Anti-cd19 car t cells for treating b-cell malignancies and autoimmune diseases
OwnerHosein KOUROS-MEHR, Paul BRUNETTA +2inventors
InventorsHosein KOUROS-MEHR, Paul BRUNETTA, Diane Marie DAHILL, Alexandra BOWDEN
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Abstract
The present disclosure provides methods of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder by administering hypoimmune allogenic CD19-directed CAR T cells. Also disclosed are pharmaceutical compositions comprising hypoimmune allogenic CD19-directed CAR T cells, for use in treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder.
Claims34
A method of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder, the method comprising:
- administering to the subject a composition comprising a population of engineered hypoimmunogenic T cells, wherein the hypoimmunogenic T cells comprise one or more modifications that:
- (a) inactivate or disrupt one or more alleles of:
- (i) one or more major histocompatibility complex (MHC) class I molecules and/or one or more molecules that regulate expression of the one or more MHC class I molecules, (ii) one or more MHC class II molecules and/or one or more molecules that regulate expression of the one or more MHC class II molecules, and/or (iii) one or more T-cell receptor (TCR) molecules and/or one or more molecules that regulate expression of the one or more TCR molecules,
- (b) increase expression of CD47 encoded by a first exogenous polynucleotide,
- wherein the increased expression of (b) is relative to a control or wild-type T cell that does not comprise the modification, and
- (c) express a CD19-specific chimeric antigen receptor (CAR) encoded by a second exogenous polynucleotide.
A method of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder, the method comprising:
- administering to the subject a composition comprising a population of engineered hypoimmunogenic T cells comprising:
- (a) reduced expression of beta-2 microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), and T cell receptor alpha constant (TRAC) relative to a control or wild-type T cells,
- (b) increased expression of CD47 encoded by a first exogenous polynucleotide,
- wherein the increased expression of (b) is relative to the control or wild-type T cells, and
- (c) expression of a CD19-specific chimeric antigen receptor (CAR) encoded by a second exogenous polynucleotide.
An article of manufacture comprising a composition of a cell therapy, or one of a plurality of compositions of a cell therapy, comprising T cells expressing an anti-CD 19 chimeric antigen receptor (CAR), and instructions for administering the cell therapy, wherein the instructions specify administering the T cell composition according to the methods of any of claims 1-387.
A pharmaceutical composition comprising a population of engineered hypoimmunogenic T cells comprising:
- (a) reduced expression of beta-2-microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), and T cell receptor alpha constant (TRAC) relative to a control or wild-type T cells,
- (b) increased expression of CD47 encoded by a first exogenous polynucleotide relative to the control or wild-type T cells, and
- (c) expression of a CD19-specific chimeric antigen receptor (CAR) encoded by a second exogenous polynucleotide.
Dependencies are inferred from the claim text.