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US 12,698,499 B2Granted
Identifying epigenetic and transcriptional targets to prevent and reverse T cell exhaustion
AssigneeThe Trustees of the University of Pennsylvania
InventorsE. John Wherry, Omar Khan, Martha Jordan
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Abstract
The present invention provides methods of preventing, reversing or increasing T cell exhaustion in a patient having a disease. The present invention also provides methods for treating a disease in a patient having the disease. The present invention also provides an engineered T cell comprising a high priority epigenetic pathway that has been targeted, and uses thereof.
Claims9
A method of making an improved cell therapy composition, comprising the steps of:
- (a) obtaining a sample comprising lymphocytes from a subject;
- (b) reducing or eliminating expression of one or more genes required for the induction and/or maintenance of exhausted CD8+ T lymphocytes (TEX) in the lymphocytes;
- and
- (c) engineering the lymphocytes to target a therapeutically relevant antigen;
- wherein the one or more genes required for the induction and/or maintenance of TEX is a transcription factor or a gene involved in epigenetic modification of DNA;
- and
- wherein the transcription factor is TOX.
4 more elements
A method of reducing or preventing T cell exhaustion in a lymphocyte obtained from a subject, comprising the steps of:
- reducing or eliminating expression of one or more genes required for the induction and/or maintenance of exhausted CD8+ T lymphocytes (TEX) in the lymphocyte;
- wherein the gene required for induction and/or maintenance of exhausted CD8+ T lymphocytes is TOX;
- and
- wherein the lymphocyte is a CD8+ T cell.
1 more element
Dependencies are inferred from the claim text.