Light-enhanced cytotoxicity and intracellular trafficking of the PD-L1-targeting photoimmunoconjugate EITC-atezolizumab
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10513891" target="_blank" >RIV/00216208:11160/25:10513891 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=8bznW3fKcK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=8bznW3fKcK</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2025.118550" target="_blank" >10.1016/j.biopha.2025.118550</a>
Alternative languages
Result language
angličtina
Original language name
Light-enhanced cytotoxicity and intracellular trafficking of the PD-L1-targeting photoimmunoconjugate EITC-atezolizumab
Original language description
Background: Photodynamic therapy (PDT) uses light to generate reactive oxygen species (ROS) that initiate cytotoxic responses in cancer cells. Photoimmunotherapy (PIT) improves PDT specificity by linking photosensitizers (PS) to monoclonal antibodies. A promising monoclonal antibody (mAb) for immunoconjugates is atezolizumab (Tecentriq), an EMA/FDA-approved PD-L1 immune checkpoint inhibitor for treating non-small cell lung cancer (NSCLC). Objective: Our goal was to: Optimize the cytotoxic efficacy of a photoimmunoconjugate of eosin-5-isothiocyanate and atezolizumab (EITC-atezolizumab) in NSCLC cells; Study the uptake and intracellular transport of atezolizumab; Evaluate EITC-atezolizumab as a candidate for photochemical internalization (PCI) of the ribosome-inactivating protein gelonin. Methods: Cytotoxic efficacy of EITC-atezolizumab was evaluated in NSCLC cell lines H1975 (PD-L1-high) and A549 (PD-L1-low) using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Confocal microscopy was employed to observe the uptake and intracellular localization of AlexaFluor647-atezolizumab and its colocalization with either LysoTracker(TM) Blue or an anti-CD63 antibody labelled with Alexa488. Results: EITC-atezolizumab PIT significantly enhanced cytotoxicity, showing much higher sensitivity in H1975 than A549 NSCLC cells. PIT with EITC-atezolizumab did not enhance gelonin efficacy. Confocal microscopy of H1975 cells revealed near-plasmamembrane puncta fluorescence of Alexa647-atezolizumab, with fractions clustering in CD63+ organelles peaking at 6 h. In A549 cells, AlexaFluor647-atezolizumab showed sustained accumulation in LysoTracker(TM) Blue+ vesicles for up to 24 h. Conclusion: To the best of our knowledge, this is the first documentation demonstrating that atezolizumab is transported to CD63-positive organelles, thereby enhancing our understanding of its intracellular trafficking. Our study also strengthens the concept of PIT and atezolizumab-based targeting of PD-L1+ NSCLCs.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biomedicine & Pharmacotherapy
ISSN
0753-3322
e-ISSN
1950-6007
Volume of the periodical
191
Issue of the periodical within the volume
October
Country of publishing house
FR - FRANCE
Number of pages
11
Pages from-to
118550
UT code for WoS article
999
EID of the result in the Scopus database
2-s2.0-105015598905