Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics

Patent metadata

Field	Value
Publication number	US-2022000996-A1
Application number	US-202117387892-A
Country	US
Kind code	A1
Filing date	Jul 28, 2021
Priority date	Dec 20, 2012
Publication date	Jan 6, 2022
Grant date	—

Abstract

Cytotoxic lymphocytes expressing chimeric antigen receptors (CAR) that target and bind small conjugate molecules (SCM) are disclosed, as well as methods of using the cells and the SCMs in the treatment of cancer.

First claim

1 - 48 . (canceled)

49 . A method of killing folate receptor-positive (FR+) cancer cells, which method comprises contacting FR+ cancer cells, the folate receptors of which are bound by fluorescein isothiocyanate-folate (FITC-folate) conjugates, with an effective amount of cytotoxic lymphocytes expressing a chimeric antigen receptor (CAR) that specifically binds FITC.

50 . The method of claim 49 , wherein the CAR is a fusion protein comprising a recognition region, a transmembrane domain, a co-stimulation domain, and an activation signaling domain, and wherein the recognition region of the CAR has binding specificity for FITC.

51 . The method of claim 50 , wherein the recognition region of the CAR is a single chain fragment variable (scFv) region of an anti-FITC antibody.

52 . The method of claim 49 , wherein the FITC-folate conjugates comprise a polyethylene glycol-12 ((PEG) 12 ) linker, and the FITC and the folate are conjugated via the linker (FITC-(PEG) 12 -folate conjugates).

53 . The method of claim 49 , wherein the FITC-folate conjugates comprise an ethylenediamine linker, and the FITC and folate are conjugated via the linker (FITC-ethylenediamine-folate conjugates).

54 . The method of claim 49 , wherein a plurality of the FITC-folate conjugates are not endocytosed by the folate receptors of the FR+ cancer cells.

55 . The method of claim 49 , wherein induction of cytokine storm is reduced.

56 . The method of claim 49 , wherein the method comprises transfecting cytotoxic lymphocytes with a vector encoding the CAR that specifically binds FITC prior to contacting the FR+ cancer cells with the cytotoxic lymphocytes expressing the CAR that specifically binds FITC.

57 . The method of claim 56 , wherein the vector is a lentiviral vector.

58 . The method of claim 49 , wherein the method causes lysis of at least about 18% of the FR+ cancer cells.

59 . The method of claim 49 , wherein the method causes lysis of at least about 29% of the FR+ cancer cells.

60 . The method of claim 49 , wherein the method causes lysis of at least about 51% of the FR+ cancer cells.

61 . The method of claim 49 , wherein the method causes lysis of about 18% of the FR+ cancer cells.

62 . The method of claim 49 , wherein the method causes lysis of about 29% of the FR+ cancer cells.

63 . The method of claim 49 , wherein the method causes lysis of about 51% of the FR+ cancer cells.

64 . The method of claim 49 , wherein the cytotoxic lymphocytes are cytotoxic T lymphocytes.

65 . The method of claim 64 , wherein the CAR is a fusion protein comprising a recognition region, a transmembrane domain, a co-stimulation domain, and an activation signaling domain, and wherein the recognition region of the CAR has binding specificity for FITC.

66 . The method of claim 65 , wherein the recognition region of the CAR is a scFv region of an anti-FITC antibody.

67 . The method of claim 64 , wherein the FITC-folate conjugates comprise a polyethylene glycol-12 ((PEG) 12 ) linker, and the FITC and the folate are conjugated via the linker (FITC-(PEG) 12 -folate conjugates).

68 . The method of claim 64 , wherein the FITC-folate conjugates comprise an ethylenediamine linker, and the FITC and the folate are conjugated via the linker (FITC-ethylenediamine-folate conjugates).

69 . The method of claim 64 , wherein a plurality of the FITC-folate conjugates are not endocytosed by the folate receptors of the FR+ cancer cells.

70 . The method of claim 64 , wherein the induction of cytokine storm is reduced.

71 . The method of claim 64 , wherein the method further comprises transfecting cytotoxic lymphocytes with a vector encoding the CAR that specifically binds FITC prior to contacting the FR+ cancer cells with the cytotoxic lymphocytes expressing the CAR that specifically binds FITC.

72 . The method of claim 71 , wherein the vector is a lentiviral vector.

73 . The method of claim 64 , wherein the method causes lysis of at least about 18% of the FR+ cancer cells.

74 . The method of claim 64 , wherein the method causes lysis of at least about 29% of the FR+ cancer cells.

75 . The method of claim 64 , wherein the method causes lysis of at least about 51% of the FR+ cancer cells.

76 . The method of claim 64 , wherein the method causes lysis of about 18% of the FR+ cancer cells.

77 . The method of claim 64 , wherein the method causes lysis of about 29% of the FR+ cancer cells.

78 . The method of claim 64 , wherein the method causes lysis of about 51% of the FR+ cancer cells.

Assignees

• Purdue Research Foundation

Inventors

• Low Philip S
• Chu Haiyan
• Lee Yong Gu

Classifications

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K40/4202

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

• A61K2239/13

  Antibody-based · CPC title

• A61K2039/5158

  Antigen-pulsed cells, e.g. T-cells · CPC title