Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F22%3A00569602" target="_blank" >RIV/61388971:_____/22:00569602 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/22:00569602
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S2211124722013286?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124722013286?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.celrep.2022.111478" target="_blank" >10.1016/j.celrep.2022.111478</a>
Alternative languages
Result language
angličtina
Original language name
Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection
Original language description
Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over immune effector cells. Although promising, therapeutic translation of this approach is complicated by the need to optimize dosing ratios and by the instability of the cytokine/antibody complex. We leverage structural insights to engineer a single-chain hIL-2/F5111 antibody fusion protein, termed F5111 immunocytokine (IC), which potently and selectively activates and expands Tregs. F5111 IC confers protection in mouse models of colitis and checkpoint inhibitor-induced diabetes mellitus. These results provide a roadmap for IC design and establish a Treg-biased immunotherapy that could be clinically translated for autoimmune disease treatment.
Czech name
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Czech description
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Classification
Type
J<sub>SC</sub> - Article in a specialist periodical, which is included in the SCOPUS database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/GA20-13029S" target="_blank" >GA20-13029S: Novel clinically relevant IL-2 immunotherapeutics for cancer treatment</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Reports
ISSN
2211-1247
e-ISSN
2211-1247
Volume of the periodical
41
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
32
Pages from-to
111478
UT code for WoS article
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EID of the result in the Scopus database
2-s2.0-85140093956