Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I24-Microfocus Macromolecular Crystallography	Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes Natalia Venetz-Arenas , Tim Schulte , Sandra Müller , Karin Wallden , Stefanie Fischer , Tom Resink , Nadir Kadri , Maria Paladino , Nicole Pina , Filip Radom , Denis Villemagne , Sandra Bruckmaier , Andreas Cornelius , Tanja Hospodarsch , Evren Alici , Hans-Gustaf Ljunggren , Benedict J. Chambers , Xiao Han , Renhua Sun , Marta Carroni , Victor Levitsky , Tatyana Sandalova , Marcel Walser , Adnane Achour Iscience DOI: 10.1016/j.isci.2025.113926 Diamond Proposal Number(s): [21625] Open Access Show Abstract ▼ Abstract: The balance between affinity and specificity in T cell receptor (TCR)-dependent targeting of HLA-restricted tumor-associated antigens presents a significant challenge for immunotherapy development. T cell engagers that circumvent these limitations are therefore of particular interest. We established a process to generate bispecific Designed Ankyrin Repeat Proteins (DARPins) that simultaneously target HLA-I/peptide complexes and CD3e. These high-affinity T cell engagers elicited CD8+ T cell activation against tumor targets with strong peptide specificity, as confirmed by X-scanning mutagenesis and functional killing assays. A cryo-EM structure of the ternary DARPin/HLA-A*0201/NY-ESO1157-165 complex revealed a rigid, concave DARPin surface spanning the full length of the peptide-binding cleft, contacting both α-helices and the peptide. The present findings reveal promising immuno-oncotherapeutic approaches and demonstrate the feasibility of rapidly developing DARPins with high affinity and specificity for HLA/peptide targets, which can be readily combined with a new generation of anti-CD3e-specific DARPins.	Nov 2025

Instruments / Technical Area

Publication Details

Published

Actions

I24-Microfocus Macromolecular Crystallography

Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes