SUSHI DOMAINS OF IL-15RALFA AS SELECTIVE AND EFFECTIVE POTENTIATORS OF IL-15 ACTION THROUGH IL-15RBETA / GAMMA, IN THE HY15ERALON FUSION PROTEIN IL15RALFA SUSHI-IL 15.

摘要

Compound, to stimulate the IL-15Rbeta / gamma signaling pathway, to thereby induce and / or stimulate the activation and / or proliferation of IL-15Rbeta / gamma positive cells, such as NK cells and / or T lymphocytes , characterized in that it comprises at least one entity that binds to IL-15Rbeta / gamma, directly or indirectly linked by covalence to at least one polypeptide containing the sushi domain of the extracellular region of an IL-15Ralpha, wherein: - said at least one entity that binds IL-15Rbeta / gamma is IL-15, or is a fragment, a mimetic or an agonist of IL-15, wherein said fragment, mimetic or agonist of IL-15, has an affinity for binding to IL-15Rbeta / gamma that is not significantly inferior to that of a natural IL-15, and - the amino acid sequence of said at least one sushi-containing polypeptide: - is the amino acid sequence of the extracellular region of IL- 15Ralpha, or - is the amino acid sequence of a fragment of the e region x-cell IL-15Ralfa, wherein said fragment retains the sushi domain of said extracellular region of IL-15Ralfa, wherein said sushi domain is defined as the one that begins at the first cysteine residue encoded by exon 2 (C1), and terminates in the fourth cysteine residue encoded by exon 2 (C4), residues C1 and C4 being both included in said sushi domain, or - is a variant amino acid sequence having an identity of at least S5% with the sequence of amino acids of such extracellular region of IL-15Ralpha, or of such a fragment of the extracellular region of IL-15Ralpha, throughout the length of this amino acid sequence of the extracellular region or of the fragment of the extracellular region, with the proviso that each of the four cysteine residues (C1, C2, C3 and C4) of said sushi domain have been conserved in said variant sequence.