Removal of endogenous tcr chains for enhanced tcr-based immunotherapies
AssigneeThe Trustees of Columbia University in the City of New York
InventorsMohsen Khosravi MAHARLOOEI, Giorgia ZANETTI, Remi CREUSOT, Megan SYKES
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Abstract
Methods and compositions for treating a disease in a subject comprising administering an adoptive cell therapy (ACT) to the subject, the ACT comprising delivering a modified lymphocyte comprising a modified T cell receptor (TCR) or a chimeric antigen receptor (CAR); at least one inactivated endogenous TCRα chain allele; and at least one inactivated endogenous TCRβ chain allele.
Claims20
A method of treating a disease in a subject comprising administering an adoptive cell therapy (ACT) to the subject, the ACT comprising delivering a modified lymphocyte comprising
- i) a modified T cell receptor (TCR) or a chimeric antigen receptor (CAR);
- ii) at least one inactivated endogenous TCRα chain allele;
- and
- iii) at least one inactivated endogenous TCRβ chain allele;
- thereby treating the disease of the subject.
A method of modifying a cell for adoptive cell therapy, the method comprising:
- inactivating an endogenous TCRα chain allele and an endogenous TCRβ chain allele encoded by the cell, preferably by introducing at least one engineered nuclease to the cell,
- thereby modifying the cell for adoptive cell therapy.
A mammalian immune cell modified by having a modified T cell receptor (TCR) or a chimeric antigen receptor (CAR);
- at least one inactivated endogenous TCRα chain allele;
- and at least one inactivated endogenous TCRβ chain allele.
Dependencies are inferred from the claim text.