Delivery of multi-cytokine signals by overexpression of wild-type or mutant signal transduction molecules
AssigneeThe Trustees of the University of Pennsylvania
InventorSaar GILL
Life of this patent
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Abstract
The present disclosure provides methods for delivering multi-cytokine signals by overexpressing wild-type or mutant signal transduction molecules in lymphocytes (e.g. CAR T cells). Compositions and methods of treatment are also provided.
Claims46
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK2, wherein the JAK2 comprises a valine to phenylalanine substitution at codon 617 (JAK2V617F).
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK2, wherein the JAK2 comprises a valine to phenylalanine substitution at codon 617 (JAK2V617F).
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK3, wherein the JAK3 comprises a methionine to isoleucine substitution at codon 511 (JAK3M511I).
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK3, wherein the JAK3 comprises a methionine to isoleucine substitution at codon 511 (JAK3M511I).
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising
- a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular domain, and
- a chimeric receptor comprising Granulocyte Colony Stimulating Factor Receptor (G-CSFR), Interleukin-2 Receptor Beta (IL2Rβ), and Interleukin-2 Receptor Gamma (IL2Ry).
A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a modified immune cell or precursor cell thereof comprising
- a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular domain, and
- a chimeric receptor comprising Granulocyte Colony Stimulating Factor Receptor (G-CSFR), Interleukin-2 Receptor Beta (IL2Rβ), and Interleukin-2 Receptor Gamma (IL2Ry).
The method of any preceding claim, further comprising administering a cytokine to the subject.
The method of any preceding claim, further comprising administering a JAK1/2 inhibitor.
The method of any preceding claim, wherein the cell is a T cell.
The method of any preceding claim, wherein the cell is an autologous cell.
The method of any preceding claim, wherein the disease or disorder is cancer.
A modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK2, wherein the JAK2 comprises a valine to phenylalanine substitution at codon 617 (JAK2V617F).
A modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK2, wherein the JAK2 comprises a valine to phenylalanine substitution at codon 617 (JAK2V617F).
A modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK3, wherein the JAK3 comprises a methionine to isoleucine substitution at codon 511 (JAK3M511I).
A modified immune cell or precursor cell thereof comprising a chimeric antigen receptor (CAR) and an overexpressed JAK3, wherein the JAK3 comprises a methionine to isoleucine substitution at codon 511 (JAK3M51II).
A modified immune cell or precursor cell thereof comprising
- a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular domain, and
- a chimeric receptor comprising G-CSFR, IL2Rβ, and IL2Ry.
A modified immune cell or precursor cell thereof comprising
- a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular domain, and
- a chimeric receptor comprising G-CSFR, IL2Rβ, and IL2Ry.
The modified immune cell or precursor cell thereof of any preceding claim, wherein the cell is a T cell.
The modified immune cell or precursor cell thereof of any preceding claim, wherein the cell is an autologous cell.
The modified immune cell or precursor cell of any preceding claim, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and an overexpressed JAK2V617F.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and an overexpressed JAK2V617F.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and an overexpressed JAK3M511I.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and an overexpressed JAK3M511I.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and a chimeric receptor comprising G-CSFR, IL2Rβ, and IL2Rγ.
A method of expanding CAR T cells in a subject, the method comprising administering to the subject a modified T cell comprising a CAR and a chimeric receptor comprising G-CSFR, IL2Rβ, and IL2Ry.
Dependencies are inferred from the claim text.