US 2022/0177544 A1 · Interleukin-2 receptor (IL2R) and interleukin-2 (IL2) variants for specific activation of immune effector cells

Abstract

The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαβγ, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2Rα variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2Rαβγ, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

Claims85

Dependent claims

A system comprising:

(i) a receptor polypeptide comprising a mutein of the alpha subunit of interleukin-2 receptor (IL2R) or of a functional variant of the alpha subunit of IL2R, wherein the alpha subunit of IL2R or the functional variant thereof is substituted at at least one position,
(ii) a ligand polypeptide comprising a mutein of IL2 or of a functional variant of IL2, wherein the IL2 or the functional variant thereof is substituted at at least one position,
wherein the substitutions are such that
(a) the mutein under (ii) binds to and activates IL2R comprising the mutein under (i) as alpha subunit, and
(b) binding to and/or activation of IL2R comprising the mutein under (i) as alpha subunit by the mutein under (ii) exceeds binding to and/or activation of IL2R comprising the alpha subunit of IL2R or the functional variant thereof as alpha subunit by the mutein under (ii).

2 more elements

A system comprising:

(i) a receptor polypeptide comprising a mutein of the alpha subunit of interleukin-2 receptor (IL2R) or of a functional variant of the alpha subunit of IL2R, wherein the alpha subunit of IL2R or the functional variant thereof is substituted at at least a position having an acidic amino acid residue in wild type alpha subunit of IL2R that contacts a basic amino acid residue in wild type IL2 and/or is substituted at at least a position having a basic amino acid residue in wild type alpha subunit of IL2R that contacts an acidic amino acid residue in wild type IL2, wherein if the amino acid residue is an acidic amino acid residue in wild type alpha subunit of IL2R the substitution is by a basic amino acid residue and if the amino acid residue is a basic amino acid residue in wild type alpha subunit of IL2R the substitution is by an acidic amino acid residue,
(ii) a ligand polypeptide comprising a mutein of IL2 or of a functional variant of IL2, wherein when the alpha subunit of IL2R or the functional variant thereof is substituted at at least a position having an acidic amino acid residue in wild type alpha subunit of IL2R that contacts a basic amino acid residue in wild type IL2, the IL2 or the functional variant thereof is substituted at at least said basic amino acid residue in wild type IL2 and/or when the alpha subunit of IL2R or the functional variant thereof is substituted at at least a position having a basic amino acid residue in wild type alpha subunit of IL2R that contacts an acidic amino acid residue in wild type IL2, the IL2 or the functional variant thereof is substituted at at least said acidic amino acid residue in wild type IL2, wherein if the amino acid residue is a basic amino acid residue in wild type IL2 the substitution is by an acidic amino acid residue and if the amino acid residue is an acidic amino acid residue in wild type IL2 the substitution is by a basic amino acid residue.

Dependencies are inferred from the claim text.

Interleukin-2 receptor (IL2R) and interleukin-2 (IL2) variants for specific activation of immune effector cells

Life of this patent

Interleukin-2 receptor (IL2R) and interleukin-2 (IL2) variants for specific activation of immune effector cells

Life of this patent

Abstract

Claims85