T cell receptor-deficient T cell compositions
AssigneeTrustees of Dartmouth College
InventorCharles L. Sentman
Life of this patent
Estimating the term…
Abstract
The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.
Claims23
An isolated modified primary human T cell, which is derived from a primary human T cell isolated from a human donor, that:
- (i) is modified to functionally impair or to reduce expression of the endogenous T cell receptor (TCR), and
- (ii) is further modified to express at least one functional exogenous non-TCR that comprises a chimeric receptor comprising a ligand binding domain attached to a signaling domain,
- wherein said modified primary human T cell is suitable for use in human therapy, and further wherein the isolated primary human T cell modified as in (i) and (ii) elicits no or a reduced graft-versus-host disease (GVHD) response in a histoincompatible human recipient as compared to the GVHD response elicited by a primary human T cell isolated from the same human donor that is only modified as in (ii).
An isolated modified primary human T cell, which is derived from a primary human T cell isolated from a human donor, that:
- (i) is modified to functionally impair or to reduce expression of the endogenous T cell receptor (TCR), and
- (ii) is further modified to express at least one functional exogenous non-TCR that comprises a chimeric receptor comprising a NKG2D ligand binding domain attached to a CD3 £ signaling domain,
- wherein said modified primary human T cell is suitable for use in human therapy, and further wherein the isolated primary human T cell modified as in (i) and (ii) elicits no or a reduced GVHD response in a histoincompatible human recipient as compared to the GVHD response elicited by a primary human T cell isolated from the same human donor that is only modified as in (ii).
Dependencies are inferred from the claim text.