Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00586357" target="_blank" >RIV/61388963:_____/24:00586357 - isvavai.cz</a>

Alternative codes found

RIV/61389013:_____/24:00586357 RIV/00216208:11310/24:10492338

Result on the web

<a href="https://doi.org/10.1016/j.jbc.2024.107325" target="_blank" >https://doi.org/10.1016/j.jbc.2024.107325</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2024.107325" target="_blank" >10.1016/j.jbc.2024.107325</a>

Result language

angličtina

Original language name

Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker

Original language description

Immune checkpoint blockade (ICB) using monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) is the treatment of choice for cancer immunotherapy. However, low tissue permeability, immunogenicity, immune-related adverse effects, and high cost could be possibly improved using alternative approaches. On the other hand, synthetic low-molecular-weight (LMW) PD-1/PD-L1 blockers have failed to progress beyond invitro studies, mostly due to low binding affinity or poor pharmacological characteristics resulting from their limited solubility and/or stability. Here, we report the development of polymer-based anti-human PD-L1 antibody mimetics (alpha-hPD-L1 iBodies) by attaching the macrocyclic peptide WL12 to a N-(2-hydroxypropyl)methacrylamide copolymer. We characterized the binding properties of iBodies using surface plasmon resonance, enzyme-linked immunosorbent assay, flow cytometry, confocal microscopy, and a cellular ICB model. We found that the alpha-hPD-L1 iBodies specifically target human PD-L1 (hPD-L1) and block the PD-1/PD-L1 interaction invitro, comparable to the atezolizumab, durvalumab, and avelumab licensed monoclonal antibodies targeting PD-L1. Our findings suggest that iBodies can be used as experimental tools to target hPD-L1 and could serve as a platform to potentiate the therapeutic effect of hPD-L1-targeting small molecules by improving their affinity and pharmacokinetic properties.

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

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Volume of the periodical

300

Issue of the periodical within the volume

6

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

13

Pages from-to

107325

UT code for WoS article

001345352100001

EID of the result in the Scopus database

2-s2.0-85194036777