Compositions and methods for targeting nicotinic acetylcholine receptor autoantibodies

A technology of autoantibodies and receptors, applied in the field of composition of diseases, can solve problems such as muscle weakness, loss, and no obvious cure for MG

Pending Publication Date: 2022-02-22
PORTON BIOLOGICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Binding of anti-nAChR antibodies to nAChR results in complement-mediated loss of the postsynaptic structure and internalization of the receptor, thereby disrupting neuromuscular transmission and resul

Method used

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  • Compositions and methods for targeting nicotinic acetylcholine receptor autoantibodies
  • Compositions and methods for targeting nicotinic acetylcholine receptor autoantibodies
  • Compositions and methods for targeting nicotinic acetylcholine receptor autoantibodies

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[0130] While the present disclosure has been particularly shown and described with reference to specific embodiments, some of which are preferred, it should be understood by those skilled in the art that other modifications may be made without departing from the spirit and scope of the present disclosure disclosed herein. Various changes in form and detail have been made therein.

example 1

[0132] Expression of CAAR in human primary T cells .Design and generate CAAR constructs of interest ( figure 2 ). Primary human T cells were cultured, expanded, stimulated, and transduced with CAAR or mock-transduced. Validation of cell surface expression of CAAR in engineered T cells (CAAR T cells).

[0133] CAAR In vitro efficacy testing of T cells . CAAR T cells (or control T cells) were co-cultured with cells expressing anti-nAChR BCR (target cells). Cells of interest, such as hybridoma cells, are generated in-house or purchased from ATCC (eg, 5A1-2A8 cells, accession number PTA-8513; 1H11-2E10 cells, accession number PTA-8512; mAb35 cells, accession number TIB-175). Cytotoxicity is calculated based on the percentage lysis of target cells. CAAR T cells specifically kill target cells, but not non-target cells, indicating the specificity of CAAR T cells to kill target cells.

[0134] In vivo efficacy testing of CAART cells. After pretreatment of mice with intraven...

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Abstract

The present disclosure provides a chimeric autoantibody receptor (CAAR) that is specific for an autoantibody-based B cell receptor (BCR), wherein the autoantibody is specific for nAChR. The disclosure also provides compositions comprising the CAAR, polynucleotides encoding the CAAR, vectors comprising the polynucleotides encoding the CAAR, engineered cells comprising the CAAR, and methods of using the same.

Description

technical field [0001] The present disclosure generally relates to therapies comprising treatment with immunosuppressive drugs. In particular, the present disclosure relates to compositions and methods for treating or preventing disorders associated with anti-nicotinic acetylcholine receptor (nAChR) autoantibodies. Background technique [0002] Myasthenia gravis (MG) is a neuromuscular disorder that causes skeletal muscle weakness. It affects about 14 to 20 people per 100,000 population, with an incidence of about 36,000 to 60,000 cases in the United States. MG can develop at any age. The course of the disease is variable but usually progressive, reaching a maximum in the years after the initial onset. Common symptoms associated with the disease include muscle weakness in the arms or legs, double vision, drooping eyelids, and difficulties with facial expression, speech, chewing, and swallowing. Severe weakness of the muscles that control breathing occurs at least once in...

Claims

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Application Information

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IPC IPC(8): C12N15/62C07K19/00C07K5/10A61K35/17A61P21/04
CPCC07K14/70571A61K35/17A61P21/04C07K2319/02C07K2319/03C07K2319/33A61K2039/5156
Inventor J·王朱世诚陈功孔令洁
Owner PORTON BIOLOGICS LTD
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