US 2026/0174853 A1 · CD70-TARGETED CARS AND ENGINEERED CELLS COMPRISING SAME AND RELATED METHODS

Cd70-targeted cars and engineered cells comprising same and related methods

AssigneeJuno Therapeutics, Inc.

InventorsGeoffrey Patrick O’DONOGHUE, John-Michael Eric WILLIFORD, Nikhil HEBBAR, Andres Adolfo ALVAREZ, Eric William JEFFERY, Douglas Scott JONES, Ruth Amanda SALMON, Cédric CLEYRAT, Pallavur SIVAKUMAR, Erin Elizabeth NEVIUS, Kaya Brady PETERSON, Dean Y. TOY, Brian BELMONT, Madeline WILLIAMS, Rebekah TURK, Felecia Dawn WAGENER

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Abstract

Provided herein are CD70-targeted chimeric antigen receptors (CARs), genetically engineered cells such as T cells containing the same, and related methods and uses of the genetically engineered cells in allogeneic cell therapy. Also provided are T cells that are genetically engineered with a CAR, such as a CD70-targeted CAR, and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

Claims264

Dependent claims

A chimeric antigen receptor (CAR) directed against CD70, wherein the CAR comprises a CD70-binding domain that binds to CD70 comprising a heavy chain only variable (VHH) region, wherein:

(i) the VHH region comprises a CDR-1, CDR-2, and CDR-3 each comprising a sequence that is contained within SEQ ID NO:
1, wherein X is Q or pyroglutamate;
or
(ii) the VHH region comprises a CDR-1, CDR-2, and CDR-3 each comprising a sequence that is contained within SEQ ID NO:27, wherein X is Q or pyroglutamate.

1 more element

A genetically engineered human T cell comprising:

(a) a first genetic disruption in exon 1 of an endogenous TRAC gene located at hg38 genomic coordinates chr14:22,547,528-22,547,548, wherein the first genetic disruption disrupts one or more alleles of the endogenous TRAC gene, and wherein a polynucleotide comprising:
(i) a nucleotide sequence comprising the sequence set forth in SEQ ID NO:71 and (ii) a nucleotide sequence encoding a CAR comprising the amino acid sequence set forth in SEQ ID NO:
38 or SEQ ID NO:
41, wherein X is Q or pyroglutamate, is present in the disrupted endogenous TRAC gene in the genetically engineered human T cell,
(b) a second genetic disruption in exon 2 of an endogenous B2M gene located at hg38 genomic coordinates chr15:44,715,614-44,715,634, wherein the second genetic disruption disrupts one or more alleles of the endogenous B2M gene, and wherein a nucleotide sequence encoding a single chain HLA-E fusion protein comprising the sequence set forth in SEQ ID NO:34 is present in the disrupted endogenous B2M gene in the genetically engineered human T cell under the operable control of an endogenous promoter of the endogenous B2M gene;
and
(c) a third genetic disruption in exon 2 of an endogenous CD70 gene located at hg38 genomic coordinates chr19:6,590,122-6,590,142, wherein the third genetic disruption disrupts all alleles of the endogenous CD70 gene.

4 more elements

A genetically engineered human T cell comprising:

(a) a first genetic disruption in exon 1 of an endogenous TRAC gene located at hg38 genomic coordinates chr14:22,547,528-22,547,548, wherein the first genetic disruption disrupts one or more alleles of the endogenous TRAC gene, and wherein a polynucleotide comprising:
(i) a nucleotide sequence comprising:
(1) a first shRNA comprising the sequence set forth in SEQ ID NO:74, (2) a second shRNA comprising the sequence set forth in SEQ ID NO:73, (3) a third shRNA comprising the sequence set forth in SEQ ID NO:72, and (4) a fourth shRNA comprising the sequence set forth in SEQ ID NO:75;
and
(ii) a nucleotide sequence encoding a CAR targeting CD70 comprising the sequence set forth in SEQ ID NO:
38 or SEQ ID NO:
41, wherein X is Q or pyroglutamate, is present in the disrupted TRAC gene in the genetically engineered human T cell,
(b) a second genetic disruption in exon 2 of an endogenous B2M gene located at hg38 genomic coordinates chr15:44,715,614-44,715,634, wherein the second genetic disruption disrupts one or more alleles of the endogenous B2M gene, and wherein the first nucleotide sequence encoding a single chain HLA-E fusion protein comprising the sequence set forth in SEQ ID NO:34 is present in the disrupted endogenous B2M gene in the genetically engineered human T cell under the operable control of an endogenous promoter of the endogenous B2M gene;
and
(c) a third genetic disruption in exon 2 of an endogenous CD70 gene located at hg38 genomic coordinates chr19:6,590,122-6,590,142, wherein the third genetic disruption disrupts all alleles of the endogenous CD70 gene.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application

19/427,047Filed 19 Dec 2025

Priority

20 Dec 2024

Published

25 Jun 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification30 codes

A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 31/47
Having six-membered rings with one nitrogen as the only ring hetero atom: quinolines; Isoquinolines
A61K 31/4709
Quinolines; Isoquinolines: non-condensed quinolines and containing further heterocyclic rings