Chimeric antigen receptors and methods for reducing toxicity

Patent metadata

Field	Value
Publication number	US-2024148826-A1
Application number	US-202318329365-A
Country	US
Kind code	A1
Filing date	Jun 5, 2023
Priority date	Jan 26, 2018
Publication date	May 9, 2024
Grant date	—

Abstract

Nucleic acid molecules that include a nucleotide sequence encoding a chimeric antigen receptor (CAR) and a nucleotide sequence encoding a protease sensitive scFv, wherein the chimeric antigen receptor comprises: an scFv targeting a tumor antigen, a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3 ζ signaling domain; and the protease-sensitive scFv and the scFv target the same tumor antigen are described.

First claim

1 . A nucleic acid molecule comprising:
a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising: an scFv comprising a VH domain comprising SEQ ID NO: 33 and a VL domain SEQ ID NO:34, a spacer comprising an amino acid sequence of any one of SEQ ID NOs: 2-12, a transmembrane domain comprising an amino acid sequence of any one of SEQ ID NOs: 13-20, a co-stimulatory domain comprising an amino acid sequence of any one of SEQ ID NOs: 22-25, and a CD3 ζ signaling domain.

2 . A nucleic acid molecule encoding a protease sensitive scFv comprising a VH domain comprising SEQ ID NO: 33 and a VL domain SEQ ID NO:34 joined by a protease-sensitive linker that is sensitive to MMP-2 or MMP-9.

Assignees

• Hope City

Inventors

• Wang Xiuli
• Forman Stephen J
• Stern Lawrence
• Brown Christine E
• Cohen Joseph

Classifications

• A61K40/4248

  Matrix metalloproteinases [MMP] · CPC title

• A61K40/4223

  CD44 not IgG · CPC title

• A61K40/4211

  CD19 or B4 · CPC title

• 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