Xyphos Biosciences Inc.

The J. David Gladstone Institutes

Kaman C Kim

David W Martin, Jr

Warner C Greene

Steven R Williams

Kyle Landgraf

Nigel Killeen

Eytan Herzig

Kyle E Landgraf

This present disclosure relates generally to the production of polypeptides comprised of modified α1-α2 domains of NKG2D ligands which bind specifically to a non-natural ectodomain of a non-natural NKG2D receptor and wherein heterologous molecules are attached to the modified α1-α2 domains of NKG2D ligands. The present disclosure further relates to modified α1-α2 domains of NKG2D ligands attached to heterologous molecules including polypeptides, and in some embodiments, antibodies or fragments of antibodies. The present disclosure also relates to modified forms of the NKG2D receptor engineered to provide a combination of enhanced and diminished binding to non-natural and natural versions of NKG2D ligands, respectively.

Modified A1-A2 domains of non-natural NKG2D ligands that bind non-natural NKG2D receptors

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.

Non-natural NKG2D receptors that do not directly signal the cells to which they are attached

This application relates generally to the production of modified, non-natural &#x3b1;1-&#x3b1;2 domains of NKG2D ligands with attached polypeptides having specific target-binding properties, for example, antibodies or variable fragments of antibodies, that are selectively delivered to Chimeric Antigen Receptors (CARs) comprised of modified, non-natural NKG2D receptors on engineered mammalian cells. The targeting of surface-expressed molecules includes those of virus-infected cells that can then be attacked and ablated by engineered cells of the immunity system expressing CARs cognate to the modified, non-natural &#x3b1;1-&#x3b1;2 domains of NKG2D ligands with attached polypeptides.

Modified non-natural NKG2D ligands that selectively deliver attached heterologous molecules to non-natural NKG2D receptors on car-cells

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San Bruno, CA, United States of America

Kaman C Kim