An IL-2-grafted antibody immunotherapy with potent efficacy against metastatic cancer

Dilara Sahin, Natalia Arenas-Ramirez, Matthias Rath, Ufuk Karakus, Monika Hümbelin, Merel Gogh, Lubor Borsig and Onur Boyman ()
Additional contact information
Dilara Sahin: University Hospital Zurich
Natalia Arenas-Ramirez: University Hospital Zurich
Matthias Rath: University Hospital Zurich
Ufuk Karakus: University Hospital Zurich
Monika Hümbelin: University Hospital Zurich
Merel Gogh: University of Zurich
Lubor Borsig: University of Zurich
Onur Boyman: University Hospital Zurich

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Modified interleukin-2 (IL-2) formulations are being tested in cancer patients. However, IL-2 immunotherapy damages IL-2 receptor (IL-2R)-positive endothelial cells and stimulates IL-2Rα (CD25)-expressing lymphocytes that curtail anti-tumor responses. A first generation of IL-2Rβ (CD122)-biased IL-2s addressed some of these drawbacks. Here, we present a second-generation CD122-biased IL-2, developed by splitting and permanently grafting unmutated human IL-2 (hIL-2) to its antigen-binding groove on the anti-hIL-2 monoclonal antibody NARA1, thereby generating NARA1leukin. In comparison to hIL-2/NARA1 complexes, NARA1leukin shows a longer in vivo half-life, completely avoids association with CD25, and more potently stimulates CD8+ T and natural killer cells. These effects result in strong anti-tumor responses in various pre-clinical cancer models, whereby NARA1leukin consistently surpasses the efficacy of hIL-2/NARA1 complexes in controlling metastatic disease. Collectively, NARA1leukin is a CD122-biased single-molecule construct based on unmutated hIL-2 with potent efficacy against advanced malignancies.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20220-1 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:11:y:2020:i:1:d:10.1038_s41467-020-20220-1

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

DOI: 10.1038/s41467-020-20220-1

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 ().