Compositions and Methods for Treatment of Cancer

Patent metadata

Field	Value
Publication number	US-2016208012-A1
Application number	US-201614997136-A
Country	US
Kind code	A1
Filing date	Jan 15, 2016
Priority date	Dec 9, 2010
Publication date	Jul 21, 2016
Grant date	—

Abstract

The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

First claim

1 - 89 . (canceled)

90 . 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 encoding a chimeric antigen receptor (CAR), wherein the CAR comprises a CD19 antigen binding domain comprising from the amino to the carboxy terminus, a light chain variable region and a heavy chain variable region of SEQ ID NO:20, wherein the CAR further comprises a transmembrane domain, a 4-1BB costimulatory signaling region, and a CD3 zeta signaling domain.

91 . The composition of claim 90 , wherein the anti-tumor effective amount of T cells is 10 4 to 10 9 cells per kg body weight of a human in need of such cells.

92 . The composition of claim 90 , wherein the anti-tumor effective amount of T cells is 10 5 to 10 6 cells per kg body weight of a human in need of such cells.

93 . The composition of claim 90 , wherein said antigen binding fragment is a scFv.

94 . The composition of claim 90 , wherein the scFv comprises the amino acid sequence of SEQ ID NO:20.

95 . The composition of claim 90 , wherein the transmembrane domain is CD8α transmembrane domain.

96 . The composition of claim 95 , wherein the CD8α transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22.

97 . The composition of claim 90 , wherein the CAR further comprises a hinge domain.

98 . The composition of claim 97 , wherein the hinge domain is a CD8α hinge domain.

99 . The composition of claim 98 , wherein the CD8α hinge domain comprises the amino acid sequence of SEQ ID NO:21.

100 . The composition of claim 90 , wherein the 4-1BB costimulatory signaling region comprises the amino acid sequence of SEQ ID NO:23.

101 . The composition of claim 90 , wherein the CD3 zeta signaling domain comprises the amino acid sequence of SEQ ID NO: 24.

102 . The composition of claim 90 , wherein the CD19 antigen binding domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 14.

103 . The composition of claim 95 , wherein the CD8α transmembrane domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 16.

104 . The composition of claim 99 , wherein the CD8α hinge domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 15.

105 . The composition of claim 100 , wherein the 4-1BB costimulatory signaling region is encoded by a nucleic acid sequence comprising SEQ ID NO: 17.

106 . The composition of claim 101 , wherein the CD3 zeta signaling domain is encoded by a nucleic acid sequence comprising SEQ ID NO: 18.

107 . The composition of claim 90 , wherein the CAR comprises the amino acid sequence of SEQ ID NO:12.

108 . The composition of claim 107 , wherein the CAR is encoded by a nucleic acid sequence comprising SEQ ID NO:8.

109 . The composition of claim 90 , wherein the CAR further comprises a CD28 costimulatory signaling region.

110 . The composition of claim 90 , wherein the T cells are T cells of a human having a cancer.

111 . The composition of claim 110 , wherein the cancer is a hematological cancer.

112 . The composition of claim 90 , wherein the T cells comprise a vector that comprises the nucleic acid sequence.

113 . The composition of claim 112 , wherein the vector is a lentiviral vector.

114 . The composition of claim 112 , wherein the vector further comprises a promoter.

115 . The composition of claim 114 , wherein the promoter is an EF-1α promoter.

116 . The composition of claim 90 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier, diluent or excipient.

117 . The composition of claim 90 , wherein the pharmaceutical composition comprises a buffer.

118 . The composition of claim 117 , wherein the buffer is neutral buffer saline or phosphate buffered saline.

119 . The composition of claim 90 , wherein the pharmaceutical composition further comprises a carbohydrate.

Assignees

• Univ Pennsylvania

Inventors

• June Carl H
• Levine Bruce L
• Porter David L
• Kalos Michael D
• Milone Michael C

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P37/02

  Immunomodulators · CPC title