IP Library › Granted Patent US 12,680,076
Granted Patent B2
US 12,680,076 · App. 18/056,544 · Granted Jul 14, 2026

Methods for engineering allogeneic and highly active T cell for immunotheraphy

Inventors: Roman Galetto (Paris, FR); Agnes Gouble (Paris, FR); Stephanie Grosse (Saint Cyr sur Morin, FR); Cécile Schiffer-Mannioui (Villiers sur Marne, FR); Laurent Poirot (Paris, FR); Andrew Scharenberg (Seattle, WA); Julianne Smith (Le Plessis Robinson, FR)
Assignee: CELLECTIS
C12N5/0636A61K40/11A61K40/31A61K40/4211C07K14/7051C07K14/70517C07K14/70521C07K14/70578C07K16/28C07K16/2803C12N15/85A61K38/00C07K2317/14C07K2317/24C07K2317/569C07K2317/622C07K2319/00C07K2319/03C07K2319/74C12N2501/39C12N2501/51C12N2501/515C12N2501/599C12N2502/99C12N2510/00
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Quick Facts
Patent No.
US 12,680,076
App. No.
18/056,544
Filed
Nov 17, 2022
Granted
Jul 14, 2026
Kind
B2
Art Unit
1631
USPC
424/93.21
Abstract

The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

Claims (11)

1 . A T-cell comprising a first gene selectively inactivated by DNA cleavage by a first rare-cutting nuclease, wherein said first rare-cutting nuclease is a first TALE-nuclease directed against a PDCD1 (PD1) gene, wherein said first TALE-nuclease is directed against one of the gene target sequences of the PD-1 gene selected from the group consisting of SEQ ID NO:77 and SEQ ID NO:78, and wherein

(a) said first TALE-nuclease comprises amino acid sequences selected from the group consisting of (i) SEQ ID NOs:85 and 86, and (ii) SEQ ID NOs:87 and 88; and/or

(b) said first TALE-nuclease comprises amino acid sequences encoded by nucleic acid sequences selected from the group consisting of (i) SEQ ID NOs:95 and 96, and (ii) SEQ ID NOs:97 and 98.

2 . The T-cell of claim 1 , further comprising a second gene selectively inactivated by DNA cleavage by a second rare-cutting nuclease, wherein said second rare-cutting nuclease is a second TALE-nuclease directed against a CTLA-4, LAG3, or TIGIT gene.

3 . The T-cell according to claim 1 , further comprising a second gene selectively inactivated by DNA cleavage by a second rare-cutting nuclease, wherein said second rare-cutting nuclease is a second TALE-nuclease directed against a Tim3, BTLA, BY55 (CD160), TIGIT, B7H5, LAIR1, SIGLEC10, or 2B4 gene.

4 . The T-cell according to claim 2 , wherein each of the first and the second rare-cutting nucleases are encoded by RNA.

5 . The T-cell according to claim 4 , wherein each of the first and the second rare-cutting nucleases are introduced into said T-cell by way of RNA electroporation.

6 . The T-cell according to claim 2 , wherein said second TALE-nuclease is directed against one of the gene target sequences of CTLA-4 selected from the group consisting of SEQ ID NO:74, SEQ ID NO:75, and SEQ ID NO:76.

7 . The T-cell according to claim 6 , wherein:

(a) said second TALE-nuclease comprises amino acid sequences selected from the group consisting of (i) SEQ ID NOs: 79 and 80, (ii) SEQ ID NOs: 81 and 82, and (iii) SEQ ID NOs:83 and 84; and/or

(b) said second TALE-nuclease comprises amino acids encoded by nucleic acid sequences selected from the group consisting of (i) SEQ ID NOs: 89 and 90, (ii) SEQ ID NOs: 91 and 92, and (iii) SEQ ID NOs: 93 and 94.

Continuity (7)
Continuation 17715218 · Apr 7, 2022
Continuation 14889686 · May 13, 2014
Continuation In Part 13942191 · Jul 15, 2013
Continuation In Part 13892805 · May 13, 2013
Continuation In Part PCTUS2013040766 · May 13, 2013
Continuation In Part PCTUS2013040755 · May 13, 2013
Related Publication 20230201260A1 · Jun 29, 2023
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