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- Title
Directed evolution of super-secreted variants from phage-displayed human Interleukin-2.
- Authors
Rojas, Gertrudis; Carmenate, Tania; Santo-Tomás, Julio Felipe; Valiente, Pedro A.; Becker, Marlies; Pérez-Riverón, Annia; Tundidor, Yaima; Ortiz, Yaquelín; Fernandez de Cossio-Diaz, Jorge; Graça, Luis; Dübel, Stefan; León, Kalet
- Abstract
Selection from a phage display library derived from human Interleukin-2 (IL-2) yielded mutated variants with greatly enhanced display levels of the functional cytokine on filamentous phages. Introduction of a single amino acid replacement selected that way (K35E) increased the secretion levels of IL-2-containing fusion proteins from human transfected host cells up to 20-fold. Super-secreted (K35E) IL-2/Fc is biologically active in vitro and in vivo, has anti-tumor activity and exhibits a remarkable reduction in its aggregation propensity- the major manufacturability issue limiting IL-2 usefulness up to now. Improvement of secretion was also shown for a panel of IL-2-engineered variants with altered receptor binding properties, including a selective agonist and a super agonist that kept their unique properties. Our findings will improve developability of the growing family of IL-2-derived immunotherapeutic agents and could have a broader impact on the engineering of structurally related four-alpha-helix bundle cytokines.
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-018-37280-5