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Compound chimeric antigen receptor (cCAR) targeting multiple antigens, compositions and usage method thereof

A chimeric antigen receptor and antigen recognition technology, applied in chemical instruments and methods, biochemical equipment and methods, for targeting specific cell fusion, etc., can solve problems such as the effectiveness and safety of CAR design

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

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Problems solved by technology

There are no general rules for the effectiveness and safety of CAR design

Method used

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  • Compound chimeric antigen receptor (cCAR) targeting multiple antigens, compositions and usage method thereof
  • Compound chimeric antigen receptor (cCAR) targeting multiple antigens, compositions and usage method thereof
  • Compound chimeric antigen receptor (cCAR) targeting multiple antigens, compositions and usage method thereof

Examples

Experimental program
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Effect test

example

[0730] According to the present invention, engineered CD19b-IL-21 (CD19b-IL21) CAR cells ( Figure 33A ). CD19b CAR equipped with IL-2 secretes cleaves leukemia / lymphoma expressing CD19 antigen.

[0731] Peripheral blood mononuclear leukocytes were activated for two to three days and transduced with CD19b-IL-21 or control vector. Three days after transduction, the expression of CD19b-IL-21 on the surface of T cells was demonstrated by staining the transduced T cells with goat anti-mouse Fab antibody and mouse anti-human CD3. Figure 33B It was shown that 63.9% of cells transduced with CD19b-IL-21CAR virus were positive for both F(ab')2 and CD3 as determined by flow cytometry.

[0732] Cell killing assays were performed and targeted cells expressing CD19 were lysed by IL-19-IL-21 CAR.

[0733] In vivo antitumor activity, cell killing in xenogeneic mouse models, and elimination or inhibition of CD19-expressing CD19b-IL-21 CAR T or NK cells using the methods described in PCT / U...

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PUM

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Abstract

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a firsthinge region, a first transmembrane domain, a first co- stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co- stimulatory domain, and a second signaling domain, wherein the first antigen recognition domain is different from the second antigen recognition domain.

Description

[0001] Cross References to Related Applications [0002] This application is based on U.S. Provisional Patent Application No. 62 / 571608, filed October 12, 2017, and U.S. Provisional Patent Application No. 62 / 628973, filed February 10, 2018, 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, expres...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K14/54C07K14/55
CPCC07K14/54C07K14/5443C07K14/55C07K14/705C07K14/70503C07K14/7051C12N15/62C07K2319/00C07K2319/02C07K2319/03C07K16/2803C07K16/2851C07K16/2866C07K16/2878C07K16/2887C07K16/2896C07K16/3084A61K2039/505A61K2039/507C07K2317/622C07K2319/33C12N5/0636A61P35/00A61K35/17C07K14/435C07K14/70514C07K14/70575C07K14/70589C07K14/7155C12N5/0646C12N9/1081C12N2510/00
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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