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Chimeric receptor polypeptides and uses thereof

A technology of chimeric receptors and signal peptides, applied in the field of chimeric receptor polypeptides, can solve problems such as limiting efficacy, increasing T cell differentiation and exhaustion

Pending Publication Date: 2021-07-23
NANJING LEGEND BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the absence of current CAR-T and TCR-T tumor antigens (antigen-independent signaling (tonic signaling)), basal signaling may be important, which can increase T cell differentiation and exhaustion, and limit its effectiveness

Method used

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  • Chimeric receptor polypeptides and uses thereof
  • Chimeric receptor polypeptides and uses thereof
  • Chimeric receptor polypeptides and uses thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0240] Preparation of immune cells expressing chimeric receptor polypeptide

[0241] In one aspect, the invention provides immune cells (eg, lymphocytes, eg, T cells) expressing a chimeric receptor polypeptide described herein. Exemplary methods of making immune cells (eg, T cells) expressing chimeric receptor polypeptides are provided herein.

[0242] In some embodiments, one or more nucleic acids (comprising For example, lentiviral vectors) are introduced into immune cells to generate immune cells expressing chimeric receptor polypeptides. Introduction of one or more nucleic acids into immune cells can be accomplished using techniques known in the art. In some embodiments, the immune cells (such as T cells) of the invention are capable of replicating in vivo, resulting in long-term persistence, which can lead to sustained control of diseases (such as cancer, autoimmune diseases, or viral diseases) associated with the expression of target antigens. Infect).

[0243] In so...

Embodiment 1

[0324] Embodiment 1. A chimeric receptor polypeptide comprising:

[0325] a) an extracellular target binding domain;

[0326] b) an extracellular TCR binding domain;

[0327] c) a transmembrane domain comprising the transmembrane domain of the first TCR subunit; and

[0328] d) optionally, an intracellular domain comprising an intracellular domain of a second TCR subunit,

[0329] Wherein the first TCR subunit and the second TCR subunit are both selected from the group consisting of CD3ε, CD3γ, CD3δ, TCRα, TCRβ, TCRγ and TCRδ.

Embodiment 2

[0330] Embodiment 2. The chimeric receptor polypeptide of embodiment 1, wherein the extracellular TCR binding domain comprises a TCR antigen binding domain that specifically recognizes a TCR subunit selected from the group consisting of: TCRα, TCRβ, TCRγ, TCRδ, CD3ε, CD3δ, CD3γ, and CD3ζ.

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Abstract

Provided is a chimeric receptor polypeptide comprising: a) an extracellular target binding domain; b) an extracellular TCR binding domain; c) a transmembrane domain comprising a transmembrane domain of a first TCR subunit; and / or d) an intracellular domain comprising an intracellular domain of a second TCR subunit. Also provided are nucleic acids encoding such chimeric receptor polypeptide and immune cells expressing such chimeric receptor polypeptide and uses thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to International Patent Application No. PCT / CN2019 / 071609 filed on January 14, 2019, the contents of which are incorporated herein by reference in their entirety. [0003] Sequence listings are submitted as ASCII text files [0004] The following submission as an ASCII text file is hereby incorporated by reference in its entirety: Sequence Listing in Computer Readable Form (CRF) (File Name: 761422001541SEQLIST.TXT, Date of Record: January 10, 2020, Size: 152KB). technical field [0005] The present invention relates to chimeric receptor polypeptides comprising an extracellular target binding domain, an extracellular T cell receptor (TCR) binding domain, a transmembrane domain, and / or an intracellular signaling domain. Background technique [0006] The development and function of all T cells depend on their antigen receptors. The T cell receptor (TCR) is a multiprotein complex comprisi...

Claims

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Application Information

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IPC IPC(8): A61K48/00C12N15/861C07K19/00C12N15/62C12N15/867C12N15/65C12N5/10
CPCC07K14/7051C12N2510/00C12N5/0636A61P35/00C07K2317/622C12N15/86C12N2740/16043C07K2319/33C07K2319/03C07K16/2878C07K2317/31C07K16/2809A61K39/4632A61K39/464417A61K39/4611C07K14/705C12N15/62C07K2317/569C07K2319/02A61K35/17A61K38/00A61K2039/5156A61K2039/5158C07K2317/76
Inventor 曾明张辉辉
Owner NANJING LEGEND BIOTECH CO LTD
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