Compositions and methods for targeting nicotinic acetylcholine receptor autoantibodies

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...

AI Technical Summary

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 resulting in muscle weakness

[0004] Currently there is no apparent cure for MG; existing treatments such as acetylcholinesterase inhibitors and immunosuppressants are intended to manage and control symptoms

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