Modified effector cell (or chimeric receptor) for treating disialoganglioside GD2-expressing neoplasia
AssigneeSt. Jude Children's Research Hospital
InventorsMassimo Dominici, Sara Caldrer, Maria Carlotta Spano, Paolo Paolucci, Marco Bestagno, Dario Campana
Life of this patent
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Abstract
A modified effector cell includes a non-reversibly produced vector-encoded anti-GD2-BB-ζ chimeric receptor for use in disialoganglioside GD2-expressing neoplasia, which is inserted in the cell, to obtain an effector cell that stably produces the anti-GD2-BB-ζ chimeric receptor, the chimeric receptor having two distinct mutually fused portions, i.e. an intra-cytoplasmic portion and an extra-cytoplasmic portion.
Claims8
A modified effector cell for treating disialoganglioside GD2-expressing neoplasia, comprising:
- a cytoplasm with a nucleus therein, the cytoplasm being enclosed in a membrane;
- and
- a chimeric receptor, wherein the chimeric receptor comprises an extracytoplasmic portion, a transmembrane portion, and an intracytoplasmic portion,
- wherein the extracytoplasmic portion comprises, in order:
- a signal peptide containing an intron sequence,
- a first sequence encoding for a variable region of a light chain of the anti-GD2 immunoglobulin M (IgM) antibody,
- a linker that allows folding of a GD2 antigen recognition region of an anti-GD2 IgM antibody, and
- a second sequence encoding for a variable region of a heavy chain of the anti-GD2 IgM antibody, and
- wherein the transmembrane portion and the intracytoplasmic portion comprise, in order:
- a hinge and transmembrane domain of a human lymphocyte CD8α molecule,
- an intracellular portion of a 4-1BB co-stimulatory molecule, and
- an intracellular portion of a human lymphocyte CD3-ζ molecule.
A polyclonal mixture of effector cells for treating disialoganglioside GD2-expressing neoplasia, comprising:
- a plurality of modified effector cells comprising:
- a cytoplasm with a nucleus therein, the cytoplasm being enclosed in a membrane;
- and
- a chimeric receptor, wherein the chimeric receptor comprises an extracytoplasmic portion, a transmembrane portion, and an intracytoplasmic portion,
- wherein the extracytoplasmic portion comprises, in order:
- a signal peptide containing an intron sequence,
- a first sequence encoding for a variable region of a light chain of the anti-GD2 immunoglobulin M (IgM) antibody,
- a linker that allows folding of a GD2 antigen recognition region of an anti-GD2 IgM antibody, and
- a second sequence encoding for a variable region of a heavy chain of the anti-GD2 IgM antibody,
- wherein the transmembrane portion and the intracytoplasmic portion comprise, in order:
- a hinge and transmembrane domain of a human lymphocyte CD8α molecule,
- an intracellular portion of a 4-1BB co-stimulatory molecule, and
- an intracellular portion of a human lymphocyte CD3-ζ molecule, and
- wherein at least 20% of the modified effector cells comprises a CD3+/CD8+/CD56+ phenotype.
Dependencies are inferred from the claim text.