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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<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>, 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. 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C.-D. and K.L. are employed at the Center of Molecular Immunology (CIM). CIM is the applicant of WO\/2018\/091003 (pending) covering a method for increasing the secretion levels of Interleukin-2 and proteins derived from it. G.R., T.C. and K.L. are the inventors. A.-P.-R. was also employed at CIM during this research. P.A.V., M.B., L.G. and S.D. declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"800"}}