CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF

A chimeric antigen receptor and receptor technology, applied in the fields of chimeric antigen receptor polypeptides, chimeric antigen receptors and enhancers, chimeric antigen receptor polypeptides and enhancers, can solve the toxicity of CAR protein cells, etc. question

Active Publication Date: 2018-03-27
ICELL GENE THERAPEUTICS LLC +5
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, overexpressed CAR proteins can be toxic to cells

Method used

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  • CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF
  • CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF
  • CHIMERIC ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF

Examples

Experimental program
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example

[0300] Generate compound CAR (cCAR)

[0301] Construction of CD33CD123cCAR follows figure 1 Schematic diagram in A. It includes the SFFV (spleen focus forming virus) promoter driving the expression of a functional compound CAR (cCAR) with two different CAR units. Antigen receptor orientation, anti-CD33 and anti-CD123 scFv (single-chain variable fragment) nucleotide sequences. The P2A peptide derived from picornaviruses was used due to the efficient mechanism for the kinetics of self-cleavage of bicistronic gene constructs. The self-cleaving P2A peptide was used to link together two independent units in CAR, CD33CAR and CD123CAR during expression. Advantages of this approach over internal ribosome entry sites (IRES) commonly used in the literature include their smaller size and high cleavage efficiency between the two upstream and downstream unit proteins of the 2A peptide. In addition, when using IRES, the use of self-cleavable P2A peptides can avoid the problem of differe...

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Abstract

The present invention relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present invention relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present invention relates to engineered cells having chimeric antigen receptorpolypeptides and an enhancer moiety.

Description

[0001] Cross References to Related Applications [0002] This application is an international PCT application asserting U.S. Provisional Application Nos. 62 / 184,321 filed June 25, 2015; 62 / 235,840 filed October 1, 2015; and October 21, 2015 The priority of Application No. 62 / 244,435 is hereby incorporated by reference in its entirety. Background technique [0003] T cells, a type of lymphocyte, play an important role in cell-mediated immunity. They are distinguished from other lymphocytes, such as B cells and natural killer cells (NK cells), by the presence of the T cell receptor (TCR) on the cell surface. T helper cells, also known as CD4+ T or CD4 T cells, express the CD4 glycoprotein on their surface. Helper T cells are activated upon exposure to peptide antigens presented by MHC (major histocompatibility complex) class II molecules. Once activated, these cells proliferate rapidly and secrete cytokines that modulate the immune response. Cytotoxic T cells, also known as ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/705C07K14/725C07K16/28C07K19/00C12N5/0783
CPCC12N5/0636C12N5/0646C07K16/289C07K14/7051C07K14/5443C07K14/70514C07K16/2803C07K16/2866C07K16/2887C07K16/2878C07K16/2896A61K39/001111A61P35/02C07K2319/02C07K2319/03C07K2319/95A61K2039/5158C07K14/70517C07K14/70521C07K14/70578C07K2319/00C07K2319/50C12N2510/00A61K2039/5156A61P35/00A61P43/00
Inventor 马钰波凯文·平茨蒋迅雅之·瓦达陈凯文
Owner ICELL GENE THERAPEUTICS LLC
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