Non-natural NKG2D receptors that do not directly signal the cells to which they are attached
AssigneeXyphos Biosciences Inc.
InventorsKaman C. Kim, David W. Martin, Jr., Steven Williams
Life of this patent
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Abstract
The present disclosure relates to non-natural NKG2D receptors attached to mammalian cell surfaces wherein the non-natural receptors do not directly signal or directly activate the cell when the receptor is bound by cognate non-natural α1-α2 domains of NKG2D ligands modified to specifically bind the non-natural NKG2D receptors. The non-natural α1-α2 domains of NKG2D ligands may be attached to heterologous atoms or molecules including polypeptides, in some embodiments cytokines or modified cytokines, antibodies or fragments of antibodies.
Claims4
A non-natural, modified NKG2D receptor comprising a human NKG2D ectodomain that comprises a substitution at position 152 selected from alanine, serine, threonine or valine and/or a substitution at residue 199 which is phenylalanine, wherein the receptor is attached to a mammalian cell, and wherein the receptor binds to non-natural, modified α1-α2 domains of NKG2D ligands but not to natural ligands of NKG2D, and wherein the modified NKG2D receptor does not comprise an active CD3-zeta intracellular signaling domain and does not activate intracellular signaling in the mammalian cell upon formation of an immunological synapse.
Dependencies are inferred from the claim text.