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  Balancing the Nanoscale Organization in Multivalent Materials for Functional Inhibition of the Programmed Death-1 Immune Checkpoint

Paloja, K., Weiden, J., Hellmeier, J., Eklund, A. S., Reinhardt, S. C. M., Parish, I. A., et al. (2023). Balancing the Nanoscale Organization in Multivalent Materials for Functional Inhibition of the Programmed Death-1 Immune Checkpoint. ACS Nano, 18(2), 1381-1395. doi:10.1021/acsnano.3c06552.

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 Creators:
Paloja, Kaltrina, Author
Weiden, Jorieke, Author
Hellmeier, Joschka1, Author           
Eklund, Alexandra S.1, Author           
Reinhardt, Susanne C. M.1, Author           
Parish, Ian A., Author
Jungmann, Ralf1, Author           
Bastings, Maartje M. C., Author
Affiliations:
1Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149679              

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Free keywords: DNA-ORIGAMI; SUPERRESOLUTION MICROSCOPY; TOLERANCE; MOLECULE; AFFINITY; SYNAPSE; CANCER; CELLS; PD-1Chemistry; Science & Technology - Other Topics; Materials Science; spatial organization; dendritic cells; immunecheckpoint blockade; DNA origami; multivalency; PD-1; T cell activation;
 Abstract: Dendritic cells (DCs) regulate immune priming by expressing programmed death ligand 1 (PD-L1) and PD-L2, which interact with the inhibitory receptor PD-1 on activated T cells. PD-1 signaling regulates T cell effector functions and limits autoimmunity. Tumor cells can hijack this pathway by overexpressing PD-L1 to suppress antitumor T cell responses. Blocking this inhibitory pathway has been beneficial for the treatment of various cancer types, although only a subset of patients responds. A deepened understanding of the spatial organization and molecular interplay between PD-1 and its ligands may inform the design of more efficacious nanotherapeutics. We visualized the natural molecular PD-L1 organization on DCs by DNA-PAINT microscopy and created a template to engineer DNA-based nanoclusters presenting PD-1 at defined valencies, distances, and patterns. These multivalent nanomaterials were examined for their cellular binding and blocking ability. Our data show that PD-1 nano-organization has profound effects on ligand interaction and that the valency of PD-1 molecules modulates the effectiveness in restoring T cell function. This work highlights the power of spatially controlled functional materials to unravel the importance of multivalent patterns in the PD-1 pathway and presents alternative design strategies for immune-engineering.

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Language(s): eng - English
 Dates: 2023
 Publication Status: Issued
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 001144030800001
DOI: 10.1021/acsnano.3c06552
 Degree: -

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Title: ACS Nano
  Abbreviation : ACS Nano
Source Genre: Journal
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Publ. Info: Washington, DC : American Chemical Society
Pages: - Volume / Issue: 18 (2) Sequence Number: - Start / End Page: 1381 - 1395 Identifier: ISSN: 1936-0851
CoNE: https://pure.mpg.de/cone/journals/resource/1936-0851