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US 12,409,249 B2Granted
Compositions and methods for immune tolerance
AssigneesMassachusetts Institute of Technology, The General Hospital Corporation
InventorsSangeeta N. Bhatia, Arnav Chhabra, Marcela V. Maus
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Abstract
Immunotolerant engineered human tissue constructs are provided that are suitable for implantation into subjects. In some embodiments, the immunotolerance is controllable by an inducible system. Methods of making and using the immunotolerant engineered tissue constructs are provided.
Claims21
A composition suitable for implantation into a subject comprising:
- (a) a first cell population comprising parenchymal cells, endothelial cells, or a combination thereof, wherein the first cell population is allogenic to the subject and is not genetically engineered;
- and
- (b) a second cell population comprising stromal cells genetically engineered to express at least one immune checkpoint protein, which inhibit an immune response to the first cell population following implantation of the composition into the subject, wherein the at least one immune checkpoint protein is PD-L1, and wherein the stromal cells are not genetically engineered to express CTLA4.
An implantable graft for implantation into a subject comprising:
- (a) a first cell population comprising parenchymal cells, endothelial cells, or a combination thereof, wherein the first cell population is allogenic to the subject and is not genetically engineered;
- (b) a second cell population comprising stromal cells genetically engineered to express at least one immune checkpoint protein, which inhibit an immune response to the first cell population following implantation of the composition into the subject, wherein the at least one immune checkpoint protein is PD-L1, and wherein the stromal cells are not genetically engineered to express CTLA4, wherein the first and second cell populations are encapsulated in an extracellular matrix.
Dependencies are inferred from the claim text.