Dendritic cell progenitors engineered to express extracellular-vesicle–internalizing receptors enhance cancer immunotherapy in mouse models

Ali Ghasemi, Amaia Martinez-Usatorre, Yang Liu, Hadrien Demagny, Luqing Li, Yahya Mohammadzadeh, Andreas Hurtado, Mehdi Hicham, Linda Henneman, Colin E. J. Pritchard, Daniel E. Speiser, Denis Migliorini and Michele De Palma ()
Additional contact information
Ali Ghasemi: Swiss Federal Institute of Technology in Lausanne (EPFL)
Amaia Martinez-Usatorre: Swiss Federal Institute of Technology in Lausanne (EPFL)
Yang Liu: Swiss Federal Institute of Technology in Lausanne (EPFL)
Hadrien Demagny: EPFL
Luqing Li: Swiss Federal Institute of Technology in Lausanne (EPFL)
Yahya Mohammadzadeh: Swiss Federal Institute of Technology in Lausanne (EPFL)
Andreas Hurtado: Swiss Federal Institute of Technology in Lausanne (EPFL)
Mehdi Hicham: Swiss Federal Institute of Technology in Lausanne (EPFL)
Linda Henneman: Netherlands Cancer Institute (NKI)
Colin E. J. Pritchard: Netherlands Cancer Institute (NKI)
Daniel E. Speiser: University of Lausanne (UNIL)
Denis Migliorini: Agora Cancer Research Center
Michele De Palma: Swiss Federal Institute of Technology in Lausanne (EPFL)

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Cancer immunotherapy using dendritic cells (DC) pulsed ex vivo with tumour antigens is considered safe, but its clinical efficacy is generally modest. Here we engineer DC progenitors (DCP), which can replenish conventional type 1 DCs (cDC1) in mice, to constitutively express IL-12 together with a non-signalling chimeric receptor, termed extracellular vesicle-internalizing receptor (EVIR). By binding to a bait molecule (GD2 disialoganglioside) expressed on cancer cells and their EVs, the EVIR enforces EV internalization by cDC1 to promote their cross-dressing with preformed, tumour-derived MHCI-peptide complexes. Upon systemic deployment to mice, the engineered DCPs cause only mild and transient elevation of liver enzymes, acquire tumour-derived material, engage tumour-specific T cells, and enhance the efficacy of PD-1 blockade in an immunotherapy-resistant melanoma model comprising both GD2-positive and -negative cancer cells, without the need for ex vivo antigen pulsing. These results indicate that EVIR-engineered DCPs may avert the positive selection of antigen-negative cancer cells, potentially addressing a critical limitation of immunotherapies targeting defined tumour antigens.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64172-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64172-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64172-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().