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US 2023/0265190 A1Published application
Alloreactive immune cell-distancing device and uses thereof for protecting donor-derived cells from allorejection
AssigneeMigal Galilee Research Institute Ltd.
InventorsGideon Gross, Hadas Weinstein-Marom
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Abstract
Provided herein are cell-distancing devices that protect cells that comprise them against host immune response when administered in a host. The disclosed cell-distancing devices engage with host immune cells and reduce their activity against cells that comprise the devices. Compositions of cell-distancing devices, cells comprising cell-distancing devices, and method of making and using such compositions are disclosed herein.
Claims29
An alloreactive T cell-distancing device comprising:
- (a) an extracellular membrane-distal domain comprising a binding domain capable of binding a member of a central supramolecular activation cluster (SMAC) of the immunological synapse or a member closely associated therewith;
- (b) an extracellular elongation domain comprising at least one rigid protein module;
- (c) a transmembrane domain;
- and optionally
- (d) an extracellular membrane-proximal domain, optionally less than 5 nm in length and/or lacking a glycosylphosphatidylinositol (GPI) anchor;
- and/or
- (e) an intracellular domain optionally capable of associating, or co-clustering with, MHC molecules,
- wherein (a)-(c) are connected from N-terminus to C-terminus in the following order via one or more hinges:
- transmembrane domain, extracellular elongation domain, and extracellular membrane-distal domain;
- intracellular domain, transmembrane domain, extracellular elongation domain, and extracellular membrane-distal domain;
- or intracellular domain, transmembrane domain, extracellular membrane-proximal domain, extracellular elongation domain, and extracellular membrane-distal domain.
8 more elements
Dependencies are inferred from the claim text.