1 (PD-L1) or its cognate receptor (PD-1) on cancer cells or infiltrating immune cells. Analysis of PD-L1/PD-1 expression in tumor tissue represents a crucial step before PD-L1/PD-1 blocker usage.MethodsWe used directed evolution of protein variants derived from a 13 kDa Myomedin loop-type combinatorial library with 12 randomized amino acid residues to select high-affinity binders of human PD-L1 (hPD-L1). After the ribosome display, individual clones were screened by ELISA. Detailed analysis of binding affinity and kinetics was performed using LigandTracer. The specificity of Myomedins was assessed using fluorescent microscopy on HEK293T-transfected cells and cultured cancer cells in vitro, formalin-fixed paraffin-embedded (FFPE) sections of human tonsils, and FFPE tumor samples of NSCLC patients.ResultsSeven identified PD-L1 binders, called MLE, showed positive staining for hPD-L1 on transfected HEK293T cells and cultured MCF-7 cells. MLE031, MLE105, MLE249, and MLE309 exhibited high affinity to both human and mouse PD-L1-transfected HEK293T cells measured with LigandTracer. The diagnostic potential of MLE variants was tested on human tonsillitis tissue and compared with diagnostic anti-PD-L1 antibody DAKO 28-8 and PD-L1 IHC 22C3 pharmDx antibody. MLE249 and MLE309 exhibited an excellent overlap with diagnostic DAKO 28-8 (Pearson<acute accent>s coefficient (r) = 0.836 and 0.731, respectively) on human tonsils on which MLE309 exhibited also excellent overlap with diagnostic 22C3 antibody (r = 0.876). Using three NSCLC tissues, MLE249 staining overlaps with 28-8 antibody (r = 0.455-0.883), and MLE309 exhibited overlap with 22C3 antibody (r = 0.534-0.619). Three MLE proteins fused with Fc fragments of rabbit IgG, MLE249-rFc, MLE309-rFc and MLE031-rFc, exhibited very good overlap with anti-PD-L1 antibody 28-8 on tonsil tissue (r = 0.691, 0.610, and 0.667, respectively). Finally, MLE249-rFc, MLE309-rFc and MLE031-rFc exhibited higher sensitivity in comparison to IHC 22C3 antibody using routine immunohistochemistry staining system Ventana, which is one of gold standards for PD-L1 diagnosis.ConclusionsWe demonstrated the development of MLE Myomedins specifically recognizing hPD-L1 that may serve as a refinement tool for clinical PD-L1 detection.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NU21-03-00372" target="_blank" >NU21-03-00372: Small binding proteins targeting PD-1/PD-L1 immune checkpoint proteins as new diagnostic tools</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Translational Medicine

ISSN

1479-5876

e-ISSN

1479-5876

Volume of the periodical

23

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

19

Pages from-to

655

UT code for WoS article

001508608700004

EID of the result in the Scopus database

2-s2.0-105007883391