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Chimeric antigen receptors (CARs), compositions and methods thereof

A chimeric antigen receptor and antigen recognition technology, which has been successfully applied in diseases and lymphomas, and can solve the problems of toxicity of CAR protein cells.

Pending Publication Date: 2020-06-05
ICELL GENE THERAPEUTICS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 thereof
  • Chimeric antigen receptors (CARs), compositions and methods thereof
  • Chimeric antigen receptors (CARs), compositions and methods thereof

Examples

Experimental program
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example

[0939] cCAR targeting engineered cells expressing CD33 or CD123 or both

[0940] Construction of CD33CD123 cCAR follows figure 1 and Figure 2A The diagram in the middle. It includes the SFFV (spleen focus forming virus) promoter driving the expression of a functional composite 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, CD33 CAR and CD123 CAR 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 s...

Embodiment

[1056] Example: CD45b-28-2G-4-1BBL is generated, and the generated CD45bCAR cells can accept costimulatory pathways, CD28 and 4-1BB. CD45b-28-2G-4-1BBL virus was concentrated 4-fold and used to transduce NK45i-92 cells. Its CAR surface expression is about 87% ( Figure 58B ). CD45b-28-2G-4-1BBL virus was concentrated 4-fold and used for transduction. The antitumor activity of CD45b-2GCAR cells was significantly improved when 4-1BBL was included in the construct.

[1057] The enhancer IL-15 / IL-15sushi was also included in the CD45CAR construct as an alternative method to enhance the antitumor activity of CD45CAR. Both CD45CAR and IL-15 / IL-15sushi are in a single construct (Figure 58). The antitumor activity of CD45b-2GCAR cells was significantly enhanced when IL-15 / IL-15sushi was included in the construct.

[1058] Example: Generation of CD45b-28-2G-IL-15 / IL-15sushiNK cells. Surface CD45bCAR expression was approximately 60%. ( Figure 58C ). The antitumor activity of C...

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Abstract

The present disclosure provides chimeric antigen receptors (CARs), compositions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

Description

[0001] Cross References to Related Applications [0002] This application is based on the benefit of prior U.S. Provisional Application No. 62 / 523,147, filed June 21, 2017, and U.S. Provisional Application No. 15 / 538,620, filed June 21, 2017, which are hereby incorporated by reference in their 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 CD8+ T cells or CD8 T cells, ex...

Claims

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Application Information

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IPC IPC(8): C12N5/10C07K19/00C12N15/62A61K39/00A61K35/17A61K35/15A61P11/06A61P37/02A61P35/00
CPCA61K2039/505A61K2039/507A61K2039/545C07K14/5443C07K14/7051C07K14/70517C07K14/70521C07K14/70578C07K16/2803C07K16/2812C07K16/2851C07K16/2866C07K16/2878C07K16/2887C07K16/289C07K16/2893C07K16/2896C07K16/3084C07K16/4291C07K2317/31C07K2317/622C07K2317/73C07K2319/02C07K2319/03C07K2319/33C12N5/0636C12N2510/00A61P11/06A61P29/00A61P37/00A61P35/02A61K39/4631A61K39/464411A61K39/464463A61K2239/38A61K39/464402A61K39/464424A61K2239/48A61K39/464417A61K39/464471A61K39/4613A61K39/464413A61K2239/31A61K39/464412A61K2239/28A61K39/4611A61K39/4635A61P37/06A61P35/00A61K35/17A61K38/00C07K16/28C07K16/3061C07K2319/74
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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