T cells modified with synthetic receptors containing single ITAM signaling motif

A signaling, genetic modification technology for biotechnology and cell therapy applications

Pending Publication Date: 2022-07-08
NAT UNIV OF SINGAPORE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Allogeneic "off-the-shelf" products can overcome these challenges, but allogeneic T cells pose a significant risk of graft-versus-host disease (GvHD)

Method used

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  • T cells modified with synthetic receptors containing single ITAM signaling motif
  • T cells modified with synthetic receptors containing single ITAM signaling motif
  • T cells modified with synthetic receptors containing single ITAM signaling motif

Examples

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Embodiment Construction

[0047] The inventors of the present application have discovered that in genetically modifying T cells, in particular αβ T cells, to express a co-stimulatory signaling domain containing at least one co-stimulatory signaling domain and containing only one immunoreceptor tyrosine-based activation motif (ITAM) Genetically modified T cells exhibit enhanced cell expansion, reduced cytokine release, and reduced xenograft-versus-host disease (GvHD) following intracellular signaling domain chimeric antigen receptor (CAR).

[0048] Accordingly, in one example, the present invention relates to a recombinant chimeric antigen receptor (CAR), wherein the recombinant CAR comprises: (a) an extracellular domain comprising an antigen binding region, (b) a transmembrane domain, ( c) at least one costimulatory signaling domain, and (d) an intracellular signaling domain, wherein the extracellular domain comprises the extracellular domain of NK cell activating receptor or the scFv of a monoclonal an...

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Abstract

The present invention relates to [alpha] [beta] T cells genetically modified to express a recombinant chimeric antigen receptor (CAR) wherein the recombinant CAR comprises (a) an extracellular domain comprising an antigen binding region, (b) a transmembrane domain, (c) a co-stimulatory signaling domain, and (d) an intracellular signaling domain wherein the extracellular domain comprises an extracellular domain of the NKG2D receptor, and wherein the intracellular signaling domain comprises an immune receptor tyrosine-based activation motif (ITAM); a recombinant CAR for modifying an alpha beta T cell; a pharmaceutical composition comprising genetically modified [alpha] [beta] T cells; methods of treating cancer or tumors using the genetically modified [alpha] [beta] T cells; and methods of making genetically modified alpha beta T cells. In one embodiment, a genetically modified [alpha] [beta] T cell comprises a CAR comprising an extracellular domain of the NKG2D receptor, an IgG4 hinge region, a CD28 transmembrane domain, a 4-1BB co-stimulatory signaling domain, and a DAP 12 domain comprising a single ITAM.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of priority from Singapore Application No. 10201908256R, filed on September 6, 2019, the contents of which are incorporated herein by reference in their entirety for all purposes. technical field [0003] The present invention generally relates to the fields of biotechnology and cell therapy. In particular, the present invention relates to recombinant chimeric antigen receptors for cancer immunotherapy, genetically modified alpha beta T cells, methods for their preparation and use in patients in need. Background technique [0004] In recent years, tremendous progress has been made in the use of immune effector cells for cancer therapy. Cancer immunotherapy using genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) is an effective approach to treat a variety of blood cancers. CARs consist of an extracellular antigen-binding domain (usually a single-chain ...

Claims

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Application Information

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IPC IPC(8): C12N5/0783
CPCA61P35/00C07K2319/02C07K2319/03C07K14/705C07K14/70521C07K14/7056C07K14/70596C07K2319/00C07K2319/33C12N2510/00C07K2317/53A61K39/464429A61K2239/38A61K39/4631A61K2239/31A61K39/4611A61K2239/59
Inventor 王树黄宇阳李振东郑真康
Owner NAT UNIV OF SINGAPORE
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