Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F24%3A00598961" target="_blank" >RIV/61388971:_____/24:00598961 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/24:00598961 RIV/00216208:11310/24:10493822
Result on the web
<a href="https://insight.jci.org/articles/view/173469/pdf" target="_blank" >https://insight.jci.org/articles/view/173469/pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1172/jci.insight.173469" target="_blank" >10.1172/jci.insight.173469</a>
Alternative languages
Result language
angličtina
Original language name
Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity
Original language description
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of both proinflammatory immune effector cells and antiinflammatory regulatory T cells, toxicity at high doses, and short serum halflife. One approach to improve the selectivity, safety, and longevity of IL-2 is complexing with anti-IL-2 antibodies that bias the cytokine toward immune effector cell activation. Although this strategy shows potential in preclinical models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multiprotein drug and concerns regarding complex stability. Here, we introduced a versatile approach to designing intramolecularly assembled singleagent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine toward immune effector cells. We optimized IC construction and engineered the cytokine/antibody affinity to improve immune bias. We demonstrated that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared with natural IL-2, both alone and combined with immune checkpoint inhibitors. Moreover, therapeutic efficacy was observed without inducing toxicity. This work presents a roadmap for the design and translation of cytokine/antibody fusion proteins.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science 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
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JCI Insight
ISSN
2379-3708
e-ISSN
2379-3708
Volume of the periodical
9
Issue of the periodical within the volume
18
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
e173469
UT code for WoS article
001320153900001
EID of the result in the Scopus database
2-s2.0-85204820066