IP Library › Granted Patent US 12,734,239
Granted Patent B2
US 12,734,239 · App. 16/970,930 · Granted Sep 15, 2026

K562 universal antigen presenting cells and uses thereof

Inventors: Sonny O. T. Ang (Houston, TX); Enli Liu (Houston, TX); Elizabeth Shpall (Houston, TX); Katy Rezvani (Houston, TX)
Assignee: Board of Regents, The University of Texas System
A61K45/06A61K39/39541A61K40/15A61K40/31A61K40/418C07K14/54C07K14/70503C07K14/70575C07K16/2887C12N5/0636C12N5/0646C12N15/86A61K2039/505A61K2239/48C12N2500/90C12N2501/2302C12N2502/30C12N2740/10043
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Quick Facts
Patent No.
US 12,734,239
App. No.
16/970,930
Granted
Sep 15, 2026
Kind
B2
Abstract

Provided herein are universal antigen presenting cells. Also provided herein are methods of expanding immune cells using the UAPCs and methods for the treatment of a disease, such as cancer, using the expanded immune cells.

Claims (74)

1 . A K562 universal antigen presenting cell (UAPC) engineered to express (1) CD48, (2) membrane-bound interleukin-21 (mbIL-21), and (3) 41BB ligand (41BBL), wherein the K562 UAPC is essentially free of expression of endogenous HLA class I, II, or CD1d molecules, wherein the UAPC in co-culture with NK cells induces expansion of the NK cells.

2 . The K562 UAPC of claim 1 , wherein the K562 UAPC expresses CS1.

3 . The K562 UAPC of claim 1 , wherein the K562 UAPC expresses ICAM-1 (CD54) and LFA-3 (CD58).

4 . The K562 UAPC of claim 1 , wherein the K562 UAPC is a leukemia cell-derived UAPC.

5 . The K562 UAPC of claim 1 , wherein the K562 UAPC has been engineered by retroviral transduction.

6 . The K562 UAPC of claim 5 , wherein the retroviral transduction is further defined as transduction using a viral construct of SEQ ID NO: 1 and/or SEQ ID NO:2.

7 . The K562 UAPC of claim 1 , wherein the K562 UAPC is irradiated.

8 . A method for expanding immune cells comprising culturing the immune cells in the presence of an effective amount of K562 UAPCs of claim 1 , wherein the immune cells comprise NK cells.

9 . The method of claim 8 , wherein the immune cells and K562 UAPCs are cultured at a ratio of 3:1 to 1:3.

10 . The method of claim 8 , wherein the immune cells and K562 UAPCs are cultured at a ratio of 1:2.

11 . The method of claim 8 , wherein the expanding is in the presence of IL-2.

12 . The method of claim 11 , wherein the IL-2 is present at a concentration of 10-500 U/mL.

13 . The method of claim 11 , wherein the IL-2 is present at a concentration of 100-300 U/mL.

14 . The method of claim 11 , wherein the IL-2 is present at a concentration of 200 U/mL.

15 . The method of claim 11 , wherein the IL-2 is recombinant human IL-2.

16 . The method of claim 11 , wherein the IL-2 is replenished every 2-3 days.

17 . The method of claim 8 , wherein the K562 UAPCs are added at least a second time.

18 . The method of claim 8 , wherein the immune cells are derived from cord blood (CB), peripheral blood (PB), stem cells, or bone marrow.

19 . The method of claim 8 , wherein the stem cells are induced pluripotent stem cells.

20 . The method of claim 8 , wherein the immune cells are obtained from CB.

21 . The method of claim 20 , wherein the CB is pooled from 2 or more individual cord blood units.

22 . The method of claim 20 , wherein the CB is pooled from 3, 4, 5, 6, 7, or 8 individual cord blood units.

23 . The method of claim 8 , wherein the NK cells are CB mononuclear cells (CBMCs).

24 . The method of claim 8 , wherein NK cells are further defined as CD56+NK cells.

25 . The method of claim 8 , wherein the method is performed in serum-free media.

26 . The method of claim 8 , wherein the immune cells are engineered to express a chimeric antigen receptor (CAR).

27 . The method of claim 26 , wherein the CAR comprises a humanized antigen-binding domain.

28 . The method of claim 26 , wherein the CAR comprises a CD19, CD123, mesothelin, CD5, CD47, CLL-1, CD33, CD99, U5snRNP200, CD200, CS1, BAFF-R, ROR-1, or BCMA antigen-binding domain.

29 . The method of claim 26 , wherein the CAR comprises a CD19 or CD123 antigen-binding domain.

30 . The method of claim 26 , wherein the CAR-expressing immune cells co-express IL-15.

31 . The method of claim 26 , wherein the CAR-expressing immune cells co-express a suicide gene.

32 . The method of claim 31 , wherein the suicide gene is CD20, CD52, EGFRv3, or inducible caspase 9.

33 . A population of expanded immune cells produced according to the methods of claim 8 .

34 . A pharmaceutical composition comprising the population of expanded immune cells of claim 33 and a pharmaceutically acceptable carrier.

35 . A composition comprising an effective amount of the expanded immune cells of claim 33 , for use in the treatment of a disease or disorder in a subject.

36 . A method of treating a disease or disorder in a subject comprising administering a therapeutically effective amount of the expanded immune cells of claim 33 to the subject.

37 . The method of claim 36 , wherein the disease or disorder is cancer, inflammation, graft versus host disease, transplant rejection, an autoimmune disorder, an immunodeficiency disease, a B cell malignancy, or an infection.

38 . The method of claim 37 , wherein the cancer is a leukemia.

39 . The method of claim 38 , wherein the leukemia is an acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), or a chronic myelogenous leukemia (CML).

40 . The method of claim 36 , wherein the immune cells are allogeneic.

41 . The method of claim 36 , wherein the immune cells are autologous.

42 . The method of claim 36 , wherein the disorder is graft versus host disease (GVHD).

43 . The method of claim 36 , wherein the disorder is multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, type I diabetes, systemic lupus erythrematosus, contact hypersensitivity, asthma or Sjogren's syndrome.

44 . The method of claim 36 , wherein the subject is a human.

45 . The method of claim 36 , further comprising administering at least a second therapeutic agent.

46 . The method of claim 45 , wherein the at least a second therapeutic agent is a therapeutically effective amount of an anti-cancer agent, immunomodulatory agent, or an immunosuppressive agent.

47 . The method of claim 46 , wherein the anti-cancer agent is chemotherapy, radiotherapy, gene therapy, surgery, hormonal therapy, anti-angiogenic therapy or immunotherapy.

48 . The method of claim 46 , wherein the immunosuppressive agent is a calcineurin inhibitor, an mTOR inhibitor, an antibody, a chemotherapeutic agent irradiation, a chemokine, an interleukins or an inhibitor of a chemokine or an interleukin.

49 . The method of claim 45 , wherein immune cells and/or the at least a second therapeutic agent are administered intravenously, intraperitoneally, intratracheally, intratumorally, intramuscularly, endoscopically, intralesionally, percutaneously, subcutaneously, regionally, or by direct injection or perfusion.

50 . The method of claim 45 , wherein the second therapeutic agent is an antibody.

51 . The method of claim 50 , wherein the antibody is a monoclonal, bispecific or trispecific antibody.

52 . The method of claim 51 , wherein the antibody is rituximab.

53 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells can induce expansion of the NK cells at a rate of about or any value between any two of about 7 fold or more at day 7 of co-culture, about 40 fold or more at day 9 of co-culture, about 200 fold or more at day 11 of co-culture, about 400 fold or more at day 13 of co-culture, or about 600 fold or more at day 14 of co-culture.

54 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells can induce expansion of the NK cells at a rate of about 800 fold or more at day 14 of co-culture.

55 . The K562 UAPC of claim 1 , wherein the rate of NK cell expansion is calculated using the formula

N

f

=

N

b

e

T

T

D

⁢

ln

⁢

2

,

wherein N f is the final cell number, N b is the starting cell, e=2.71828, T is the time span of culture in hours, and T D is the doubling time in hours.

56 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells induces expansion of the NK cells at a rate greater than an antigen presenting cell not engineered to express CD48.

57 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells induces expansion of the NK cells at a rate greater than an antigen presenting cell engineered to express mbIL-21 and 41BBL.

58 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells induces expansion of the NK cells at a rate greater than an antigen presenting cell engineered to express mbIL-21 and 41BBL and not engineered to express CD48.

59 . The K562 UAPC of claim 1 , wherein the K562 UAPC in co-culture with NK cells can induce expansion of the NK cells at a rate of 10 fold to 1000 fold within 14-21 days of co-culture.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 18, 2020
From: ANG, SONNY O. T.; LIU, ENLI; REZVANI, KATY; SHPALL, ELIZABETH J.
To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 053531/0520 →
Continuity (2)
Provisional Application 62633587 · Feb 21, 2018
Related Publication 20200390815A1 · Dec 17, 2020
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