Granted Patent
B2
US 12,644,099 · App. 18/084,733 · Granted Jun 2, 2026
Methods for making T cell compositions
Assignee:
2seventy bio, Inc.
C12N5/0636A61K40/11A61K40/31A61K40/4215C07K14/7051C07K16/2878A61K2239/38A61K2239/46A61K2239/48C07K2319/02C07K2319/03C07K2319/74C12N2501/2302C12N2501/51C12N2501/515C12N2501/599C12N2501/727C12N2501/999C12N2510/00
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Abstract
The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.
Claims (21)
1 . A method for manufacturing T cells comprising:
a) activating a population of T cells and stimulating the population of T cells to proliferate, wherein the activation and stimulation steps are performed in the presence of a PI3K inhibitor;
b) transducing the T cells with a viral vector comprising an engineered T cell receptor (TCR) or a chimeric antigen receptor (CAR); and
c) culturing the transduced T cells to proliferate;
wherein the activating and stimulating steps performed in the presence of the PI3K inhibitor results in maintaining proliferation and decreasing differentiation of the transduced T cells compared to the proliferation and differentiation of transduced T cells that were activated and stimulated in the absence of the PI3K inhibitor.
2 . The method of claim 1 , wherein the method comprises isolating peripheral blood mononuclear cells as the source of T cells.
3 . The method of claim 1 , wherein activation of the T cells comprises contacting the T cells with an anti-CD3 antibody or CD3-binding fragment thereof.
4 . The method of claim 1 , wherein stimulation of the T cells comprises contacting the T cells with an anti-CD28 antibody or a CD28-binding fragment thereof, B7-1 or a CD28-binding fragment thereof, or B7-2 or a CD28-binding fragment thereof.
5 . The method of claim 1 , wherein the viral vector is a retroviral vector.
6 . The method of claim 1 , wherein the viral vector is a lentiviral vector.
7 . The method of claim 1 , wherein the CAR comprises an extracellular antigen binding domain comprising an antibody or antigen binding fragment thereof that binds BCMA.
8 . The method of claim 1 , wherein the CAR further comprises a transmembrane domain obtained from CD8ct or CD28.
9 . The method of claim 1 , wherein the CAR comprises one or more costimulatory signaling domains obtained from a polypeptide selected from the group consisting of: CD28, CD134, and CD137.
10 . The method of claim 1 , wherein the CAR further comprises a hinge region polypeptide.
11 . The method of claim 10 , wherein the hinge region polypeptide comprises a hinge region of IgG I or CD8ct.
12 . The method of claim 1 , wherein the CAR further comprises a signal peptide.
13 . The method of claim 12 , wherein the signal peptide comprises an IgG I heavy chain signal polypeptide or a CD8ct signal polypeptide.
14 . The method of claim 1 , wherein the PI3K inhibitor is selected from the group consisting of: BEZ235, LY294002, GDC-0941, BYL719, GSK2636771, TGX-221, AS25242, CAL-101, IPI-145, and ZSTK474.
15 . The method of claim 1 , wherein the PI3K inhibitor is ZSTK474.
16 . The method of claim 1 , wherein manufacturing the T cells in the presence of the PI3K inhibitor increases the number of T cells expressing one or more markers selected from the group consisting of: CD62L, CCR7, CD28, CD27, CD122, and CD127 compared to T cells manufactured according to steps a)-c) performed in the absence of the PI3K inhibitor.
17 . The method of claim 1 , wherein the population of T cells activated and stimulated in the presence of a PI3K inhibitor do not express CD57 or KLRG1 or express less CD57 or KLRG1 compared to a population of T cells activated and stimulated in the absence of the PI3K inhibitor.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 17, 2023
From: FRIEDMAN, KEVIN
To: BLUEBIRD BIO, INC.
Reel/Frame 063666/0052 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 17, 2023
From: BLUEBIRD BIO, INC.
To: 2SEVENTY BIO, INC.
Reel/Frame 063666/0155 →
Continuity (4)
Continuation
15316792
Provisional Application
62008957
· Jun 6, 2014
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