Compositions and Methods for Treating Cancer with TSLPR-CD19 or TSLPR-CD22 Immunotherapy

Patent metadata

Field	Value
Publication number	US-2021379110-A1
Application number	US-202117354624-A
Country	US
Kind code	A1
Filing date	Jun 22, 2021
Priority date	Jun 22, 2020
Publication date	Dec 9, 2021
Grant date	—

Abstract

Chimeric antigen receptors containing TSLPR-CD19 and TSLPR-CD22 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

First claim

1 . An isolated nucleic acid molecule encoding a TSLPR-CD19 or TSLPR-CD22 tandem chimeric antigen receptor (CAR) comprising at least one extracellular antigen binding domain comprising either a TSLPR-CD19 or a TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the TSLPR-CD19 or TSLPR-CD22 tandem CAR is encoded by a nucleotide sequence comprising SEQ ID NO. 84, 86, 88, 90, 96, or 98.

2 .- 13 . (canceled)

14 . A chimeric antigen receptor (CAR) encoded by the isolated nucleic acid molecule of claim 1 .

15 .- 23 . (canceled)

24 . A vector comprising a nucleic acid molecule of claim 1 .

25 . The vector of claim 24 , wherein the vector is selected from the group consisting of a DNA vector, an RNA vector, a plasmid vector, a cosmid vector, a herpes virus vector, a measles virus vector, a lentivirus vector, an adenoviral vector, a retrovirus vector, and a combination thereof.

26 .- 27 . (canceled)

28 . A cell comprising the vector of claim 24 .

29 .- 31 . (canceled)

32 . A method of making a cell comprising transducing a T cell with a vector of claim 24 .

33 .- 35 . (canceled)

36 . A pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the T cells comprise a nucleic acid sequence that encodes a TSLPR-CD19 or TSLPR-CD22 tandem chimeric antigen receptor (CAR), wherein the CAR comprises at least one extracellular antigen binding domain comprising a TSLPR-CD19 or TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the TSLPR-CD19 or TSLPR-CD22 tandem CAR comprises the amino acid sequence comprising SEQ ID NO: 85, 87, 89, 91, 97, or 99 and wherein the T cells are T cells of a human having a cancer.

37 .- 44 . (canceled)

45 . A method of treating a cancer in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutical composition comprising an anti-tumor effective amount of a population of T cells, wherein the T cells comprise a nucleic acid sequence that encodes a TSLPR-CD19 or TSLPR-CD22 tandem chimeric antigen receptor (CAR), comprising at least one extracellular antigen binding domain comprising a TSLPR-CD19 or TSLPR-CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the TSLPR-CD19 or TSLPR-CD22 tandem CAR comprises the amino acid sequence comprising SEQ ID NO: 85, 87 89, 91, 97, or 99, thereby treating the cancer of the human subject.

46 . The method of claim 45 , wherein the at least one transmembrane domain comprises a transmembrane domain of the alpha, the beta or the zeta chain of a T-cell receptor, a CD8, a CD28, a CD3 epsilon, a CD45, a CD4, a CD5, a CD8, a CD9, a CD16, a CD22, a CD33, a CD37, a CD64, a CD80, a CD86, a CD134, a CD137 and a CD154.

47 .- 48 . (canceled)

49 . The method of claim 45 , wherein the at least one TSLPR-CD19 or TSLPR-CD22 antigen binding domain, the at least one intracellular signaling domain, or both are connected to the at least one transmembrane domain by a linker or a spacer domain.

50 . The method of claim 49 , wherein the linker or the spacer domain is derived from the extracellular domain of CD8 or CD28, and is linked to the transmembrane domain.

51 . The method of claim 45 , wherein the TSLPR-CD19 or TSLPR-CD22 tandem CAR is encoded by a nucleotide sequence comprising SEQ ID NO. 84, 86, 88, 90, 96, or 98 or a sequence with 85%, 90%, 95%, 96%, 97%, 98% or 99% identity thereof.

52 . The method of claim 45 , wherein the at least one intracellular signaling domain further comprises a CD3 zeta intracellular domain.

53 . The method of claim 45 , wherein the at least one intracellular signaling domain comprises a costimulatory domain, a primary signaling domain, or any combination thereof.

54 . The method of claim 53 , wherein the costimulatory domain comprises a functional signaling domain of OX40, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, 4-1BB (CD137), and any combination thereof.

55 . The method of claim 45 , wherein the cancer is a hematological cancer.

56 . The method of claim 55 , wherein the hematological cancer is leukemia, lymphoma or multiple myeloma.

57 . The method of claim 56 , wherein the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML).

58 . The method of claim 56 , wherein the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.

59 . The method of claim 45 , wherein the cancer is an adult carcinoma selected from the group consisting of an oral and pharynx cancer, a digestive system cancer, a respiratory system cancer, a bone and joint cancer, a soft tissue cancer, a skin cancer, a pediatric tumor, a tumor of the central nervous system, a cancer of the breast, a cancer of the genital system, a caner of the urinary system, a cancer of the eye and orbit, a cancer of the endocrine system, a cancer of the brain and other nervous system, and a combination thereof.

Assignees

• Lentigen Tech Inc
• Univ Of Colorado

Inventors

• Schneider Dina
• Dropulic Boro
• Fry Terry James

Classifications

• A61K40/4231

  Cytokines · CPC title

• A61K40/4212

  CD22, BL-CAM, siglec-2 or sialic acid binding Ig-related lectin 2 · CPC title

• A61K40/4211

  CD19 or B4 · CPC title

• A61K40/4202

  Receptors, cell surface antigens or cell surface determinants · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title