Site-specific pegylated IL2 mutein with biased IL2 receptor binding for cancer immunotherapy.
Int Immunopharmacol
; 136: 112359, 2024 Jul 30.
Article
in En
| MEDLINE
| ID: mdl-38815348
ABSTRACT
While Interleukin 2 (IL2) has the capability to activate both NK and T cells robustly, its limited in vivo half-life, considerable toxicity, and tendency to boost Treg cells pose significant challenges, restricting its widespread application in cancer therapy. In this investigation, we engineered a novel IL2 variant (IL2-4M-PEG) with reduced CD25 binding activity and an extended half-life by substituting amino acids associated with CD25 binding and implementing site-directed PEGylation. IL2-4M-PEG notably amplifies effector cells over Treg cells. Furthermore, our findings reveal that IL2-4M-PEG, characterized by an extended half-life, exhibits anti-tumor effects in a mouse model. Consequently, this innovative IL2 holds the potential for enhancing combined cancer therapies in the future.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polyethylene Glycols
/
Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Immunotherapy
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: