Compositions for treatment of autoimmune diseases

Abstract

Provided herein are methods of treating subjects having or suspected of having an autoimmune disease with natural killer (NK) cells, and related compositions, uses, and articles of manufacture. In some aspects, the NK cells express a recombinant receptor, such as a CD19-directed chimeric antigen receptor (CAR).

Description

COMPOSITIONS FOR TREATMENT OF AUTOIMMUNE DISEASESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Application No. 63 / 705459, filed October 9, 2024, United States Provisional Application No. 63 / 789274, filed April 15, 2025, and United States Provisional Application No. 63 / 867453, filed August 20, 2025, the entire contents of each of which is incorporated by reference herein.FIELD

[0002] The present disclosure relates to methods of treating autoimmune diseases with natural killer (NK) cells, and related compositions, uses, and articles of manufacture. The NK cells generally express recombinant receptors, such as chimeric antigen receptors (CARs) for targeting an antigen, such as CD 19. In some embodiments, the subject has or is suspected of having an autoimmune disease (e.g., a B cell-mediated autoimmune disease).BACKGROUND

[0003] Autoimmune diseases include a myriad of heterogenous conditions in which a subject’s immune system attacks the subject’s healthy cells, tissues, and / or organs. B cells contribute to autoimmune disease pathogenesis in multiple ways, including by producing autoantibodies, serving as antigen-presenting cells (APCs), and producing cytokines. Current strategies for treating autoimmune diseases include use of corticosteroids, immunosuppressive agents, and B cell-targeting agents. Such strategies often have limited potency and / or persistence, are not suitable for chronic use, or both. Thus, effective therapies for patients with autoimmune diseases are needed. Provided are methods and uses that meet such needs.INCORPORATION BY REFERENCE OF MATERIAL IN SEQUENCE LISTING FILE

[0004] This application incorporates by reference the material contained in the Sequence Listing XML file being submitted concurrently herewith: File name: NKT.117WO_ST26.xml; created on October 7, 2025 and is 40, 960 bytes in size.SUMMARY

[0005] Provided herein are methods of treating an autoimmune disease, the methods comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19. In some embodiments, the autoimmune disease is a B cell-mediated autoimmune disease.

[0006] Also provided herein are methods of treating an autoimmune disease, the methods comprising administering to a subject having an autoimmune disease a compositioncomprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19.

[0007] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmune disease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any combination thereof. In some embodiments, the autoimmune disease comprises primary membranous nephropathy (pMN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC). In some embodiments, the disease comprises non-infectious scleritis. In some embodiments, the disease comprises non-infectious uveitis. In some embodiments, the disease comprises mixed connective tissue disease (MCTD).

[0008] Also provided herein are methods of reducing B cells in a subject, the methods comprising administering to a subject having a B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19.

[0009] Also provided herein are methods of reducing the level of an autoantibody in a subject having a B cell-mediated disease, the methods comprising administering to a subject having a B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19.

[0010] Also provided herein are methods of reducing B cells in a subject, the methods comprising administering to a subject having a B cell-mediated disease a composition comprisingnatural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19.

[0011] In some embodiments, the B cell-mediated disease is an autoimmune disease. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0012] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmune disease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any combination thereof. In some embodiments, the autoimmune disease comprises primary membranous nephropathy (pMN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC). In some embodiments, the disease comprises non-infectious scleritis. In some embodiments, the disease comprises non-infectious uveitis. In some embodiments, the disease comprises mixed connective tissue disease (MCTD).

[0013] Also provided herein is a method of reducing B cells in a subject having a B cell-mediated disease comprising administering to the subject a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle; and (ii) the method reduces peripheral B cells in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; and / or at least about 75% of repopulating peripheral B cells are non-class-switched B cells. Also provided herein is a methodof reducing B cells in a subject having a B cell-mediated disease comprising administering to the subject a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle; and (ii) the method reduces peripheral B cells in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; and / or at least about 75% of repopulating peripheral B cells are naive B cells. In some embodiments, the method reduces peripheral B cells in the subject by at least about 90%. In some embodiments, peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle. In some embodiments, at least about 75% of repopulating peripheral B cells are non- class-switched B cells. In some embodiments, at least about 75% of repopulating peripheral B cells are naive B cells. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 6 months, 9 months, 12 months, 15 months, 18 months, or 21 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 6 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 9 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 12 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 15 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 18 months after the beginning of the dosing cycle. In some embodiments, at least about 75% of the repopulation peripheral B cells are naive B cells at a time point that is about 21 months after the beginning of the dosing cycle.

[0014] In some embodiments, the B cell-mediated disease is an autoimmune disease. In some embodiments, the genetically engineered NK cells are allogeneic to the subject. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmunedisease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host- disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any combination thereof. In some embodiments, the autoimmune disease comprises primary membranous nephropathy (pMN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC).

[0015] In some embodiments, the autoimmune disease comprises Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In some embodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0016] In some embodiments, the autoimmune disease is refractory to one or more prior lines of therapy.

[0017] In some embodiments, the method reduces B cells in the subject by at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, or at least about 99%. In some embodiments, the method reduces B cells in the subject by at least about 70%. In some embodiments, the method reduces B cells in the subject by at least about 75%. In some embodiments, the method reduces B cells in the subject by at least about 80%. In some embodiments, the method reduces B cells in the subject by at least about 85%. In some embodiments, the method reduces B cells in the subject by at least about 90%.

[0018] In some embodiments, the method reduces B cells in the subject for at least about 30 days, at least about 45 days, at least about 60 days, at least about 75 days, or at least about 90 days. In some embodiments, the method reduces B cells in the subject for at least about 30 days. In some embodiments, the method reduces B cells in the subject for at least about 30 days, at least about 45 days, at least about 50 days, at least about 60 days, at least about 75 days, at least about90 days, at least about 100 days, at least about 125 days, at least about 150 days, at least about 175 days, at least about 200 days, at least about 225 days, at least about 250 days, at least about 300 days, or at least about 350 days. In some embodiments, the method reduces B cells in the subject for at least about 45 days. In some embodiments, the method reduces B cells in the subject for at least about 50 days. In some embodiments, the method reduces B cells in the subject for at least about 60 days. In some embodiments, the method reduces B cells in the subject for at least about75 days. In some embodiments, the method reduces B cells in the subject for at least about 90 days.In some embodiments, the method reduces B cells in the subject for at least about 100 days. In some embodiments, the method reduces B cells in the subject for at least about 125 days. In some embodiments, the method reduces B cells in the subject for at least about 150 days. In some embodiments, the method reduces B cells in the subject for at least about 175 days. In some embodiments, the method reduces B cells in the subject for at least about 200 days. In some embodiments, the method reduces B cells in the subject for at least about 225 days. In some embodiments, the method reduces B cells in the subject for at least about 250 days. In some embodiments, the method reduces B cells in the subject for at least about 300 days. In some embodiments, the method reduces B cells in the subject for at least about 350 days.

[0019] In some embodiments, the method reduces B cells in the subject for about 30 days, about 45 days, at least about 50 days, about 60 days, about 75 days, or about 90 days. In some embodiments, the method reduces B cells in the subject for about 30 days, about 45 days, at least about 50 days, about 60 days, about 75 days, about 90 days, about 100 days, about 125 days, about 150 days, about 175 days, about 200 days, about 225 days, about 250 days, about 300 days, or about 350 days. In some embodiments, the method reduces B cells in the subject for about 30 days. In some embodiments, the method reduces B cells in the subject for about 45 days. In some embodiments, the method reduces B cells in the subject for about 50 days. In some embodiments, the method reduces B cells in the subject for about 60 days. In some embodiments, the method reduces B cells in the subject for about 75 days. In some embodiments, the method reduces B cells in the subject for about 90 days. In some embodiments, the method reduces B cells in the subject for about 100 days. In some embodiments, the method reduces B cells in the subject for about 125 days. In some embodiments, the method reduces B cells in the subject for about 150 days. In some embodiments, the method reduces B cells in the subject for about 175 days. In some embodiments, the method reduces B cells in the subject for about 200 days. In some embodiments, the method reduces B cells in the subject for about 225 days. In some embodiments, the method reduces B cells in the subject for about 250 days. In some embodiments, the method reduces B cells in the subject for about 300 days. In some embodiments, the method reduces B cells in the subject for about 350 days. In some embodiments, the B cells are peripheral B cells.

[0020] In some embodiments, the autoimmune disease is a T cell-mediated autoimmune disease. In some embodiments, the autoimmune disease is a plasma cell-mediated autoimmune disease.

[0021] In some embodiments, the subject is seropositive for an autoantibody. In some embodiments, the autoantibody is associated with an autoimmune disease. In some embodiments, the autoantibody is associated with a B cell-mediated disease. In some embodiments, the autoantibody is an anti-nuclear antibody (ANA). In some embodiments, the autoantibody is an anti- dsDNA antibody. In some embodiments, the autoantibody is an anti-Smith antibody. In some embodiments, the autoantibody is an anti-thyroid antibody. In some embodiments, the autoantibody is an anti-neutrophil cytoplasmic antibody (ANCA). In some embodiments, the autoantibody is an anti-thrombin antibody. In some embodiments, the autoantibody is an anti-citrullinated peptide (CP) antibody. In some embodiments, the autoantibody is an anti-actin antibody. In some embodiments, the autoantibody is an anti-phospholipid antibody. In some embodiments, the autoantibody is an anti-smooth muscle antibody. In some embodiments, the autoantibody is an anti- mitochondrial antibody. In some embodiments, the autoantibody is an anti-ganglioside antibody. In some embodiments, the autoantibody is an anti-signal recognition peptide (SRP) antibody. In some embodiments, the autoantibody is an anti-nicotinic acetylcholine receptor (AChR) antibody. In some embodiments, the autoantibody is an anti-muscle-specific kinase (MuSK) antibody. In some embodiments, the autoantibody is an anti-voltage-gated calcium channel (VGCC) antibody. In some embodiments, the autoantibody is an anti-Vinculin antibody. In some embodiments, the autoantibody is an anti-Hu (ANNA-1) antibody. In some embodiments, the autoantibody is an anti- RF antibody. In some embodiments, the autoantibody is an anti-PLA2R antibody. In some embodiments, the autoantibody is an anti-Dsgl antibody. In some embodiments, the autoantibody is an anti-Dsg3 antibody. In some embodiments, the autoantibody is an BPAG1 antibody. In some embodiments, the autoantibody is an BPAG2 antibody. In some embodiments, the autoantibody is an ASMA antibody. In some embodiments, the autoantibody is an SLA antibody. In some embodiments, the autoantibody is an anti-LMK type 3 antibody. In some embodiments, the autoantibody is an anti-LMK type 1 antibody. In some embodiments, the autoantibody is an anti- LC type 1 antibody. In some embodiments, the autoantibody is an anti-liver cytosol type I antibody. In some embodiments, the autoantibody is an pANCA antibody. In some embodiments, the autoantibody is an anti-NMDAR antibody. In some embodiments, the autoantibody is an anti- AMPA antibody. In some embodiments, the autoantibody is an anti-Caspr2 antibody. In some embodiments, the autoantibody is an anti-GABA-B antibody. In some embodiments, the autoantibody is an anti-GABA-A antibody. In some embodiments, the autoantibody is an AQP4- IgG antibody. In some embodiments, the autoantibody is an anti-[>2GPI antibody. In some embodiments, the autoantibody is an antimitochondrial antibody. In some embodiments, the autoantibody is an anti-gp210 antibody. In some embodiments, the autoantibody is an anti-Ul-ribonucleoprotein antibody. In some embodiments, the autoantibody is an anti-Ro / SSA antibody. In some embodiments, the autoantibody is an anti-La / SSB antibody. In some embodiments, the autoantibody is an anti-rheumatoid factor antibody. In some embodiments, the autoantibody is an anti-centromere antibody. In some embodiments, the autoantibody is an anti-nephrin antibody. In some embodiments, the method reduces the level of an autoantibody in the subject.

[0022] In some embodiments, the subject is seropositive for an anti-EBV antibody.

[0023] In some embodiments, the autoimmune disease is selected from the group consisting of systemic lupus erythematosus (SLE), lupus nephritis (LN), scleroderma, rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), NMDA / NMDAR encephalitis, transverse myelitis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), myelin oligodendrocyte glycoprotein spectrum disorder (MOGSD), idiopathic inflammatory myopathy (IIM; also known as myositis), Sjogren’s disease, pemphigus vulgaris, bullous pemphigoid (BP), membranous nephropathy (MN), immune thrombocytopenia (ITP), Hashimoto’ disease, Grave’ s disease, insulin resistance, type I diabetes, antiphospholipid syndrome, vasculitis, anti-neutrophilic cytoplasmic antibodies (ANCA) vasculitis (AAV), and anti-synthetase syndrome (ASSD). In some embodiments, the autoimmune disease comprises idiopathic inflammatory myopathy (IIM), multiple sclerosis (MS), myasthenia gravis (MG), rheumatoid arthritis (RA), scleroderma, thyroid disease, type 1 diabetes, vasculitis, or any combination thereof. In some embodiments, the autoimmune disease is selected from the group consisting of SLE, LN, scleroderma, MG, IIM, and vasculitis.

[0024] In some embodiments, the autoimmune disease comprises scleroderma. In some embodiments, the autoimmune disease is scleroderma. In some embodiments, the autoimmune disease comprises systemic sclerosis (also known as systemic scleroderma). In some embodiments, the autoimmune disease is systemic sclerosis (also known as systemic scleroderma). In some embodiments, the autoimmune disease comprises localized scleroderma. In some embodiments, the autoimmune disease is localized scleroderma.

[0025] In some embodiments, the autoimmune disease comprises myositis (also known as IIM). In some embodiments, the autoimmune disease is myositis (also known as IIM). In some embodiments, the autoimmune disease is selected from the group consisting of anti-synthetase syndrome (ASSD), overlap myopathy (OM), dermatomyositis (DM), clinically amyopathic dermatomyositis, juvenile myositis (JM), necrotizing myopathy (NM; e.g., necrotizing autoimmune myopathy (or immune-mediated necrotizing myopathy), polymyositis (PM), and sporadic inclusion body myositis (sIBM). In some embodiments, the autoimmune disease is ASSD. In some embodiments, the autoimmune disease is OM. In some embodiments, the autoimmune disease is DM. In some embodiments, the autoimmune disease is JM. In some embodiments, the autoimmune disease is NM. In some embodiments, the autoimmune disease is PM. In some embodiments, the autoimmune disease is sIBM.

[0026] In some embodiments, the autoimmune disease comprises vasculitis. In some embodiments, the autoimmune disease is vasculitis. In some embodiments, the vasculitis is large- vessel vasculitis. In some embodiments, the vasculitis is medium-vessel vasculitis. In some embodiments, the vasculitis is small-vessel vasculitis. In some embodiments, the vasculitis is anti- neutrophilic cytoplasmic autoantibody (ANCA) vasculitis. In some embodiments the ANCA vasculitis is granulomatosis with polyangiitis (GPA). In some embodiments the ANCA vasculitis is microscopic polyangiitis (MPA). In some embodiments the ANCA vasculitis is eosinophilic granulomatosis with polyangiitis (EGPA).

[0027] In some embodiments, the autoimmune disease comprises myasthenia gravis (MG). In some embodiments, the autoimmune disease is MG. In some embodiments, MG is ocular MG. In some embodiments, MG is early-onset generalized MG. In some embodiments, MG is late- onset MG.

[0028] In some embodiments, the autoimmune disease comprises multiple sclerosis (MS). In some embodiments, the autoimmune disease is MS. In some embodiments, MS is primary progressive MS (PPMS). In some embodiments, MS is secondary -progressive MS (SPMS). In some embodiments, MS is relapsing-remitting MS (RRMS).

[0029] In some embodiments, the autoimmune disease comprises systemic lupus erythematosus (SLE). In some embodiments, the autoimmune disease is systemic lupus erythematosus (SLE). In some embodiments, the autoimmune disease is SLE without lupus nephritis (LN).

[0030] In some embodiments, the autoimmune disease comprises lupus nephritis (LN). In some embodiments, the autoimmune disease is lupus nephritis (LN). In some embodiments, the autoimmune disease comprises SLE and LN. In some embodiments, the autoimmune disease is SLE and LN.

[0031] In some embodiments, the autoimmune disease comprises non-infectious scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis.

[0032] In some embodiments, the autoimmune disease comprises non-infectious uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis.

[0033] In some embodiments, the autoimmune disease comprises mixed connective tissue disease (MCTD). In some embodiments, the autoimmune disease is MCTD.

[0034] In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA), autoimmune encephalitis, chronic inflammatory demyelinating polyneuropathy (CIDP), primary progresssive MS (PPMS), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, ankylosing spondylitis, bullous pemphigoid (BP), primary membranous nephropathy (pMN), IgA nephropathy (IgAN; also known as Berger’s Disease), autoimmune hepatitis (AIH), chronic graft-versus host diseases (cGvHD), primary sclerosingcholangitis (PSC), primary biliary cholangitis (PBC), cold agglutinin disease (CAD) and / or IgG4- related disease (IgG4-RD).

[0035] In some embodiments, the autoimmune disease is chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft- versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, and / or warm autoimmune hemolytic anemia (wAIHA).

[0036] In some embodiments, the autoimmune disease is ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and / or warm autoimmune hemolytic anemia (wAIHA). In some embodiments, the autoimmune disease is ankylosing spondylitis (AS). In some embodiments, the autoimmune disease is autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease is chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease is cold agglutinin disease (CAD). In some embodiments, the autoimmune disease is IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease is primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease is primary sclerosing cholangitis (PSC). In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA).

[0037] Also provided herein is a method of reducing B cells in a subject, the method including administering to a subject having a B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of reducing the level of an autoantibody in a subject, the method including administering to a subject having a B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, the B cell-mediated disease is an autoimmune disease. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0038] Also provided herein is a method of treating systemic lupus erythematosus (SLE), the method including administering to a subject having SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) thatbinds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing systemic lupus erythematosus (SLE), the method including administering to a subject determined to be at risk of SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0039] Also provided herein is a method of treating lupus nephritis (LN), the method including administering to a subject having LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing lupus nephritis (LN), the method including administering to a subject determined to be at risk of LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0040] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method including administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing chronic inflammatory demyelinating polyneuropathy (CIDP), the method including administering to a subject determined to be at risk of CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0041] Also provided herein is a method of treating IgA nephropathy (IgAN), the method including administering to a subject having IgAN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing IgA nephropathy (IgAN), the method including administering to a subject determined to be at risk of IgAN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0042] Also provided herein is a method of treating ankylosing spondylitis (AS), the method including administering to a subject having AS a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing ankylosing spondylitis (AS), the method including administering to a subject determined to be at risk of AS a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0043] Also provided herein is a method of treating autoimmune hepatitis (AIH), the method including administering to a subject having AIH a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing autoimmune hepatitis (AIH), the method including administering to a subject determined to be at risk of ATH a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0044] Also provided herein is a method of treating chronic graft-versus-host-disease (cGvHD), the method including administering to a subject having cGvHD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing chronic graft-versus-host-disease (cGvHD), the method including administering to a subject determined to be at risk of cGvHD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0045] Also provided herein is a method of treating cold agglutinin disease (CAD), the method including administering to a subject having CAD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing cold agglutinin disease (CAD), the method including administering to a subject determined to be at risk of CAD a composition comprising natural killer (NK) cells geneticallyengineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0046] Also provided herein is a method of treating IgG4-related disease (IgG4-RD), the method including administering to a subject having IgG4-RD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing IgG4-related disease (IgG4-RD), the method including administering to a subject determined to be at risk of IgG4-RD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0047] Also provided herein is a method of treating primary biliary cholangitis (PBC), the method including administering to a subject having PBC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing primary biliary cholangitis (PBC), the method including administering to a subject determined to be at risk of PBC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0048] Also provided herein is a method of treating primary sclerosing cholangitis (PSC), the method including administering to a subject having PSC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing primary sclerosing cholangitis (PSC), the method including administering to a subject determined to be at risk of PSC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0049] Also provided herein is a method of treating a subject having chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease(cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof, the method including administering to the subject a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0050] Also provided herein is a method of treating multiple sclerosis (MS), the method including administering to a subject having MS a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing multiple sclerosis (MS), the method including administering to a subject determined to be at risk of MS a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0051] Also provided herein is a method of treating non-infectious scleritis, the method including administering to a subject having non-infectious scleritis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing non-infectious scleritis, the method including administering to a subject determined to be at risk of non-infectious scleritis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0052] Also provided herein is a method of treating non-infectious uveitis, the method including administering to a subject having non-infectious uveitis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing non-infectious uveitis, the method including administering to a subject determined to be at risk of non-infectious uveitis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CARcomprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0053] Also provided herein is a method of treating mixed connective tissue disease (MCTD), the method including administering to a subject having MCTD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. Also provided herein is a method of preventing mixed connective tissue disease (MCTD), the method including administering to a subject determined to be at risk of MCTD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0054] Also provided herein is a method of preventing chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof, the method including administering to the subject determined to be at risk of chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4- RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof, a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0055] In some embodiments, the extracellular antigen-binding domain comprises a heavy chain variable region (VH) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively. In some embodiments, the VHcomprises the amino acid sequence set forth in SEQ ID NO:35. In some embodiments, the VL comprises the amino acid sequence set forth in SEQ ID NO: 36. In some embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO:35, and the VL comprises the amino acid sequence set forth in SEQ ID NO:36. In some embodiments, the extracellular antigen-binding domain is a single-chain variable fragment (scFv) comprising the amino acid sequence set forth in SEQ ID NO:37.

[0056] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain.

[0057] Also provided herein is a method of preventing an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR- 1 , a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0058] Also provided herein is a method of preventing an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the genetically engineered NK cells are allogeneic to the subject. In some embodiments, the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0059] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the genetically engineered NK cells are allogeneic to the subject. In some embodiments, the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0060] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1 , a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0061] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine; and (iii) the autoimmune disease is selected from the group consisting of scleroderma, myositis, and vasculitis.

[0062] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine; and (iii) the autoimmune disease is selected from the group consisting of chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipidsyndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

[0063] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and (iii) the autoimmune disease is selected from the group consisting of chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft- versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

[0064] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and (iii) the autoimmune disease is selected from the group consisting of Evans syndrome, an autoimmune podocytopathy, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease.

[0065] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration ofcyclophosphamide and fludarabine; and (iii) the autoimmune disease is selected from the group consisting of mixed connective tissue disease (MCTD), non-infectious scleritis, or non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is non-infectious uveitis.

[0066] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (ii) each of the first, second, and third doses of the dosing cycle comprises between about 2.5 x 109CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells; and (iii) the autoimmune disease affects the skin, muscles, and / or kidneys of the subject . In some embodiments, the autoimmune disease affects the skin of the subject. In some embodiments, the autoimmune disease affects the muscles of the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 3 x 109CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 3 x 109CAR-expressing NK cells and about 4 x 109CAR-expressing NK cells. In some embodiments, the autoimmune disease affects the kidneys of the subject. In some embodiments, the second dose is administered to the subject about 2-4 days after the first dose is administered to the subject, and the third dose is administered to the subject about 2-4 days after the second dose is administered to the subject. In some embodiments, each dose of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4.5 x 109CAR- expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0067] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (ii) each of the first, second, and third doses of the dosing cycle comprises betweenabout 1 x 109CAR-expressing NK cells and about 2.5 x 109CAR-expressing NK cells; (iii) the second dose is administered to the subject about 2-4 days after the first dose is administered to the subject, and the third dose is administered to the subject about 2-4 days after the second dose is administered to the subject; and (iv) about three days prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject is administered a lymphodepleting therapy consisting of a single dose of about 1000 mg / m2 of cyclophosphamide. In some embodiments, each dose of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and about 1 x IO10CAR-expressing NK cells, or between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and about 1 x IO10CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 3 x 108CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises about 1 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1 .5 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3.5 x 109CAR- expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0068] Also provided herein is a method of treating an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (ii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 109CAR-expressing NK cells and about 2.5 x 109CAR-expressing NK cells; (iii) the second dose is administered to the subject about 2-4 days after the first dose is administered to thesubject, and the third dose is administered to the subject about 2-4 days after the second dose is administered to the subject; and (iv) about three days prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject is administered a lymphodepleting therapy consisting of a single dose of about 1000 mg / m2 of cyclophosphamide. In some embodiments, the subject is administered a lymphodepleting therapy consisting of one or more doses of about 25 mg / m2 of Fludarabine. In some embodiments, the subject is administered a lymphodepleting therapy consisting of two doses of about 25 mg / m2 of Fludarabine. In some embodiments, the subject is administered a lymphodepleting therapy consisting of three doses of about 25 mg / m2 of Fludarabine. In some embodiments, the subject is given a lymphodepleting therapy, wherein one or more doses of about 30 mg / m2 of Fludarabine are administered. In some embodiments, the subject is given a lymphodepleting therapy, wherein two or more doses of about 30 mg / m2 of Fludarabine are administered. In some embodiments, the subject is given a lymphodepleting therapy, wherein three or more doses of about 30 mg / m2 of Fludarabine. In some embodiments, each dose of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and about 1 x 1010CAR-expressing NK cells, or between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 3 x 108CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and about 1 x 1010CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells, each inclusive. In some embodiments, each dose of the dosing cycle comprises about 1 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.5 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0069] In some embodiments, the autoimmune disease is a B cell-mediated disease.

[0070] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises Evans syndrome, an autoimmune podocytopathy, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease comprises non- infectious scleritis. In some embodiments, the autoimmune disease comprises non-infectious uveitis. In some embodiments, the autoimmune disease comprises mixed connective tissue disease (MCTD).

[0071] Also provided herein is a method of reducing B cells in a subject, the method comprising administering to a subject having B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain comprising a CD8 alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain. Also provided herein is a method of reducing the level of an autoantibody in a subject, the method comprising administering to a subject having B cell-mediated disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain comprising a CD8 alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain. In some embodiments, the B cell-mediated disease is an autoimmune disease. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0072] In some embodiments, the autoimmune disease is a T cell-mediated disease. In some embodiments, the autoimmune disease is a plasma cell-mediated disease. In some embodiments, the subject is seropositive for an autoantibody. In some embodiments, the autoantibody is associated with the autoimmune disease.

[0073] In some embodiments, the autoimmune disease comprises scleroderma. In some embodiments, the autoimmune disease is scleroderma. In some embodiments, the autoimmune disease comprises systemic sclerosis (also known as systemic scleroderma). In some embodiments, the autoimmune disease is systemic sclerosis (also known as systemic scleroderma). In some embodiments, the autoimmune disease comprises localized scleroderma. In some embodiments, the autoimmune disease is localized scleroderma.

[0074] In some embodiments, the autoimmune disease comprises myositis (also known as UM). In some embodiments, the autoimmune disease is myositis (also known as UM). In some embodiments, the autoimmune disease is selected from the group consisting of anti-synthetase syndrome (ASSD), overlap myopathy (OM), dermatomyositis (DM), clinically amyopathic dermatomyositis, juvenile myositis (JM), necrotizing myopathy (NM), polymyositis (PM), and sporadic inclusion body myositis (sIBM). In some embodiments, the autoimmune disease is ASSD. In some embodiments, the autoimmune disease is OM. In some embodiments, the autoimmune disease is DM. In some embodiments, the autoimmune disease is JM. In some embodiments, the autoimmune disease is NM. In some embodiments, the autoimmune disease is PM. In some embodiments, the autoimmune disease is sIBM.

[0075] In some embodiments, the autoimmune disease comprises vasculitis. In some embodiments, the autoimmune disease is vasculitis. In some embodiments, the vasculitis is large- vessel vasculitis. In some embodiments, the vasculitis is medium-vessel vasculitis. In some embodiments, the vasculitis is small-vessel vasculitis. In some embodiments, the vasculitis is anti- neutrophilic cytoplasmic autoantibody (ANCA) vasculitis. In some embodiments the ANCA vasculitis is granulomatosis with polyangiitis (GPA). In some embodiments the ANCA vasculitis is microscopic polyangiitis (MPA). In some embodiments the ANCA vasculitis is eosinophilic granulomatosis with polyangiitis (EGPA).

[0076] In some embodiments, the autoimmune disease comprises myasthenia gravis (MG). In some embodiments, the autoimmune disease is MG. In some embodiments, MG is ocular MG. In some embodiments, MG is early-onset generalized MG. In some embodiments, MG is late- onset MG.

[0077] In some embodiments, the autoimmune disease comprises multiple sclerosis (MS). In some embodiments, the autoimmune disease is MS. In some embodiments, MS is primary progressive MS (PPMS). In some embodiments, MS is secondary-progressive MS (SPMS). In some embodiments, MS is relapsing-remitting MS (RRMS).

[0078] In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA), autoimmune encephalitis, chronic inflammatory demyelinating polyneuropathy (CIDP), primary progresssive MS (PPMS), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, ankylosing spondylitis, bullous pemphigoid (BP), primary membranous nephropathy (pMN), IgA nephropathy (IgAN; also known as Berger’s Disease), autoimmune hepatitis (AIH), chronic graft-versus host diseases (cGvHD), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), cold agglutinin disease (CAD) and / or IgG4- related disease (IgG4-RD).

[0079] In some embodiments, the autoimmune disease is chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, and / or warm autoimmune hemolytic anemia (wAIHA).

[0080] In some embodiments, the autoimmune disease is ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and / or warm autoimmune hemolytic anemia (wAIHA). In some embodiments, the autoimmune disease is ankylosing spondylitis (AS). In some embodiments, the autoimmune disease is autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease is chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease is cold agglutinin disease (CAD). In some embodiments, the autoimmune disease is IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease is primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease is primary sclerosing cholangitis (PSC). In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA).

[0081] In some embodiments, the autoimmune disease comprises systemic lupus erythematosus (SLE). In some embodiments, the autoimmune disease is systemic lupus erythematosus (SLE). In some embodiments, the SLE does not comprise LN. In some embodiments, the autoimmune disease comprises lupus nephritis (LN). In some embodiments, the autoimmune disease is lupus nephritis (LN). In some embodiments, the autoimmune disease comprises SLE and LN. In some embodiments, the autoimmune disease is SLE or LN.

[0082] In some embodiments, the autoimmune disease comprises Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In someembodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In some embodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0083] Also provided herein is a method of treating systemic lupus erythematosus (SLE), the method comprising administering to a subject having SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0084] Also provided herein is a method of treating lupus nephritis (LN), the method comprising administering to a subject having LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0085] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0086] Also provided herein is a method of treating IgA nephropathy (IgAN), the method comprising administering to a subject having IgAN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19,wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0087] Also provided herein is a method of treating ankylosing spondylitis (AS), the method comprising administering to a subject having AS a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0088] Also provided herein is a method of treating autoimmune hepatitis (AIH), the method comprising administering to a subject having AIH a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0089] Also provided herein is a method of treating chronic graft-versus-host-disease (cGvHD), the method comprising administering to a subject having cGvHD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0090] Also provided herein is a method of treating cold agglutinin disease (CAD), the method comprising administering to a subject having CAD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising aheavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0091] Also provided herein is a method of treating IgG4-related disease (IgG4-RD), the method comprising administering to a subject having IgG4-RD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0092] Also provided herein is a method of treating primary biliary cholangitis (PBC), the method comprising administering to a subject having PBC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen -binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0093] Also provided herein is a method of treating primary sclerosing cholangitis (PSC), the method comprising administering to a subject having PSC a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0094] Also provided herein is a method of treating non-infectious scleritis, the method comprising administering to a subject having non-infectious scleritis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0095] Also provided herein is a method of treating non-infectious uveitis, the method comprising administering to a subject having non-infectious uveitis a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0096] Also provided herein is a method of treating mixed connective tissue disease (MCTD), the method comprising administering to a subject having MCTD a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR- 1 , a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0097] In some embodiments, the transmembrane domain comprises a CD8alpha hinge. In some embodiments, the transmembrane domain comprises a CD8alpha transmembrane region. In some embodiments, the transmembrane domain comprises a CD8alpha hinge and a CD8alpha transmembrane region. In some embodiments, the intracellular signaling domain comprises an intracellular signaling region of 0X40. In some embodiments, the intracellular signaling domain comprises a CD3zeta domain. In some embodiments, the intracellular signaling domain comprises an intracellular signaling region of 0X40 and a CD3zeta domain.

[0098] In some embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO:35. In some embodiments, the VL comprises the amino acid sequence set forth in SEQ ID NO:36. In some embodiments, the VH comprises the amino acid sequence set forth in SEQ ID NO:35, and the VL comprises the amino acid sequence set forth in SEQ ID NO:36. In some embodiments, the extracellular antigen-binding domain comprises the amino acid sequence set forth in SEQ ID NO:37. In some embodiments, the extracellular antigen-binding domain is an scFv comprising the amino acid sequence set forth in SEQ ID NO:37.

[0099] In some embodiments, the CD8alpha hinge comprises the amino acid sequence set forth in SEQ ID NO:6. In some embodiments, the CD8alpha transmembrane region comprises the amino acid sequence set forth in SEQ ID NO:8. In some embodiments, the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO:6, SEQ ID NO:8, and / or SEQ ID NO: 10. In some embodiments, the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO:8 or SEQ ID NO: 10. In some embodiments, the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO: 8. In some embodiments, the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO:6 and SEQ ID NO: 8. In some embodiments, the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, the intracellular signaling region of 0X40 comprises the amino acid sequence set forth in SEQ ID NO: 14. In some embodiments, the CD3zeta domain comprises the amino acid sequence set forth in SEQ ID NO: 16. In some embodiments, the CAR comprises the amino acid sequence set forth in SEQ ID NO:38.

[0100] In some embodiments, the NK cells genetically engineered to express a CAR are also engineered to express interleukin- 15 (IL 15). In some embodiments, the NK cells genetically engineered to express a CAR also express a membrane-bound interleukin- 15 (mbIL15). In some embodiments, the mbILl 5 comprises the amino acid sequence set forth in SEQ ID NO:22. In some embodiments, the mbIL15 comprises the amino acid sequence set forth in SEQ ID NO:23. In some embodiments, the mbIL15 comprises the amino acid sequence set forth in SEQ ID NO:40. In some embodiments, the CAR and the mbIL15 are bicistronically encoded by the same nucleic acid molecule. In some embodiments, the nucleic acid sequences encoding the CAR and the mbIL15 are separated by a nucleic acid sequence encoding a T2A peptide. In some embodiments, the T2A peptide comprises the amino acid sequence set forth in SEQ ID NO:20.

[0101] In some embodiments, the NK cells are derived from peripheral blood mononuclear cells (PBMCs). In some embodiments, the NK cells are not derived from cord blood. In some embodiments, the NK cells are not derived from induced pluripotent stem cells (iPSCs).

[0102] In some embodiments, the NK cells are allogeneic to the subject. In some embodiments, the NK cells are obtained from a donor that does not have a B cell-mediated disease. In some embodiments, the NK cells are obtained from a donor that does not have an autoimmune disease. In some embodiments, the NK cells are obtained from a donor that does not have the disease to be treated.

[0103] In some embodiments, the NK cells genetically engineered to express a CAR are also genetically edited. In some embodiments, the NK cells are genetically edited to increase IL15 signaling. In some embodiments, the methods comprise genetically editing the NK cells to increase IL15 signaling. In some embodiments, the NK cells are genetically edited to reduce expression of the CISH gene. In some embodiments, the methods comprise genetically editing the NK cells to reduce expression of the CISH gene. In some embodiments, the NK cells are geneticallyedited to reduce expression of the Cis protein. In some embodiments, the methods comprise genetically editing the NK cells to reduce expression of the Cis protein. In some embodiments, the NK cells comprise a disruption in one or both alleles of the CISH gene. In some embodiments, the NK cells comprise a disruption in one allele of the CISH gene. In some embodiments, the NK cells comprise a disruption in both alleles of the CISH gene.

[0104] In some embodiments, the composition comprising NK cells genetically engineered to express a CAR, is administered to the subject in a dosing regimen comprising a dosing cycle. In some embodiments, the dosing cycle comprises a first dose, a second dose, and a third dose of the composition each comprising NK cells genetically engineered to express a CAR.

[0105] In some embodiments, the second dose is administered to the subject between about 5 days after and about 10 days after the first dose is administered to the subject. In some embodiments, the third dose is administered to the subject between about 5 days after and about 10 days after the second dose is administered to the subject. In some embodiments, the second dose is administered about 7 days after the first dose is administered to the subject. In some embodiments, the third dose is administered about 7 days after the second dose is administered to the subject. In some embodiments, the second dose is administered about 7 days after the first dose is administered to the subject, and the third dose is administered about 7 days after the second dose is administered to the subject.

[0106] In some embodiments, the second dose is administered to the subject between about 2 days after and about 4 days after the first dose is administered to the subject. In some embodiments, the third dose is administered to the subject between about 2 days after and about 4 days after the second dose is administered to the subject. In some embodiments, the second dose is administered about 3 days after the first dose is administered to the subject. In some embodiments, the third dose is administered about 4 days after the second dose is administered to the subject. In some embodiments, the second dose is administered about 3 days after the first dose is administered to the subject, and the third dose is administered about 4 days after the second dose is administered to the subject.

[0107] In some embodiments, the dosing cycle is between about 21 days and about 49 days, each inclusive. In some embodiments, the dosing cycle is between about 14 days and about 35 days, or between about 21 days and about 28 days, each inclusive. In some embodiments, the dosing cycle is about 14 days. In some embodiments, the dosing cycle is about 21 days. In some embodiments, the dosing cycle is about 28 days. In some embodiments, the dosing cycle is about 35 days. In some embodiments, the dosing cycle is about 42 days. In some embodiments, the dosing cycle is about 42 days. In some embodiments, the dosing cycle is about 42 days. In some embodiments, the dosing cycle is about 49 days.

[0108] In some embodiments, the first dose is administered on about Day 0 of the dosing cycle. In some embodiments, the second dose is administered on about Day 7 of the dosingcycle. In some embodiments, the third dose is administered on about Day 14 of the dosing cycle. In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 7 of the dosing cycle, and the third dose is administered on about Day 14 of the dosing cycle.

[0109] In some embodiments, the first dose is administered on about Day 0 of the dosing cycle. In some embodiments, the second dose is administered on about Day 2 of the dosing cycle. In some embodiments, the second dose is administered on about Day 3 of the dosing cycle.In some embodiments, the third dose is administered on about Day 4 of the dosing cycle. In some embodiments, the third dose is administered on about Day 5 of the dosing cycle. In some embodiments, the third dose is administered on about Day 6 of the dosing cycle. In some embodiments, the third dose is administered on about Day 7 of the dosing cycle. In some embodiments, each dose is separated by between about 24 hours and about 72 hours. In some embodiments, each dose is separated by at least about 24 hours. In some embodiments, each dose is separated by about 24 hours. In some embodiments, each dose is separated by at least about 48 hours. In some embodiments, each dose is separated by about 48 hours. In some embodiments, each dose is separated by at least about 72 hours. In some embodiments, each dose is separated by about 72 hours.

[0110] In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 2 of the dosing cycle, and the third dose is administered on about Day 4 of the dosing cycle. In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 2 of the dosing cycle, and the third dose is administered on about Day 5 of the dosing cycle. In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 3 of the dosing cycle, and the third dose is administered on about Day 5 of the dosing cycle. In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 3 of the dosing cycle, and the third dose is administered on about Day 6 of the dosing cycle. In some embodiments, the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 3 of the dosing cycle, and the third dose is administered on about Day 7 of the dosing cycle.

[0111] Also provided herein is a method of treating systemic lupus erythematosus (SLE), the method comprising administering to a subject having SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x IO9CAR-expressing NK cells, about 1.5 x IO9CAR-expressing NK cells, about 2 x IO9CAR-expressing NK cells, or about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x I O8CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x IO9CAR-expressing NK cells.

[0112] Also provided herein is a method of treating systemic lupus erythematosus (SLE), the method comprising administering to a subject having SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0113] Also provided herein is a method of treating lupus nephritis (LN), the method comprising administering to a subject having LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (!) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a lightchain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8 alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x IO9CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x IO8CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x IO9CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x IO9CAR-expressing NK cells.

[0114] Also provided herein is a method of treating lupus nephritis (LN), the method comprising administering to a subject having LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0115] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express achimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x IO9CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0116] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapycomprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0117] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0118] Also provided herein is a method of treating IgA nephropathy (IgAN), the method comprising administering to a subject having IgA nephropathy (IgAN) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (!) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x 1010CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressingNK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0119] Also provided herein is a method of treating IgA nephropathy (IgAN), the method comprising administering to a subject having IgA nephropathy (IgAN) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of lludarabine.

[0120] Also provided herein is a method of treating IgA nephropathy (IgAN), the method comprising administering to a subject having IgA nephropathy (IgAN) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine. Also provided herein is a method of treating ankylosing spondylitis (AS), the method comprising administering to a subject having ankylosing spondylitis (AS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses ofthe dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0121] Also provided herein is a method of treating ankylosing spondylitis (AS), the method comprising administering to a subject having ankylosing spondylitis (AS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0122] Also provided herein is a method of treating ankylosing spondylitis (AS), the method comprising administering to a subject having ankylosing spondylitis (AS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0123] Also provided herein is a method of treating antiphospholipid syndrome (APS), the method comprising administering to a subject having antiphospholipid syndrome (APS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cellsgenetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 10’ CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x 1 O10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0124] Also provided herein is a method of treating antiphospholipid syndrome (APS)the method comprising administering to a subject having antiphospholipid syndrome (APS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0125] Also provided herein is a method of treating antiphospholipid syndrome (APS), the method comprising administering to a subject having antiphospholipid syndrome (APS) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has beenadministered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0126] Also provided herein is a method of treating autoimmune encephalitis (AE), the method comprising administering to a subject having autoimmune encephalitis (AE) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x 10, nCAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0127] Also provided herein is a method of treating autoimmune encephalitis (AE) the method comprising administering to a subject having autoimmune encephalitis (AE) acomposition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0128] Also provided herein is a method of treating autoimmune encephalitis (AE), the method comprising administering to a subject having autoimmune encephalitis (AE) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0129] Also provided herein is a method of treating autoimmune hepatitis (AIH), the method comprising administering to a subject having autoimmune hepatitis (AIH) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 xIO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0130] Also provided herein is a method of treating autoimmune hepatitis (AIH) the method comprising administering to a subject having autoimmune hepatitis (AIH) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0131] Also provided herein is a method of treating autoimmune hepatitis (AIH), the method comprising administering to a subject having autoimmune hepatitis (AIH )a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0132] Also provided herein is a method of treating IgG4-related disease (IgG4-RD), the method comprising administering to a subject having IgG4-related disease (IgG4-RD)a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 10sCAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after thesecond dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some each of embodiments, the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0133] Also provided herein is a method of treating IgG4-related disease (IgG4-RD) the method comprising administering to a subject having IgG4-related disease (IgG4-RD) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0134] Also provided herein is a method of treating IgG4-related disease (IgG4-RD), the method comprising administering to a subject having IgG4-related disease (IgG4-RD) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0135] Also provided herein is a method of treating cold agglutinin disease (CAD), the method comprising administering to a subject having cold agglutinin disease (CAD) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acidsequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 10’ CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0136] Also provided herein is a method of treating cold agglutinin disease (CAD)the method comprising administering to a subject having cold agglutinin disease (CAD) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0137] Also provided herein is a method of treating cold agglutinin disease (CAD), the method comprising administering to a subject having cold agglutinin disease (CAD) acomposition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0138] Also provided herein is a method of treating primary biliary cholangitis (PBC), the method comprising administering to a subject having primary biliary cholangitis (PBC)a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CDSalpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressingNK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0139] Also provided herein is a method of treating primary biliary cholangitis (PBC) the method comprising administering to a subject having primary biliary cholangitis (PBC) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0140] Also provided herein is a method of treating primary biliary cholangitis (PBC), the method comprising administering to a subject having primary biliary cholangitis (PBC) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0141] Also provided herein is a method of treating primary sclerosing cholangitis (PSC), the method comprising administering to a subject having primary sclerosing cholangitis (PSC) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 7 days after the first dose is administered to the subject, and the third dose is administered to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressingNK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0142] Also provided herein is a method of treating primary sclerosing cholangitis (PSC) the method comprising administering to a subject having primary sclerosing cholangitis (PSC) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0143] Also provided herein is a method of treating primary sclerosing cholangitis (PSC), the method comprising administering to a subject having primary sclerosing cholangitis (PSC)a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0144] Also provided herein is a method of treating systemic lupus erythematosus (SLE), the method comprising administering to a subject having SLE a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle,wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR- expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR- expressing NK cells.

[0145] Also provided herein is a method of treating lupus nephritis (LN), the method comprising administering to a subject having LN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8 alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subjectabout 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0146] Also provided herein is a method of treating chronic inflammatory demyelinating polyneuropathy (CIDP), the method comprising administering to a subject having CIDP a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses ofthe dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0147] Also provided herein is a method of treating IgA nephropathy (IgAN), the method comprising administering to a subject having IgAN a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that hinds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In someembodiments, each of the first, second, and third doses of the dosing cycle comprises between about1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 10’ CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0148] Also provided herein is a method of treating ankylosing spondylitis (AS) the method comprising administering to a subject having ankylosing spondylitis (AS), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR- expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressingNK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0149] Also provided herein is a method of treating autoimmune hepatitis (AIH) the method comprising administering to a subject having autoimmune hepatitis (AIH), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CDSalpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR- expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In someembodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0150] Also provided herein is a method of treating chronic graft-versus-host-disease (cGvHD) the method comprising administering to a subject having chronic graft-versus-host- disease (cGvHD), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x 10'° CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0151] Also provided herein is a method of treating cold agglutinin disease (CAD) the method comprising administering to a subject having cold agglutinin disease (CAD), a compositioncomprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR- expressing NK cells or about 2.5 x IO9CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x IO9CAR-expressing NK cells, about 1.5 x IO9CAR-expressing NK cells, about 2 x IO9CAR-expressing NK cells, or about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x IO8CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0152] Also provided herein is a method of treating IgG4-related disease (IgG4-RD) the method comprising administering to a subject having IgG4-related disease (IgG4-RD), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the aminoacid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and fiv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x IO9CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x IO9CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x IO8CAR- expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x IO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x IO9CAR-expressing NK cells.

[0153] Also provided herein is a method of treating primary biliary cholangitis (PBC)the method comprising administering to a subject having primary biliary cholangitis (PBC), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimencomprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR-expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR- expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0154] Also provided herein is a method of treating primary sclerosing cholangitis (PSC) the method comprising administering to a subject having primary sclerosing cholangitis (PSC), a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR- expressing NK cells; and (iv) the second dose is administered to the subject about 3 days after thefirst dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0155] In some embodiments, the NK cells genetically engineered to express a CAR also express a membrane-bound interleukin- 15 (mbIL15). In some embodiments, the mbIL15 comprises the amino acid sequence set forth in SEQ ID NO:23. In some embodiments, the mbIL15 comprises the amino acid sequence set forth in SEQ ID NO:40. In some embodiments, the CAR and the mbIL15 are bicistronically encoded by the same nucleic acid molecule. In some embodiments, the nucleic acid sequences encoding the CAR and the mbIL15 are separated by a nucleic acid sequence encoding a T2A peptide. In some embodiments, the T2A peptide comprises the amino acid sequence set forth in SEQ ID NO:20.

[0156] In some embodiments, the method reduces B cells in the subject. In some embodiments, the method reduces B cells in the subject by at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, or at least about 99%. In some embodiments, the method reduces B cells in the subject by at least about 70%. In some embodiments, the method reduces B cells in the subject by at least about 75%. In some embodiments, the method reduces B cells in the subject by at least about 80%. In some embodiments, the method reduces B cells in the subject by at least about 85%. In some embodiments, the method reduces B cells in the subject by at least about 90%. In some embodiments, among a plurality of subjects treated according to the method, the number ofperipheral B cells in the subjects is reduced by an average of at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 70%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 75%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 80%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 85%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 90%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 95%. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 99%.

[0157] In some embodiments, the method reduces B cells in the subject for at least about 30 days, at least about 45 days, at least about 50 days, at least about 60 days, at least about75 days, at least about 80 days, at least about 90 days or at least about 100 days. In some embodiments, the method reduces B cells in the subject for at least about 30 days. In some embodiments, the method reduces B cells in the subject for at least about 45 days. In some embodiments, the method reduces B cells in the subject for at least about 50 days. In some embodiments, the method reduces B cells in the subject for at least about 60 days. In some embodiments, the method reduces B cells in the subject for at least about 75 days. In some embodiments, the method reduces B cells in the subject for at least about 80 days. In some embodiments, the method reduces B cells in the subject for at least about 90 days. In some embodiments, the method reduces B cells in the subject for at least about 100 days. In some embodiments, the method reduces B cells in the subject for about 30 days, about 45 days, about 50 days, about 60 days, about 75 days, about 80 days, about 90 days or about 100 days. In some embodiments, the method reduces B cells in the subject for about 30 days. In some embodiments, the method reduces B cells in the subject for about 45 days. In some embodiments, the method reduces B cells in the subject for about 50 days. In some embodiments, the method reduces B cells in the subject for about 60 days. In some embodiments, the method reduces B cells in the subject for about 75 days. In some embodiments, the method reduces B cells in the subject for about 80 days. In some embodiments, the method reduces B cells in the subject for about 90 days. In some embodiments, the method reduces B cells in the subject for about 100 days. In some embodiments, the B cells are peripheral B cells.

[0158] In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 15 days, at least about 30 days, at least about 50 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 9 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 15 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 30 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 50 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 1 month following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 2 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 3 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 6 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 9 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, the number of peripheral B cells in the subjects is significantly reduced as compared to subjects not treated according to the method. In some embodiments, the number of peripheral B cells in the subjects is significantly reduced as compared to the subjects prior to administration of a lymphodepleting therapy.

[0159] In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 15 days, about 30 days, about 50 days, about 1 month, about 2 months, about 3 months, about 6 months, or about 9 months following a final dose of the composition comprising NK cells geneticallyengineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 15 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 30 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 50 days following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 1 month following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 2 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 3 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 6 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for about 9 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR.

[0160] In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 10 days, within about 15 days, within about 30 days, within about 40 days, within about 50 days or within about 60 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 10 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 15 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 30 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cellsin the subject is significantly reduced within about 40 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 50 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject. In some embodiments, the number of peripheral B cells in the subject is significantly reduced within about 60 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subject.

[0161] In some embodiments, at about 3 months, at about 6 months, at about 9 months, and / or at about 12 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 3 months, at about 6 months, at about 9 months, at about 12 months, at about 15 months, at about 18 months, or at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the peripheral B cells in the subject are naive B cells.

[0162] In some embodiments, at about 3 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 3 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 3 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 3 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0163] In some embodiments, at about 6 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 6 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 6 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 6 months after administration of a final dose of the composition comprisingNK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0164] In some embodiments, at about 9 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 9 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 9 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 9 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0165] In some embodiments, at about 12 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 12 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 12 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 12 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0166] In some embodiments, at about 15 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 15 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 15 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 15 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75 % of the peripheral B cells in the subject are naive B cells.

[0167] In some embodiments, at about 18 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, atleast about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 18 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 18 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 18 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0168] In some embodiments, at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 30% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 40% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50% of the peripheral B cells in the subject are naive B cells. In some embodiments, at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 75% of the peripheral B cells in the subject are naive B cells.

[0169] In some embodiments, the naive B cells are non-class-switched B cells. In some embodiments, non-class-switched B cells are IgM or IgD isotype. In some embodiments, the non-class-switched B cells are IgM isotype. In some embodiments, the non-class-switched cells are IgD isotype.

[0170] In some embodiments, the method reduces the level of an autoantibody in the subject. In some embodiments, the method reduces the level of an autoantibody in the subject by at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 50%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 60%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 70%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of atleast about 80%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 90%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 95%. In some embodiments, among a plurality of subjects treated according to the method, the level of an autoantibody in the subjects is reduced by an average of at least about 99%. In some embodiments, the level of an autoantibody in the subjects is significantly reduced as compared to subjects having the disease or condition and not treated according to the method. In some embodiments, the level of an autoantibody in the subjects is significantly reduced as compared to the subjects prior to administration of the composition comprising NK cells genetically engineered to express a CAR.

[0171] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for reducing B cells in a subject with a B cell-mediated disease, wherein: the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, the B cell-mediated disease is an autoimmune disease. In some embodiments, prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy. In some embodiments, the lymphodepleting therapy does not comprise administration of fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0172] Also provide herein is use of a lymphodepleting therapy for the preparation of a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the lymphodepleting therapy is administered to the subject prior to administration of the composition to the subject; and (ii) the lymphodepleting therapy comprises cyclophosphamide and does not comprise fludarabine.

[0173] Also provide herein is use of a lymphodepleting therapy for the preparation of a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the lymphodepleting therapy is administered to the subject prior to administration of the composition to the subject; and (ii) the lymphodepleting therapy comprises cyclophosphamide and fludarabine.

[0174] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with an autoimmune disease, wherein: the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, prior to administration of the composition comprising NK cells geneticallyengineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy. In some embodiments, the lymphodepleting therapy does not comprise administration of fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0175] In some embodiments, the genetically engineered NK cells are allogeneic to the subject. In some embodiments, the autoimmune disease is a B cell-mediated autoimmune disease. In some embodiments, the autoimmune disease is selected from the group consisting of systemic lupus erythematosus (SLE), lupus nephritis (LN), scleroderma, rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), NMDA / NMDAR encephalitis, transverse myelitis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), myelin oligodendrocyte glycoprotein spectrum disorder (MOGSD), idiopathic inflammatory myopathy (IIM; also known as myositis), Sjogren’s disease, pemphigus vulgaris, bullous pemphigoid (BP), membranous nephropathy (MN), immune thrombocytopenia (ITP), Hashimoto’s disease, Grave’s disease, insulin resistance, type I diabetes, antiphospholipid syndrome, vasculitis, anti-neutrophilic cytoplasmic antibodies (ANCA) vasculitis (AAV), and antisynthetase syndrome (ASSD). In some embodiments, the autoimmune disease is selected from the group consisting of SLE, LN, scleroderma, MG, myositis (also known as IIM), and vasculitis. In some embodiments, the autoimmune disease is SLE. In some embodiments, the autoimmune disease is LN. In some embodiments, the autoimmune disease is scleroderma. In some embodiments, the autoimmune disease is MG. In some embodiments, the autoimmune disease is UM. In some embodiments, the autoimmune disease is vasculitis. In some embodiments, the autoimmune disease is MS. In some embodiments, the autoimmune disease is NMDA / NMDAR encephalitis. In some embodiments, the autoimmune disease is transverse myelitis. In some embodiments, the autoimmune disease is NMOSD. In some embodiments, the autoimmune disease is MOGAD. In some embodiments, the autoimmune disease is MOGSD. In some embodiments, the autoimmune disease is Sjogren’s disease. In some embodiments, the autoimmune disease is pemphigus vulgaris. In some embodiments, the autoimmune disease is BP. In some embodiments, the autoimmune disease is MN. In some embodiments, the autoimmune disease is ITP. In some embodiments, the autoimmune disease is Hasmimoto’s disease. In some embodiments, the autoimmune disease is Grave’s disease. In some embodiments, the autoimmune disease is type 1 diabeteres. In some embodiments, the autoimmune disease is antiphospholipid syndrome.

[0176] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis opticaspectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmune disease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any combination thereof. In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC).

[0177] In some embodiments, the autoimmune disease comprises Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In some embodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0178] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with systemic lupus erythematosus (SLE), wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0179] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with lupus nephritis (LN), wherein the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0180] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 fortreating a subject having an autoimmune disease, wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain.

[0181] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmune disease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any combination thereof. In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC).

[0182] In some embodiments, the autoimmune disease comprises Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In someembodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0183] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with systemic lupus erythematosus (SLE), wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0184] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with lupus nephritis (LN), wherein the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain.

[0185] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having systemic lupus erythematosus (SLE), wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 2 x 109CAR- expressing NK cells; and (iv) the second dose is for administration to the subject about 7 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x 1010CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 xIO9CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0186] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having lupus nephritis (LN), wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 3 x 109CAR-expressing NK cells; and (iv) the second dose is for administration to the subject about 7 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 7 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0187] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having systemic lupus erythematosus (SLE), wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the compositioncomprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2.5 x 109CAR- expressing NK cells; and (iv) the second dose is for administration to the subject about 3 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0188] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having lupus nephritis (LN), wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 36; (b) a transmembrane domain comprising a CD8alpha transmembrane region; and (c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain; (ii) the composition comprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition; (iii) each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells or about 2 x 109CAR-expressing NK cells; and (iv) the second dose is for administration to the subject about 3 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 4 days after the second dose is administered to the subject. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and 1 x IO10CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR-expressing NK cells. In some embodiments, each of the first, second,and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0189] Also provided herein is use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19 to reduce B cells in a subject having a B cell-mediated disease, wherein: (i) the composition comprising the NK cells genetically engineered to express a CAR is for administration to the subject in a dosing regimen comprising a dosing cycle; and (ii) the composition reduces peripheral B cells in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; and / or at least about 75% of repopulating peripheral B cells are non-class-switched B cells. In some embodiments, the composition reduces peripheral B cells in the subject by at least about 90%. In some embodiments, peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle. In some embodiments, at least about 75% of repopulating peripheral B cells are non-class-switched B cells.

[0190] Also provided herein is a kit comprising (i) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19; and (ii) instructions for administering the composition to a subject having a B cell-mediated disease.

[0191] In some embodiments, the B cell-mediated disease is an autoimmune disease.

[0192] Also provided herein is a kit comprising (i) a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19; and (ii) instructions for administering the composition to a subject having an autoimmune disease.

[0193] In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof. In some embodiments, the autoimmune disease comprises chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the autoimmune disease comprises IgA nephropathy (IgAN). In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or anycombination thereof. In some embodiments, the autoimmune disease comprises ankylosing spondylitis (AS). In some embodiments, the autoimmune disease comprises autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease comprises chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease comprises cold agglutinin disease (CAD). In some embodiments, the autoimmune disease comprises IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease comprises primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease comprises primary sclerosing cholangitis (PSC).

[0194] In some embodiments, the autoimmune disease comprises Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is scleritis. In some embodiments, the autoimmune disease is non-infectious scleritis. In some embodiments, the autoimmune disease is uveitis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is MCTD. In some embodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0195] In some embodiments, the genetically engineered NK cells are allogeneic to the subject. In some embodiments the CAR comprises (a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) having a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively; (b) a transmembrane domain; and (c) an intracellular signaling domain. In some embodiments, administering the composition to the subject comprises administration of the composition to the subject in a dosing regimen comprising a dosing cycle. In some embodiments, the dosing cycle comprises a first dose, a second dose, and a third dose of the composition.

[0196] In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4 x 109CAR- expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each of the first, second, and third doses of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0197] In some embodiments, each dose of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and about 1 x IO10CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 5 x 108CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.25 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 1.75 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2 x 109CAR- expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 2.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 3.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4 x I O9CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 4.5 x 109CAR-expressing NK cells. In some embodiments, each dose of the dosing cycle comprises about 5 x 109CAR-expressing NK cells.

[0198] In some embodiments, each dose of the dosing cycle comprises between about 1 x 106CAR-expressing NK cells / kilogram (kg) and about 1 x 108CAR-expressing NK cells / kg. In some embodiments, if the subject weighs less than 50 kilograms, each dose of the dosing cycle comprises between about 1 x 106CAR-expressing NK cells / kg and about 1 x 108CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 1 x 106CAR- expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 2 x106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 3 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 4 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 5 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 6 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 7 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 8 x 106CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 9 x 106CAR- expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 1 x107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 2 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 3 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of thedosing cycle comprises about 4 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 5 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 6 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 7 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 8 x 107CAR- expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 9 x 107CAR-expressing NK cells / kg. In some embodiments, each dose of the dosing cycle comprises about 1 x 108CAR-expressing NK cells / kg.

[0199] In some embodiments, the NK cells genetically engineered to express a CAR are allogeneic to the subject. In some embodiments, the NK cells are obtained from a donor that does not have a B cell-mediated disease. In some embodiments, the NK cells are obtained from a donor that does not have an autoimmune disease. In some embodiments, the NK cells are obtained from a donor that does not have the disease to be treated. In some embodiments, the NK cells are obtained from a donor that does not have SLE. In some embodiments, the NK cells are obtained from a donor that does not have LN.

[0200] In some embodiments, the NK cells are derived from peripheral blood mononuclear cells (PBMCs). In some embodiments, the NK cells are not derived from cord blood. In some embodiments, the NK cells are not derived from induced pluripotent stem cells (iPSCs).

[0201] In some embodiments, the NK cells genetically engineered to express a CD19 CAR also express a CAR that binds to an antigen associated with an autoimmune disease. In some embodiments, the composition further comprises immune cells genetically engineered to express a CAR that binds to an antigen associated with an autoimmune disease. In some embodiments, the antigen is selected from the group consisting of BAFF-R, BCMA, CD20, CD22, CD27, CD28, CD33, CD38, CD45, CD47, CD54, CD56, CD81, CD117, CD138, CD200, FcRH5, GPRC5D, andSLAMF7. In some embodiments, the antigen is BAFF-R. In some embodiments, the antigen isBCMA. In some embodiments, the antigen is CD20. In some embodiments, the antigen is CD22.In some embodiments, the antigen is CD27. In some embodiments, the antigen is CD28. In some embodiments, the antigen is CD38. In some embodiments, the antigen is CD45. In some embodiments, the antigen is CD47. In some embodiments, the antigen is CD54. In some embodiments, the antigen is CD56. In some embodiments, the antigen is CD81. In some embodiments, the antigen is CD117. In some embodiments, the antigen is CD138. In some embodiments, the antigen is CD200. In some embodiments, the antigen is FcRH5. In some embodiments, the antigen is GPRC5D. In some embodiments, the antigen is SLAMF7. In some embodiments, the immune cells comprise NK cells. In some embodiments, the immune cells comprise T cells. In some embodiments, the immune cells comprise NK cells and T cells.

[0202] In some embodiments, the method further comprises administering a lymphodepleting therapy to the subject prior to administration of the composition comprising NKcells genetically engineered to express a CAR. In some embodiments, prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy.

[0203] In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide. In some embodiments, the lymphodepleting therapy does not comprise administration of fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine. In some embodiments, if a subject is cytopenic, the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine. In some embodiments, if a subject is cytopenic, the lymphodepleting therapy consists of cyclophosphamide. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

[0204] Also provided herein is a method of preparing a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, the method comprising administering a lymphodepleting therapy to the subject prior to administration of the composition to the subject, wherein the lymphodepleting therapy consists of cyclophosphamide. In some embodiments, the subject is cytopenic.

[0205] Also provided herein is a method of preparing a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, the method comprising administering a lymphodepleting therapy to the subject prior to administration of the composition to the subject, wherein the lymphodepleting therapy consists of cyclophosphamide and fludarabine.

[0206] Also provided herein is a method of treating or preventing an autoimmune disease, the method comprising administering to a subject having or suspected or having, or determined to be at risk of, or at risk of relapse of, an autoimmune disease, a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain; (ii) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (iii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine.

[0207] Also provided herein is a method of treating or preventing an autoimmune disease, the method comprising administering to a subject having or suspected or having, or determined to be at risk of, or at risk of relapse of, an autoimmune disease, a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor(CAR) that binds to CD19, wherein: (i) the CAR comprises: (a) an extracellular antigen-binding domain; (b) a transmembrane domain; and (c) an intracellular signaling domain; (ii) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and (iii) the lymphodepleting therapy comprises administration of cyclophosphamide fludarabine.

[0208] In some embodiments, the NK cells genetically engineered to express a CAR also express a mbIL15. In some embodiments, the method is a method of treating an autoimmune disease. In some embodiments, the method is a method of preventing an autoimmune disease. In some embodiments, the subject has an autoimmune disease. In some embodiments, the subject has been determined to be at risk of an autoimmune disease. In some embodiments, the subject has been determined to be at risk of relapse of an autoimmune disease. In some embodiments, the genetically engineered NK cells are allogeneic to the subject.

[0209] In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at between about 200 mg / m2 and about 600 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 200 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 300 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 400 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 500 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 600 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide daily for 2-4 days. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide daily for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 500 mg / m2 daily for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 500 mg / m2 daily on each of days -5, -4, and -3.

[0210] In some embodiments, the lymphodepleting therapy comprises administration of a single dose of cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises between about 500 mg / m2 and about 1500 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises about 500 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises about 750 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises about 1000 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises about 1250 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide comprises about 1500 mg / m2 cyclophosphamide. In some embodiments, a single dose of cyclophosphamide is administered about 3 days prior to administration of thecomposition comprising NK cells genetically engineered to express a CAR. In some embodiments, a single dose of about 1000 mg / m2 cyclophosphamide is administered about 3 days prior to administration of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, a single dose of about 1000 mg / m2 cyclophosphamide is administered on day -3.

[0211] In some embodiments, the lymphodepleting therapy comprises administration of fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine at between about 20 mg / m2 and about 40 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine at about 20 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine at about 25 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine at about 30 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine at about 40 mg / m2 daily. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine daily for 2-4 days. In some embodiments, the lymphodepleting therapy comprises administration of fludarabine daily for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of 25 mg / m2 fludarabine daily for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of 25 mg / m2 fludarabine daily on each of 5, 4, and 3 days prior to administration of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, the lymphodepleting therapy comprises administration of 25 mg / m2 fludarabine daily on each of days -5, -4, and -3. In some embodiments, the lymphodepleting therapy comprises administration of 30 mg / m2 fludarabine daily for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of 30 mg / m2 fludarabine daily on each of 5, 4, and 3 days prior to administration of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, the lymphodepleting therapy comprises administration of 30 mg / m2 fludarabine daily on each of days -5, -4, and -3.

[0212] In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 300 mg / m2 daily and fludarabine at about 30 mg / m2 daily, each for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of cyclophosphamide at about 500 mg / m2 daily and fludarabine at about 30 mg / m2 daily, each for 3 days. In some embodiments, the lymphodepleting therapy comprises administration of about 300 mg / m2 of cyclophosphamide and about 30 mg / m2 of fludarabine on each of Days -5, -4, and -3. In some embodiments, the lymphodepleting therapy comprises administration of about 500 mg / m2 of cyclophosphamide and about 30 mg / m2 of fludarabine on each of Days -5, -4, and -3. In some embodiments, the lymphodepleting therapy comprises administration of a single dose of about 1000 mg / m2 cyclophosphamide and three daily doses ofabout 25 mg / m2 fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of a single dose of about 1000 mg / m2 cyclophosphamide about 3 days prior to administration of the composition comprises NK cells genetically engineered to express a CAR and administration of a dose of about 25 mg / m2 fludarabine on each of 5, 4, and 3 days prior to administration of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, the lymphodepleting therapy comprises administration of a single dose of about 1000 mg / m2 cyclophosphamide on day -3 and a dose of about 25 mg / m2 fludarabine on each of days -5, -4, and -3. In some embodiments, the lymphodepleting therapy comprises administration of about 1000 mg / m2 cyclophosphamide, preferably in a single dose, and three daily doses of about 30 mg / m2 fludarabine. In some embodiments, the lymphodepleting therapy comprises administration of about 1000 mg / m2 cyclophosphamide, preferably in a a single dose, about 3 days prior to administration of the composition that comprises NK cells genetically engineered to express a CAR and administration of a dose of about 30 mg / m2 fludarabine on each of 5, 4, and 3 days prior to administration of the composition comprising NK cells genetically engineered to express a CAR. In some embodiments, the lymphodepleting therapy comprises administration of about 1000 mg / m2 cyclophosphamide, preferably in a single dose, on day -3 and a dose of about 30 mg / m2 fludarabine on each of days -5, -4, and -3.

[0213] In some embodiments, the method comprises administering a corticosteroid to the subject before, during, and / or after administration of the lymphodepleting therapy. In some embodiments, the subject is administered a corticosteroid before, during, and / or after administration of the lymphodepleting therapy. In some embodiments, the subject is administered a corticosteroid before administration of the lymphodepleting therapy. In some embodiments, the subject is administered a corticosteroid during administration of the lymphodepleting therapy. In some embodiments, the subject is administered a corticosteroid after administration of the lymphodepleting therapy. In some embodiments, the subject is administered a corticosteroid before, during, and after administration of the lymphodepleting therapy. In some embodiments, the corticosteroid comprises a glucocorticoid. In some embodiments the corticosteroid is or comprises prednisone.

[0214] In some embodiments, the method comprises administering a corticosteroid to the subject before, during, and / or after administration of the composition. In some embodiments, the subject is administered a corticosteroid before, during, and / or after administration of the composition. In some embodiments, the subject is administered a corticosteroid before administration of the composition. In some embodiments, the subject is administered a corticosteroid during administration of the composition. In some embodiments, the subject is administered a corticosteroid after administration of the composition. In some embodiments, the subject is administered a corticosteroid before, during, and after administration of the composition.In some embodiments, the corticosteroid comprises a glucocorticoid. In some embodiments the corticosteroid is or comprises prednisone.

[0215] In some embodiments, the method comprises administering an immunosuppressive agent to the subject before, during, and / or after administration of the lymphodepleting therapy. In some embodiments, the subject is administered an immunosuppressive agent before, during, and / or after administration of the lymphodepleting therapy. In some embodiments, the subject is administered an immunosuppressive agent before administration of the lymphodepleting therapy. In some embodiments, the subject is administered an immunosuppressive agent during administration of the lymphodepleting therapy. In some embodiments, the subject is administered an immunosuppressive agent after administration of the lymphodepleting therapy. In some embodiments, the subject is administered an immunosuppressive agent before, during, and after administration of the lymphodepleting therapy.

[0216] In some embodiments, the method comprises administering an immunosuppressive agent to the subject before, during, and / or after administration of the composition. In some embodiments, the subject is administered an immunosuppressive agent before, during, and / or after administration of the composition. In some embodiments, the subject is administered an immunosuppressive agent before administration of the composition. In some embodiments, the subject is administered an immunosuppressive agent during administration of the composition. In some embodiments, the subject is administered an immunosuppressive agent after administration of the composition. In some embodiments, the subject is administered an immunosuppressive agent before, during, and after administration of the composition.

[0217] In some embodiments, the immunosuppressive agent comprises an antithymocyte globulin (ATG), an inhibitor of mammalian target of rapamycin (mTOR), a calcineurin inhibitor, or any combination thereof. In some embodiments, the immunosuppressive agent is an antithymocyte globulin (ATG). In some embodiments, the immunosuppressive agent is an inhibitor of mammalian target of rapamycin (mTOR). In some embodiments, the immunosuppressive agent is a calcineurin inhibitor (e.g., voclosporin).

[0218] In some embodiments, the subject was diagnosed with the autoimmune disease (e.g., SLE or LN) between at least about 18 weeks and at least about 30 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease (e.g., SLE or LN) between about 18 weeks and about 30 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 18 weeks, at least about 20 weeks, at least about 22 weeks, at least about 24 weeks, at least about 26 weeks, at least about 28 weeks, or at least about 30 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 20 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 21 weeks priorto administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 22 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 23 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 24 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 25 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 26 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 27 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 28 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 29 weeks prior to administration of the composition. In some embodiments, the subject was diagnosed with the autoimmune disease at least about 30 weeks prior to administration of the composition.

[0219] In some embodiments, the subject is a human. In some embodiments, the subject is less than 18 years of age. In some embodiments, the subject is between about 12 years of age and about 18 years of age. In some embodiments, the subject is at least 12 years of age. In some embodiments, the subject is between about 14 years of age and about 18 years of age. In some embodiments, the subject is at least 14 years of age. In some embodiments, the subject is between about 16 years of age and about 18 years of age. In some embodiments, the subject is at least 16 years of age. In some embodiments, the subject is an adult. In some embodiments, the subject is at least 18 years of age. In some embodiments, the subject is between about 18 and 65 years of age. In some embodiments, the subject is between about 18 and 70 years of age. In some embodiments, the subject is between 18 and 75 years of age.

[0220] In some embodiments, the autoimmune disease is relapsed / refractory. In some embodiments, the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for the autoimmune disease. In some embodiments, the subject has relapsed following treatment with a prior line of therapy for the autoimmune disease. In some embodiments, the subject is refractory to a prior line of therapy for the autoimmune disease. In some embodiments, the prior line of therapy comprises at least one or at least two prior lines of therapy. In some embodiments, the prior line of therapy comprises at least one prior line of therapy. In some embodiments, the prior line of therapy comprises at least two prior lines of therapy.

[0221] In some embodiments, the subject does not have lupus nephritis (LN). In some embodiments, the subject has lupus nephritis (LN). In some embodiments, at the time of administration of the composition to the subject, the subject has SLE with active LN. In some embodiments, the LN is refractory LN. In some embodiments, refractory LN is LN that has failedto respond to at least 2 prior lines of therapy. In some embodiments, at the time of administration of the composition to the subject, the subject has active LN.

[0222] In some embodiments, the subject does not have neuropsychiatric systemic lupus erythematosus (NPSLE). In some embodiments, the subject has neuropsychiatric systemic lupus erythematosus (NPSLE). In some embodiments, the subject has SLE without renal involvement.

[0223] In some embodiments, the SLE is relapsed / refractory SLE. In some embodiments, the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for SLE. In some embodiments, the subject has relapsed following treatment with a prior line of therapy for SLE. In some embodiments, the subject is refractory to a prior line of therapy for SLE. In some embodiments, the subject has relapsed following treatment with and is refractory to a prior line of therapy for SLE.

[0224] In some embodiments, the non-infectious scleritis is relapsed / refractory non- infectious scleritis. In some embodiments, the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for non-infectious scleritis. In some embodiments, the subject has relapsed following treatment with a prior line of therapy for non-infectious scleritis. In some embodiments, the subject is refractory to a prior line of therapy for non-infectious scleritis. In some embodiments, the subject has relapsed following treatment with and is refractory to a prior line of therapy for non-infectious scleritis.

[0225] In some embodiments, the non-infectious uveitis is relapsed / refractory non- infectious uveitis. In some embodiments, the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for non-infectious uveitis. In some embodiments, the subject has relapsed following treatment with a prior line of therapy for non-infectious uveitis. In some embodiments, the subject is refractory to a prior line of therapy for non-infectious uveitis. In some embodiments, the subject has relapsed following treatment with and is refractory to a prior line of therapy for non-infectious uveitis.

[0226] In some embodiments, the MCTD is relapsed / refractory MCTD. In some embodiments, the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for MCTD. In some embodiments, the subject has relapsed following treatment with a prior line of therapy for MCTD. In some embodiments, the subject is refractory to a prior line of therapy for MCTD. In some embodiments, the subject has relapsed following treatment with and is refractory to a prior line of therapy for MCTD.

[0227] In some embodiments, the prior line of therapy comprises two, three, or four prior lines of therapy. In some embodiments, the prior line of therapy comprises two prior lines of therapy. In some embodiments, the prior line of therapy comprises three prior lines of therapy. In some embodiments, the prior line of therapy comprises four prior lines of therapy. In someembodiments, the subject has previously received at least two prior lines of therapy for LN. In some embodiments, the subject has previously received at least three prior lines of therapy for LN.

[0228] In some embodiments, the at least two prior lines of therapy for LN comprise an immunosuppressant and / or an immunomodulatory agent. In some embodiments, the at least two prior lines of therapy for LN comprise an immunosuppressant. In some embodiments, the at least two prior lines of therapy for LN comprise an immunomodulatory agent. In some embodiments, the at least two prior lines of therapy for LN comprise an immunosuppressant and an immunomodulatory agent. In some embodiments, the at least three prior lines of therapy for LN comprise an immunosuppressant and / or an immunomodulatory agent. In some embodiments, the at least three prior lines of therapy for LN comprise an immunosuppressant. In some embodiments, the at least three prior lines of therapy for LN comprise an immunomodulatory agent. In some embodiments, the at least three prior lines of therapy for LN comprise an immunosuppressant and an immunomodulatory agent.

[0229] In some embodiments, the subject was treated with a prior line of therapy for at least about two months. In some embodiments, the subject was treated with a prior line of therapy for between about 3 months and about 24 months. In some embodiments, the subject did not achieve a partial response to the prior line of therapy. In some embodiments, the subject did not achieve a complete response to the prior line of therapy.

[0230] In some embodiments, the prior line of therapy comprises a corticosteroid, an immunosuppressive agent, an antimalarial agent, a B cell-targeting agent, hematopoietic stem cell transplant (HSCT), or any combination thereof. In some embodiments, the prior line of therapy comprises a corticosteroid. In some embodiments, the prior line of therapy comprises a glucocorticoid. In some embodiments, the prior line of therapy comprises an antimalarial agent. In some embodiments, the prior line of therapy comprises an immunosuppressive agent. In some embodiments, the prior line of therapy comprises a B cell-targeting agent. In some embodiments, the prior line of therapy comprises hematopoietic stem cell transplant (HSCT). In some embodiments, the prior line of therapy does not comprise HSCT.

[0231] In some embodiments, the subject achieves a clinical response following a dosing cycle. In some embodiments, the subject achieves a complete response (CR) following a dosing cycle. In some embodiments, the subject achieves a primary efficacy renal response (PERR) following a dosing cycle. In some embodiments, the subject achieves a complete renal response (CRR) following a dosing cycle. In some embodiments, the subject achieves clinical remission following a dosing cycle. In some embodiments, the subject achieves a partial response (PR) following a dosing cycle. In some embodiments, the subject achieves a partial renal response (PRR) following a dosing cycle. In some embodiments, the subject achieves a reduction in disease activity following a dosing cycle. In some embodiments, the subject achieves a reduction in the level of anautoantibody following a dosing cycle. In some embodiments, the autoantibody is associated with the autoimmune disease.

[0232] In some embodiments, if the subject exhibits a clinical response to the treatment, the dosing regimen comprises an additional dosing cycle. In some embodiments, if the subject exhibits a partial response to the treatment, the dosing regimen comprises an additional dosing cycle. In some embodiments, if the subject exhibits a complete response to the treatment, the dosing regimen comprises an additional dosing cycle. In some embodiments, if the subject exhibits an initial clinical response to the treatment and subsequently relapses, the dosing regimen comprises an additional dosing cycle. In some embodiments, if the subject exhibits an initial clinical response to the treatment and subsequent disease progression, the dosing regimen comprises an additional dosing cycle. In some embodiments, the dosing regimen comprises two, three, four, or five dosing cycles. In some embodiments, the dosing regimen consists of two, three, four, or five dosing cycles. In some embodiments, the dosing regimen consists of two dosing cycles. In some embodiments, the dosing regimen consists of three dosing cycles. In some embodiments, the dosing regimen consists of four dosing cycles. In some embodiments, the dosing regimen consists of five dosing cycles. In some embodiments, the dosing regimen comprises no more than five dosing cycles.

[0233] In some embodiments, the method treats an autoimmune disease. In some embodiments, the method prevents an autoimmune disease. In some embodiments, among a plurality of subjects treated according to the method, the average time between disease flares is reduced as compared to a plurality of subjects having the autoimmune disease and not treated according to the method. In some embodiments, among a plurality of subjects treated according to the method, the average severity of disease flare is reduced as compared to a plurality of subjects having the autoimmune disease and not treated according to the method.

[0234] In some embodiments, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, or at least about 90% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 50% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 60% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 70% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 80% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 90% of subjects treated according to the method exhibit a clinical response. In some embodiments, at least about 95% of subjects treated according to the method exhibit a clinical response. In some embodiments, a clinical response comprises a partial response (PR). In some embodiments, a clinical response comprises a complete response (CR). In some embodiments, aclinical response comprises a partial renal response (PRR). In some embodiments, a clinical response comprises a complete renal response (CRR). In some embodiments, a clinical response comprises a primary efficacy renal response (PERR). In some embodiments, a clinical response comprises a reduction in disease activity. In some embodiments, the reduction is disease activity is assessed by a disease index.

[0235] In some embodiments, the subject is human. In some embodiments, the subject is at least about 12 years of age. In some embodiments, the subject is at least about 14 years of age. In some embodiments, the subject is at least about 16 years of age. In some embodiments, the subject is an adult. In some embodiments, the subject is at least about 18 years of age. In some embodiments, the subject is between about 18 and 70 years of age. In some embodiments, the subject is between about 18 and 75 years of age.BRIEF DESCRIPTION OF THE DRAWINGS

[0236] Figure 1 depicts non-limiting schematics of CD19-directed chimeric antigen receptors (CARs).

[0237] Figures 2A-2G depict non-limiting schematics of a dosing cycle for treating an autoimmune disease (e.g., SLE) with CD19 CAR-expressing NK cells (“CD19 CAR NK cells”).

[0238] Figure 3A depicts the in vitro cytotoxicity of nontransduced (“control”) NK cells and CD19 CAR NK cells against CD19+, CD14+, and CD3+ subpopulations of PBMCs.

[0239] Figure 3B depicts the ex vivo cytotoxicity of nontransduced (“control”) NK cells and CD19 CAR NK cells against CD19+ B cells from donors with systemic lupus erythematosus (n=3), scleroderma (n=3), myositis (n=3), myasthenia gravis (n=l), rheumatoid arthritis (n=3), and multiple sclerosis (n=3).

[0240] Figure 4 depicts the in vitro cytotoxicity of control NK cells, CD19 CAR NK cells, and CD19 CAR-expressing T cells (“CD19 CAR T cells”) against CD19+ target cells (Nalm6 and REH cell lines) during 24 or 72 hours of co-culture.

[0241] Figure 5 depicts cytokine levels from control NK cells, CD 19 CAR NK cells, and CD19 CAR T cells following 24-hour co-culture with Nalm-6 or REH target cells at a 1 : 1 E:T ratio (from left to right: control NK cells, CD19 CAR NK cells, CD19 CAR T cells).

[0242] Figure 6A depicts tumor burden (left) and body weight (right) in a murine CD 19-positive xenograft Nalm6 tumor model following treatment with vehicle, control NK cells, or CD 19 CAR NK cells.

[0243] Figure 6B depicts tumor burden in a murine CD19-positive xenograft Raji tumor model following treatment with vehicle or CD19 CAR NK cells.

[0244] Figure 6C depicts trafficking of the CD 19 CAR NK cells into various tissues of the murine CD19-positive xenograft Raji tumor model 20 days after treatment with vehicle or CD19 CAR NK cells.

[0245] Figure 6D depicts trafficking of the CD 19 CAR NK cells into various tissues of non-tumor bearing mice following treatment with vehicle or CD19 CAR NK cells.

[0246] Figure 6E depicts trafficking of the CD 19 CAR NK cells into various tissues of the murine CD 19-positive xenograft Raji tumor model 4 hours after treatment with vehicle or CD19 CAR NK cells.

[0247] Figure 7A depicts the peak concentration (Cmax) of interleukin 15 (IL 15) vs. the Cmax of CD 19 CAR NK cells in subjects with CD 19+ B cell malignancies who were treated with CD19 CAR NK cells in accordance with a non-limiting dosing regimen.

[0248] Figure 7B depicts the average IL15 Cmax in subjects achieving complete response (CR), partial response (PR), or stable or progressive disease (SD / PD) in subjects with CD 19+ B cell malignancies who were treated with CD 19 CAR NK cells in accordance with a nonlimiting dosing regimen.

[0249] Figure 7C depicts the number of CD 19+ cells per microliter (uL) of whole blood in NHL subjects who were treated with CD19 CAR NK cells on Days 0, 7, and 14 in accordance with a non-limiting dosing regimen (each line represents a different subject).

[0250] Figure 7D shows the absolute number of B cells per 800 uL whole blood in NHL subjects at baseline (C1 D-5) and at the indicated days of one or more dosing cycles with CD19 CAR NK cells (Cl: first dosing cycle; C2: second dosing cycle; C3: third dosing cycle; C4: fourth dosing cycle; EOT: end of treatment; FUP1: follow-up one; FUP2: follow-up two; FUP3: followup three; FUP4: follow-up four).

[0251] Figure 7E shows the absolute number of CD 19+ cells per uL whole blood in NHL subjects at the indicated days after treatment with CD19 CAR NK cells.

[0252] Figure 8A shows B cell receptor (BCR) heavy chain isotypes in a representative NHL subject before lymphodepletion (baseline; BL) and at about 6, 9, 12, 15, 18 and 21 months, as assessed by mRNA sequencing (n=l).

[0253] Figure 8B shows B cell receptor (BCR) heavy chain isotypes in NHL subjects at FUP1, as assessed by mRNA sequencing (n=5).

[0254] Figure 8C shows the percentage of B cell subtypes in NHL subjects at FUP1, as assessed by transcriptomic analysis (n=5).

[0255] Figure 9 shows the concentration of CD19 CAR NK cells in two subjects with CD 19+ B cell malignancies who were administered a lymphodepleting therapy of cyclophosphamide and fludarabine (cy / flu) prior to a first dosing cycle and a lymphodepleting therapy of cyclophosphamide only (cy) prior to a second dosing cycle.DETAILED DESCRIPTION

[0256] Provided are methods and uses of genetically engineered immune cells and / or compositions thereof for the treatment or inhibition of an autoimmune disease in a subject. Also provided are methods and uses of genetically engineered immune cells and / or compositions thereof, for the prevention of an autoimmune disease, in a subject suspected of having, or determined to be at risk for, an autoimmune disease. In particular embodiments of any of the provided methods, natural killer (NK) cells are genetically engineered to express a chimeric antigen receptor (CAR) that is directed against CD19.

[0257] In some aspects, the autoimmune disease is a B cell-, T cell-, and / or plasma cell-mediated disease. In some aspects, the autoimmune disease is a B cell-mediated disease. For example, in some aspects, the autoimmune disease is systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and / or multiple sclerosis (MS). In some aspects, the autoimmune disease is acquired immunodeficiency syndrome (AIDS), Addison’s disease, alopecia areata, vasculitis (e.g., anti-neutrophilic cytoplasmic antibodies (ANCA) vasculitis), antiphospholipid syndrome, antisynthetase syndrome, atherosclerosis, bullous pemphigoid (BP), celiac disease, chronic inflammatory demyelinating polyneuropathy (CIDP), Graves’ disease, Guillain-Barre syndrome, Hashimoto thyroiditis, immune thrombocytopenia (ITP), inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis, insulin resistance, membranous nephropathy (MN), myasthenia gravis (MG), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), myelin oligodendrocyte glycoprotein spectrum disorder (MOGSD), myocardial aneurysm, myocardial infarction, IIM (including anti-synthetase syndrome, dermatomyositis, juvenile myositis, necrotizing myopathy, polymyositis, and sporadic inclusion body myositis), neuromyelitis optica spectrum disorder (NMOSD), NMDA / NMDAR encephalitis, pemphigus vulgaris, pernicious anemia, psoriasis, psoriatic arthritis, reactive arthritis, scleroderma (e.g, localized or systemic scleroderma), Sjogren’s disease, transverse myelitis, and / or Type I diabetes.

[0258] In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA), autoimmune encephalitis, chronic inflammatory demyelinating polyneuropathy (CIDP), primary progresssive MS (PPMS), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, ankylosing spondylitis, bullous pemphigoid (BP), primary membranous nephropathy (pMN), IgA nephropathy (IgAN; also known as Berger’s Disease), autoimmune hepatitis (AIH), chronic graft-versus host diseases (cGvHD), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), cold agglutinin disease (CAD) and / or IgG4- related disease (IgG4-RD).

[0259] In some embodiments, the autoimmune disease is chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), coldagglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, and / or warm autoimmune hemolytic anemia (wAIHA).

[0260] In some embodiments, the autoimmune disease is ankylosing spondylitis (AS), autoimmune hepatitis (AIH), chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and / or warm autoimmune hemolytic anemia (wAIHA). In some embodiments, the autoimmune disease is ankylosing spondylitis (AS). In some embodiments, the autoimmune disease is autoimmune hepatitis (AIH). In some embodiments, the autoimmune disease is chronic graft-versus-host-disease (cGvHD). In some embodiments, the autoimmune disease is cold agglutinin disease (CAD). In some embodiments, the autoimmune disease is IgG4-related disease (IgG4-RD). In some embodiments, the autoimmune disease is primary biliary cholangitis (PBC). In some embodiments, the autoimmune disease is primary sclerosing cholangitis (PSC). In some embodiments, the autoimmune disease is warm autoimmune hemolytic anemia (wAIHA).

[0261] In some embodiments, the autoimmune disease is Evans syndrome, autoimmune podocytopathies, scleritis, uveitis, mixed connective tissue disease (MCTD), juvenile dermatomyositis, primary systemic Sjogren’s disease, or any combination thereof. In some embodiments, the autoimmune disease is Evans syndrome. In some embodiments, the autoimmune disease is an autoimmune podocytopathy. In some embodiments, the autoimmune disease is non- infectious scleritis. In some embodiments, the autoimmune disease is non-infectious uveitis. In some embodiments, the autoimmune disease is mixed connective tissue disease (MCTD). In some embodiments, the autoimmune disease is juvenile dermatomyositis. In some embodiments, the autoimmune disease is primary systemic Sjogren’s disease.

[0262] In some embodiments, the methods and uses include administering to a subject having a B cell-mediated disease (e.g., an autoimmune disease) NK cells genetically engineered to express a recombinant receptor (e.g., a CAR) that binds to an antigen (e.g., CD19) expressed by, associated with, and / or specific to B cells (e.g., CD19). Thus, in some embodiments, the methods and uses include administering to a subject having an autoimmune disease, NK cells genetically engineered to express a recombinant receptor (e.g., a CAR) that binds to an antigen (e.g., CD19) expressed by, associated with, and / or specific to cells (e.g., B cells) involved in pathogenesis of the autoimmune disease. The NK cells are generally administered in a composition formulated for administration; the methods generally involve administering the CAR-expressing NK cells as part of a dosing cycle. In some aspects, a dosing cycle comprises multiple (e.g., three) doses of the genetically engineered NK cells. In some aspects, the subject is administered a lymphodepleting therapy prior to administration of the genetically engineered NK cells. Where a subject isadministered more than one dosing cycle, the subject may be administered the lymphodepleting therapy prior to administration of each dosing cycle.

[0263] Without wishing to be bound by theory, it is contemplated that the methods and uses described herein provide or achieve improved response and / or more durable response or efficacy and / or a reduced risk of toxicity or other side effects, including as compared to alternative methods for treating such autoimmune disease. For example, and as described further below, it is contemplated that the methods provided herein are advantageous by virtue of producing an increased and / or a more durable response as compared to other methods such as B cell-targeting agents (e.g., anti-BAFF, anti-CD19, anti-CD20 antibodies, and / or anti-CD22 antibodies). Also, without wishing to be bound by theory, it is contemplated that the provided methods may be advantageous by having reduced risk of toxicity and / or increased ability to retreat as compared to alternative methods, such as CAR T cell therapies.

[0264] CD 19 is a glycoprotein expressed at high levels by B cells throughout all stages of B-cell differentiation (Jin et al., Cell Mol Immunol (2020) 18: 1896-1093). Further, CD19 is not expressed on hematopoietic stem cells or on any normal tissue apart from those of the B-cell lineage. B cells are thought to play a central role in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), SLE, warm autoimmune hemolytic anemia (wAIHA), autoimmune encephalitis, chronic inflammatory demyelinating polyneuropathy (CIDP), primary progresssive MS (PPMS), systemic sclerosis (SSc), ankylosing spondylitis, bullous pemphigoid, primary membranous nephropathy (pMN), IgA Nephropathy (IgAN; also known as Berger’s Disease), autoimmune hepatitis (AIH), ANCA-associated vasculitis (AAV), chronic Graft-versus host Diseases (cGvHD), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), cold agglutinin disease (CAD) and / or IgG4-related disease (IgG4-RD).

[0265] SLE is considered an incurable disease, characterized by a loss of selftolerance with autoantibody production, cellular-tissue infiltration, and end-organ damage that can lead to serious organ complications and even death (Doglio et al., J Allergy Clin Immunol (2022) 150(6): 1289-1301). In particular, hyperactivation of autoreactive B cells is observed in SLE pathogenesis, where it induces plasma cells to produce large amounts of autoantibodies that subsequently circulate and form immune complexes with encountered self-antigens and complement. These immune complexes may then be deposited in small vessels or distal sites, where they can eventually cause organ destruction or dysfunction. See Jin et al. (2020). Among the most significant manifestations of SLE is lupus nephritis (LN). Multiple mechanisms contribute to renal damage in LN, and nephrotic-range proteinuria is found in up to 50% of cases (Parikh et al., Am J Kidney Dis. (2020) 76(2) :265-81 ) . LN is a major risk factor for morbidity and mortality and affects over half of patients with SLE within 10 years. LN leads to end stage renal disease (ESRD) in 10% of patients and corresponds to a 12% mortality (Almaani et al., Clin J Am Soc Nephrol (2017) 12(5) :825-35; Hahn et al., Arthritis Care Res (2012) 64(6) :797-808). In some cases, clinical activityor response is measured in a subject with LN by assessment of primary efficacy renal response (PERR) (Furieet aL, Engl J Med (2020) 383:1117-28), complete renal response (CRR) and partial renal response (PRR) per European Alliance of Associations for Rheumatology (EULAR)ZEuropean Renal Association-European Dialysis and Transplantation Association (ERA- EDTA) criteria (Bertsias et aL, Ann Rheum Dis (2012) 71(11): 1771-82) over time. Other response measures include Assessment of Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) remission over time, change from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAL2K), change from baseline in titer of anti- double-stranded DNA (anti-dsDNA) antibodies, ANA, anti-Smith antibodies, and complement levels (C3, C4, CH50) over time, and changes in serum and urine levels of cytokines subject as interferon- alpha (IFNa) over time.L00266J B-cell depletion strategies, in addition to nonsteroidal anti-inflammatory drugs (NSAIDS), antimalarial drugs, glucocorticoids, and immunosuppression, have been investigated for treatment of SLE. B cell-targeting agents such as anti-BAFF antibodies (e.g., belimumab) were found to only partially deplete B cells in SLE patients. Other BAFF blocking agents, as well as the anti-CD20 antibody rituximab, have yielded negative or mixed results in clinical trials. See Jin et al. (2020). For example, several studies have shown that memory B cells can escape depletion by rituximab, whereas rituximab-treated patients with complete B cell depletion have better responses than those with only partial depletion (Schett et al., Lancet (2023) S0140-6736(23)01126-1).

[0267] Options for patients who have treatment refractory SLE are limited. Hematopoietic cell transplantation (HCT) has also been explored. Unfortunately, this approach has had inconsistent success and comes with potential for considerable toxicity (de Silva et al., Allergy Asthma Clin Immunol (2019) 15:59). Autologous HCT can induce remission in some patients, but the treatment-related mortality exceeds 10% in some studies from complications such as bleeding and infection (Jayne et al., Lupus. (2004) 13(3): 168-76). Because autologous HCT may be beneficial for selected patients, but not for others, allogeneic HCT has also been evaluated. While potentially increasing disease control, allogeneic HCT has potential for even higher treatment- related mortality, with some reports as high as 20% at two years (Daikeler et aL, Bone Marrow Transplant (2009) 44(l):27-33). In summary, there is an urgent need for new therapies with the potential to limit toxicity for patients with systemic autoimmune diseases such as SLE, especially those with severe disease and those with LN.

[0268] Though T cells are widely considered to be major contributors to inflammatory demyelination in multiple sclerosis (MS), growing evidence suggests a significant role for B cells in disease pathogenesis. Both antibody-dependent and independent mechanisms are thought to underlie B-cell mediated central nervous system (CNS) injury in MS. B cell actions may contribute to both MS relapses and disease progression. Primary progressive MS (PPMS), which affects 10- 15% of MS patients, has been a notoriously difficult form of MS to recognize and to treat.Rituximab was tested in PPMS patients in a Phase 2 / 3 trial but failed to meet the primary endpoint (Comi et al., Anna!. Neurol. (2021) 89(1): 13-23). Another anti-CD20 antibody, ocrelizumab, is the first and only approved treatment for PPMS and recommended as first-line therapy by the ECTRIMS-EAN (European Committee for Treatment and Research in Multiple Sclerosis- European Academy of Neurology; Montalban et al., Eur J Neurol. (2018) 25(2):215-37) guidelines. Despite this, the need for more effective therapies in MS, including PPMS, remains.

[0269] Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease marked by persistent symmetric polyarthritis (synovitis) affecting primarily small joints. Significant extra- articular involvement may also occur in organs such as the skin, heart, lungs, and eyes (Muzes and Sipos, Cells (2023) 12(11 ): 1534). A prominent participation of B cells in RA has been appreciated since the discovery of rheumatoid factor (RF) and has been re-highlighted over the past several years; RF and anti-cyclic-citrillunated peptide (anti-CCP) autoantibodies are well-established indicators of disease and disease severity. Initially based on the idea that RF-producing B cells could perpetuate themselves and induce production of TNF, B cell depletion was hypothesized have a beneficial impact in patients with RA. Transient B cell depletion with rituximab, which is approved from TNF-refractory RA, can ameliorate disease for a prolonged period but typically not indefinitely (Marston et al., Curr. Opin. Rheumatol. (2010) 22(2):307- 15). Thus, as some patients do not adequately respond to rituximab treatment, additional therapeutic strategies for treating RA, including TNF refractory RA, are needed.

[0270] B cells have been implicated in a number of other autoimmune diseases, including scleroderma (Kraaij and van Laar, Biologies (2008) 2(3):389-95), myositis (Oddis and Aggarwal, Nat. Rev. Rheumatol. (2018) 14:279-89), myasthenia gravis (MG; Wu et al., Front. Neurol. (2020) 11: 593431), and vasculitis (Merino- Vico et al., Int J Mol Sci. (2022) 23(1): 387).

[0271] Scleroderma is a rare and chronic, autoimmune connective tissue disorder that is primarily characterized by thickening and hardening of the skin and other tissues. The two primary types of scleroderma are systemic scleroderma (also known as systemic sclerosis; SSc) and localized scleroderma. In systemic scleroderma, internal organs such as the digestive tract, heart, lungs, and kidneys may be affected. Depending on how systemic scleroderma manifests, treatment can include immunosuppressive drugs, cyclophosphamide, mycophenolate mofetil, calcium channel blocks (for Raynaud’s phenomenon), prokinetic agents and proton pump inhibitors (for esophageal involvement), ACE inhibitors (for renal involvement), and corticosteroids. The CD20 monoclonal antibody (mAb) rituximab has been evaluated in several clinical studies and is used in practice for the management of cutaneous and pulmonary manifestations of SSc but is not approved for this indication. Limitations of rituximab include its action in triggering B cell activating factor (BAFF) secretion, which perpetuates autoreactive B cells, and failure to target autoreactive long- lived plasma cells (Benfaremo & Gabrielli, 2019; Ehrenstein & Wing, 2016). Autologous CD19- CAR T cell therapy was evaluated in four subjects with severe refractory SSc (Muller et al., N EnglJ Med (2024) 390(8):687-700). The treatment was generally well-tolerated, and the three subjects with > 6 months of follow-up data had decrease in EUSTAR and MRSS scores. In localized scleroderma, the skin is the main organ system involved and muscles and bones may or may not be affected. There are two main forms of localized scleroderma: morphea and linear scleroderma. Morphea is the most common form and presents as a single or multiple plaques, whereas linear scleroderma presents as thickened and indurated skin bands most often on the face or extremities. Different clinical forms of localized scleroderma can coexist in the same patient. Treatments for localized scleroderma can include systemic or topical steroids (e.g., corticosteroids), methotrexate, and phototherapy. There is no curative treatment for scleroderma, such that treatment is designed to relieve symptoms and slow disease progression. The use of different immunosuppressive drugs remains disappointing. (Odonwodo A, Badri T, Hariz A. Scleroderma. [Updated 2022 Aug 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from ncbi.nlm.nih.gov / books / NBK537335 / ).

[0272] Idiopathic inflammatory myopathies (DM, also known as myositis) are heterogenous and rare, and only a few large treatment trial results are available to guide clinicians. A common feature of myositis is chronic inflammation of skeletal muscle, leading to muscle weakness, though other organs such as skin, joints, lungs, gastrointestinal tract, and heart are frequently affected as well. Myositis can be subclassified into anti-synthetase syndrome, polymyositis, dermatomyositis (e.g., juvenile dermatomyositis), inclusion body myositis, and immune-mediated necrotizing myopathy (Lundberg et al., Nat. Rev. Rheumatol. (2018) 14:269- 78). Conventional therapies for myositis include glucocorticoids and immunosuppressive agents, but biological therapies are increasingly being used. Treatment of myositis with rituximab has yielded mixed results, with the primary end point in the largest clinical trial not being met, despite most patients meeting the definition of improvement (DOI) by the end of the trial (Oddis and Aggarwal 2018).

[0273] Myasthenia gravis (MG) is a T cell-dependent, B-cell mediated chronic autoimmune disease caused by antibodies against the AChR, MuSK, or low-density LRP4 expressed in postsynaptic muscle cells, which manifests in muscle weakness and fatigue. About 80% of patients with MG show anti-AChR antibody positivity, and about 40% of the anti-AChR antibody-negative patients show anti-MuSK antibody positivity. The presence of anti-LRP4 autoantibodies can be detected among patients outside the previous groups (Miizes and Sipos Cells (2023) 12(11): 1534). Conventional treatment options, including symptomatic treatments and general immunosuppression, can help, though durable remission remains improbable, and chronic treatment with high doses of non-specific immunosuppressive drugs is usually necessary to maintain disease remission (Wu 2020). More recent treatment approaches include B cell-targeting therapies such as monoclonal antibodies and proteasome-targeting inhibitors. However, thereremains an unmet need for effective treatments, particularly for patients with refractory disease (Huda, Front. Immunol. (2020) 11:240).

[0274] Vasculitis is classified primarily by the predominant size of the vessels involved, and the 2012 Chapel Hill Consensus Conference (CHCC) represents a widely used nomenclature and classification system for vasculitis (Jennette et al., Arthritis Rheum. (2013) 65 : 1- 11). Specifically, vasculitis is subdivided into large- vessel, medium-vessel, and small-vessel vasculitis. Large-vessel vasculitis includes Takayasu arteritis (TAK) and giant cell arteritis (GCA), which primarily affect the aorta and its major branches. Medium-vessel vasculitis includes polyarteritis nodosa (PAN) and Kawasaki disease, which typically affect medium- and small-sized arteries. Small-vessel vasculitis includes ANCA-associated vasculitis (AAV), which is a systemic autoimmune disease that affects small sized blood vessels and can lead to serious complications in the lungs and kidneys (Merino-Vico 2022). AAV encompasses three major types of vasculitides that have different clinical characteristics, namely granulomatosis with polyangiitis (GPA, previously referred to as Wegener’s granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) (Jennette and Falk, Semin. Immunopathol. (2014) 36:327-38). The prominent presence of ANCA autoantibodies in this disease implicates B cells in its pathogenesis, as these are the precursors of the ANCA-producing plasma cells (PCs). Further evidence supporting the potential role of B lineage cells in vasculitis are the increased B cell cytokine levels and the dysregulated B cell populations in patients. Confirmation of the contribution of B cells to pathology arose from the beneficial effect of anti-CD20 therapy (i.e., rituximab) in AAV patients. These anti-CD20 antibodies deplete circulating B cells, which results in amelioration of disease. However, not all patients respond completely, and this treatment does not target PCs, which can maintain ANCA production (Merino-Vico 2022).

[0275] Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disorder characterized by premature destruction of erythrocytes. It is caused by activation of complement (C) if autoantibody IgG is present at a higher amount or if subclasses such as IgGl and IgG3 are present. About 95% of patients with wAIHA have an anti-IgG antibody that bind to antigens on Red Blood Cells (RBC) and about 5% of patients with wAIHA have anti-IgA and even less commonly anti-IgM antibodies (Kuter, Hematology Am Soc Hematol Educ Program. (2022) 2022(1): 105-113). The binding of IgG antibody to protein antigens on the RBC surface can be analyzed by a positive Coombs test. Conventional therapies for wAIHA include administration of corticosteroids and / or RBC transfusion. While other treatments like administration of rituximab or immunosuppressive agents like mycophenolate for patients with wAIHA have also been tested ((Barcellini et al., (Blood. (2012) 119( 16):3691-3697) and Howard et al., (Br J Haematol. (2002) 117(3):712-715)), there remains a need for effective treatments given the complications of longterm corticosteroid treatments.

[0276] Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune- mediated polyneuropathy associated with inflammation of nerve roots that leads to a progressive impairment in the sensory function. CIDP is also referred to as chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy. The acute manifestation of CIDP is Guillain-Barre syndrome. About 10% of patients with CIDP have an autoantibody against nodal and / or paranodal proteins (Gogia et aL, (2024) Treasure Island (FL): StatPearls Publishing). Multiple factors contribute to immune mechanisms that target myelin in the peripheral nervous system (Lehmann et al., J Neurol Neurosurg Psychiatry. (2019) 90(9):981-987). While corticosteroids, in addition to Intravenous Immune Globulin (IVIG) and plasma exchange have been used in standard treatment of CIDP, there remains a need for effective therapies given the resistance developed by patients to standard therapies.[00277J IgA Nephropathy (IgAN) also known as Berger’s Disease is an autoimmune kidney disease caused by the accumulation of IgA antibodies on kidneys. While about 90% of IgAN cases are sporadic, a variety of diseases and disorders have been shown to cause secondary IgAN (Lai et al., Nat Rev Dis Primers. (2016) 11; 2: 16001: Rollino et al., J Nephrol. (2016) 29(4):463-8; Abbad et al., Mol Immunol. (2020)121: 1-6). In some embodiments, the subject has IgAN, as defined by Oxford classification that employs a scoring criteria based on mesangial cellularity (M), Endocapillary hypercellularity (E), Segmental sclerosis (S), Interstitial fibrosis / tubular atrophy (T) and Cellular / fibrocellular crescents (C) and assigning a total MEST-C score (Howie et al., Kidney 360. (2023) 4(8) : 1103-1111). The deposition of IgA on the glomerular basement membrane by histological ex...

Claims

WHAT IS CLAIMED:

1. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

2. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises primary membranous nephropathy (pMN).

3. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis.

4. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious uveitis.

5. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises mixed connective tissue disease (MCTD).

6. A method of reducing B cells in a subject having an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

7. A method of reducing B cells in a subject having an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises primary membranous nephropathy (pMN).

8. A method of reducing B cells in a subject having an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious uveitis.

9. A method of reducing B cells in a subject having an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious uveitis.

10. A method of reducing B cells in a subject having an autoimmune disease, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the genetically engineered NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises mixed connective tissue disease (MCTD).

11. The method of any one of claims 1-10, wherein:(i) the method comprises administering a lymphodepleting therapy to the subject prior to administration of the composition comprising NK cells genetically engineered to express a CAR; or(ii) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy.

12. The method of claim 11, wherein the lymphodepleting therapy comprises administration of cyclophosphamide.

13. The method of claim 11, wherein, if the subject is cytopcnic, the lymphodepleting therapy does not comprise administration of fludarabine.

14. The method of claim 11, wherein the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine.

15. The method of any one of claims 1-14, wherein the CAR comprises:(a) an extracellular antigen-binding domain;(b) a transmembrane domain; and(c) an intracellular signaling domain.

16. The method of claim 15, wherein the extracellular antigen-binding domain comprises a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and alight chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively.

17. The method of claim 16, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO:35, and the VL comprises the amino acid sequence set forth in SEQ ID NO:36.

18. The method of claim 15, wherein the extracellular antigen-binding domain is a single-chain variable fragment (scFv) comprising the amino acid sequence set forth in SEQ ID NO:37.

19. The method of claim 15, wherein the transmembrane domain comprises a CD8alpha transmembrane region.

20. The method of claim 15, wherein the transmembrane domain comprises the amino acid sequence set forth in SEQ ID NO:8.

21. The method of claim 15, wherein the intracellular signaling domain comprises an intracellular signaling region of 0X40 and a CD3zeta domain.

22. The method of claim 21, wherein the intracellular signaling region of 0X40 comprises the amino acid sequence set forth in SEQ ID NO: 14.

23. The method of claim 21 , wherein the CD3zeta domain comprises the amino acid sequence set forth in SEQ ID NO: 16.

24. The method of any one of claims 1-23, wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO:38.

25. The method of any one of claims 1-24, wherein the NK cells genetically engineered to express a CAR also express a membrane-bound interleukin- 15 (mbIL15).

26. The method of claim 25, wherein the mbIL15 comprises the amino acid sequence set forth in SEQ ID NO:40.

27. The method of claim 25 or 26, wherein the CAR and the mbIL15 are bicistronically encoded by the same nucleic acid molecule, optionally wherein the nucleic acid sequences encoding the CAR and the mbIL15 are separated by a nucleic acid sequence encoding a T2A peptide.

28. The method of any one of claims 1-27, wherein the NK cells are derived from peripheral blood mononuclear cells (PBMCs).

29. The method of any one of claims 1-28, wherein the composition comprising NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle.

30. The method of claim 29, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition comprising NK cells genetically engineered to express a CAR.

31. The method of claim 30, wherein the second dose is administered to the subject between about 2 days after and about 4 days after the first dose is administered to the subject.

32. The method of claim 31, wherein the third dose is administered to the subject between about 2 days after and about 4 days after the second dose is administered to the subject.

33. The method of claim 30, wherein the first dose is administered on about Day 0 of the dosing cycle, the second dose is administered on about Day 3 of the dosing cycle, and the third dose is administered on about Day 7 of the dosing cycle.

34. The method of claim 30, wherein each dose of the dosing cycle comprises between about 1 x 108CAR-expressing NK cells and about 1 x IO10CAR-expressing NK cells, or between about 3 x 108CAR-expressing NK cells and about 3 x 109CAR-expressing NK cells, each inclusive.

35. The method of claim 30, wherein each dose of the dosing cycle comprises about 3 x 108CAR-expressing NK cells, about 1 x 109CAR-expressing NK cells, or about 1.5 x 109CAR- expressing NK cells.

36. The method of claim 30, wherein each dose of the dosing cycle comprises about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells37. The method of claim 30, wherein:(i) each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-expressing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells; and(ii) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject.

38. The method of claim 30, wherein each dose of the dosing cycle comprises about 3 x 109CAR-expressing NK cells, about 3.5 x 109CAR-expressing NK cells, about 4 x 109CAR-expressing NK cells, about 4.5 x 109CAR-expressing NK cells, or about 5 x 109CAR-expressing NK cells.

39. The method of claim 38, wherein:(i) each of the first, second, and third doses of the dosing cycle comprises about2.5 x 10’ CAR-expressing NK cells, about 3 x 109CAR-expressing NK cells, about 3.5 x 109CAR-expressing NK cells, or about 4 x 109CAR-expressing NK cells; and(ii) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject.

40. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition;(ii) each of the first, second, and third doses of the dosing cycle comprises between about 2.5 x 109CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells;(iii) the autoimmune disease affects the subject’s skin, muscles, kidneys, or any combination thereof.

41. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein:(i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition;(ii) each of the first, second, and third doses of the dosing cycle comprises about 1 x 109CAR-cxprcssing NK cells, about 1.5 x 109CAR-expressing NK cells, about 2 x 109CAR-expressing NK cells, or about 2.5 x 109CAR-expressing NK cells;(iii) the second dose is administered to the subject about 3 days after the first dose is administered to the subject, and the third dose is administered to the subject about 4 days after the second dose is administered to the subject; and(iv) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinatingpolyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

42. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy;(ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and(iii) the autoimmune disease comprises primary membranous nephropathy (pMN).

43. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein:(i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy;(ii) the lymphodepleting therapy comprises administration of cyclophosphamide and does not comprise administration of fludarabine; and(iii) the autoimmune disease comprises non-infectious scleritis.

44. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy;(ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and(iii) the autoimmune disease comprises non-infectious uveitis.

45. A method of treating an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein:(i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy;(ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and(iii) the autoimmune disease comprises mixed connective tissue disease (MCTD).

46. A method of an autoimmune disease in a subject, the method comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and(ii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine; and(iii) the autoimmune disease is selected from the group consisting of non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), TgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft- versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4- RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis(RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

47. The method of any one of claims 11-39 and 42-46, wherein the lymphodepleting therapy comprises administration of cyclophosphamide at between about 500 mg / m2and about 1500 mg / m2, optionally wherein the lymphodepleting therapy comprises administration of a single dose of about 1000 mg / m2cyclophosphamide.

48. The method of any one of claims 11-39 and 42-47, wherein, the lymphodepleting therapy comprises administration of about 1000 mg / m2of cyclophosphamide about three days prior to administration of the composition to the subject.

49. The method of any one of claims 11, 12, 14-39, and 42-48, wherein, the lymphodepleting therapy comprises administration of between about 20 mg / m2and about 30 mg / m2of fludarabine.

50. The method of any one of claims 11, 12, 14-39, and 42-49, wherein, the lymphodepleting therapy comprises administration of about 30 mg / m2of fludarabine.

51. The method of any one of claims 11, 12, 14-39, and 42-49, wherein, the lymphodepleting therapy comprises administration of fludarabine on each of three, four, and five days prior to administration of the composition to the subject.

52. The method of any one of claims 1-51, wherein the subject has relapsed following treatment with and / or is refractory to a prior line of therapy for the autoimmune disease.

53. The method of claim 52, wherein the prior line of therapy comprises two, three, or four prior lines of therapy.

54. The method of claim 52 or 53, wherein the prior line of therapy comprises a corticosteroid, an immunosuppressive agent, an antimalarial agent, a B cell-targeting agent, hematopoietic stem cell transplant (HSCT), or any combination thereof.

55. The method of any one of claims 11-39 and 42-54, wherein the subject is administered a corticosteroid before, during, and / or after administration of (i) the lymphodepleting therapy and / or (ii) the composition, optionally wherein the corticosteroid comprises a glucocorticoid.

56. The method of any one of claims 11-39 and 42-55, wherein the subject is administered an immunosuppressive agent before, during, and / or after administration of the (i) lymphodepleting therapy; and / or (ii) the composition, optionally wherein the immunosuppressive agent comprises an antithymocyte globulin (ATG), an inhibitor of mammalian target of rapamycin (mTOR), a calcineurin inhibitor, or any combination thereof.

57. The method of any one of claims 1-56, wherein the subject does not have CNS lupus.

58. The method of claim 29, wherein the dosing regimen comprises or consists of two, three, four, or five dosing cycles.

59. A method of preparing a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, the method comprising administering a lymphodepleting therapy to a subject having an autoimmune disease prior to administration of the composition to the subject, wherein:(i) the lymphodepleting therapy comprises cyclophosphamide; and(ii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

60. The method of claim 59, wherein the lymphodepleting therapy comprises cyclophosphamide at between about 500 mg / m2and about 1500 mg / m2, optionally wherein the lymphodepleting therapy comprises a single dose of about 1000 mg / m2cyclophosphamide.

61. The method of claim 59 or claim 60, wherein the lymphodepleting therapy comprises a single dose of about 1000 mg / m2cyclophosphamide about three days before administration of the composition.

62. The method of any one of claims 59-61, wherein the lymphodepleting therapy comprises a dose of between about 20 mg / m2and about 40 mg / m2fludarabine on each of three, four, and five days before administration, optionally wherein the dose is 30 mg / m2fludarabine.

63. The method of any one of claims 1-62, wherein the NK cells genetically engineered to express a CAR that binds to CD19 also express a membrane -bound interleukin- 15 (mbIL15).

64. The method of any one of claims 1-63, wherein, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is reduced by an average of at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%, optionally as compared to subjects not treated according to the method.

65. A method of reducing B cells in a subject having an autoimmune disease comprising administering to a subject having an autoimmune disease a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein:(i) the NK cells are allogeneic to the subject;(ii) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle; and(iii) the method reduces peripheral B cells in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; and / or at least about 75% of repopulating peripheral B cells are non-class-switched B cells.

66. The method of claim 65, wherein the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

67. A method of reducing B cells in a subject having an autoimmune disease comprising administering to a subject having an autoimmune disease a composition comprising natural killer(NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19, wherein:(i) the composition comprising the NK cells genetically engineered to express a CAR is administered to the subject in a dosing regimen comprising a dosing cycle;(ii) the method reduces peripheral B cells in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; and / or at least about 75% of repopulating peripheral B cells are non-class-switched B cells; and(iii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

68. The method of any one of claims 1-67, wherein, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced within about 10 days, within about 15 days, within about 30 days, within about 45 days, within about 50 days or within about 60 days after administration of a first dose of the composition comprising NK cells genetically engineered to express a CAR to the subjects, optionally as compared to subjects not treated according to the method.

69. The method of any one of claims 1-68, wherein, among a plurality of subjects treated according to the method, the number of peripheral B cells in the subjects is significantly reduced for at least about 15 days, at least about 30 days, at least about 50 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 9 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR, optionally as compared to subjects not treated according to the method.

70. The method of any one of claims 1-69, wherein, at about 3 months, at about 6 months, at about 9 months, at about 12 months, at about 15 months, at about 18 months and / or at about 21 months after administration of a final dose of the composition comprising NK cells genetically engineered to express a CAR to the subject, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the peripheral B cells in the subject are naive B cells.

71. The method of claim 70, wherein the naive B cells are non-class-switched, optionally wherein the naive B cells are IgM or IgD isotype.

72. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

73. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19 for reducing B cells in a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

74. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises primary membranous nephropathy (pMN).

75. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious scleritis.

76. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises non-infectious uveitis.

77. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the NK cells are allogeneic to the subject; and(ii) the autoimmune disease comprises mixed connective tissue disease (MCTD).

78. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for reducing peripheral B cells in a subject having a B cell-mediated disease wherein:(i) the NK cells are allogeneic to the subject;(ii) the composition comprising the NK cells genetically engineered to express a CAR is for administration to the subject in a dosing regimen comprising a dosing cycle; and(iii) peripheral B cells are reduced in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; or at least about 75% of repopulating peripheral B cells are non-class-switched B cells.

79. The use of claim 78, wherein the B-cell mediated disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis(PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

80. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19 for reducing peripheral B cells in a subject having a B cell-mediated disease wherein:(i) the composition comprising the NK cells genetically engineered to express a CAR is for administration to the subject in a dosing regimen comprising a dosing cycle;(ii) peripheral B cells are reduced in the subject by at least about 90%; peripheral B cells are significantly reduced in the subject for the duration of the dosing cycle; or at least about 75% of repopulating peripheral B cells are non-class-switched B cells,(iii) wherein B-cell mediated disease comprises non-infectious scleritis, non- infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host- disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

81. Use of a lymphodepleting therapy for the preparation of a subject having an autoimmune disease for treatment with a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19, wherein:(i) the lymphodepleting therapy is administered to the subject prior to administration of the composition to the subject; and(ii) the lymphodepleting therapy comprises cyclophosphamide and fludarabine, wherein the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis(PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

82. The use of any one of claims 72-81, wherein the CAR comprises:(a) an extracellular antigen-binding domain;(b) a transmembrane domain; and(c) an intracellular signaling domain.

83. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating or preventing an autoimmune disease in a subject having or suspected or having, or determined to be at risk of, an autoimmune disease, wherein:(i) the CAR comprises:(a) an extracellular antigen-binding domain;(b) a transmembrane domain; and(c) an intracellular signaling domain,(ii) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and(iii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine, wherein the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (C1DP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

84. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD 19 for reducing B cells in a subject having or suspected or having, or determined to be at risk of, an autoimmune disease, wherein:(i) the CAR comprises:(a) an extracellular antigen-binding domain;(b) a transmembrane domain; and(c) an intracellular signaling domain,(ii) prior to administration of the composition comprising NK cells genetically engineered to express a CAR to the subject, the subject has been administered a lymphodepleting therapy; and(iii) the lymphodepleting therapy comprises administration of cyclophosphamide and fludarabine, wherein the autoimmune disease comprises non-infectious scleritis, non-infectious uveitis, mixed connective tissue disease (MCTD), chronic inflammatory demyelinating polyneuropathy (CIDP), IgA nephropathy (IgAN), ankylosing spondylitis (AS), antiphospholipid syndrome (APS), autoimmune encephalitis (AE), autoimmune hepatitis (AIH), bullous pemphigoid (BP), Crohn’s disease, chronic graft-versus-host-disease (cGvHD), cold agglutinin disease (CAD), IgG4-related disease (IgG4-RD), neuromyelitis optica spectrum disorder (NMOSD), pemphigus vulgaris (PV), primary biliary cholangitis (PBC), primary membranous nephropathy (pMN), primary progressive multiple sclerosis (PPMS), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjogren’s syndrome, warm autoimmune hemolytic anemia (wAIHA), or any combination thereof.

85. The use of any one of claims 82-84, wherein the extracellular antigen-binding domain comprises a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR- 3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively.

86. The use of any one of claims 82-85, wherein the transmembrane domain comprises a CD8alpha transmembrane region.

87. The use of any one of claims 82-86, wherein the intracellular signaling domain comprises an intracellular signaling region of 0X40 and a CD3zeta domain.

88. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject with an autoimmune disease, wherein the CAR comprises:(a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NOS: 24, 25, and 26, respectively; and a light chain variable region (VL) comprising a CDR-1, a CDR-2, and a CDR-3 comprising the amino acid sequences set forth in SEQ ID NO: 27, HT, and SEQ ID NO: 29, respectively;(b) a CD8alpha transmembrane domain; and(c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain.

89. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the CAR comprises:(a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36;(b) a transmembrane domain comprising a CD8alpha transmembrane region; and(c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain;(ii) the composition comprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition;(iii) each of the first, second, and third doses of the dosing cycle comprises between about 1 x 109CAR-expressing NK cells and about 2.5 x 109CAR-expressing NK cells; and(iv) the second dose is for administration to the subject about 3 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 4 days after the second dose is administered to the subject.

90. Use of a composition comprising natural killer (NK) cells genetically engineered to express a chimeric antigen receptor (CAR) that binds to CD19 for treating a subject having an autoimmune disease, wherein:(i) the CAR comprises:(a) an extracellular antigen-binding domain comprising a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 35, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:36;(b) a transmembrane domain comprising a CD8alpha transmembrane region; and(c) an intracellular signaling domain comprising an intracellular signaling region of 0X40 and a CD3zeta domain;(ii) the composition comprising the NK cells genetically engineered to express a CAR is formulated for administration in a dosing regimen comprising a dosing cycle, wherein the dosing cycle comprises a first dose, a second dose, and a third dose of the composition;(iii) each of the first, second, and third doses of the dosing cycle comprises between about 3 x 109CAR-expressing NK cells and about 5 x 109CAR-expressing NK cells;(iv) the second dose is for administration to the subject about 3 days after the first dose is administered to the subject, and the third dose is for administration to the subject about 4 days after the second dose is administered to the subject; and(v) the autoimmune disease affects the skin, muscles, kidneys, or any combination thereof, of the subject.

91. The use of any one of claims 88-90, wherein the autoimmune disease comprises primary membranous nephropathy (pMN).

92. The use of any one of claims 88-90, wherein the autoimmune disease comprises non-infectious scleritis.

93. The use of any one of claims 88-90, wherein the autoimmune disease comprises non-infectious uveitis.

94. The use of any one of claims 88-90, wherein the autoimmune disease comprises mixed connective tissue disease (MCTD).

95. The use of any one of claims 72-94, wherein the genetically engineered NK cells are allogeneic to the subject.

96. The use of any one of claims 72-95, wherein, among a plurality of subjects treated with the composition comprising NK cells genetically engineered to express a CAR, the number of peripheral B cells in the subjects is reduced by an average of at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.

97. The use of any one of claims 72-996, wherein, among a plurality of subjects treated with the composition comprising NK cells genetically engineered to express a CAR, the number of peripheral B cells in the subjects is significantly reduced for at least about 15 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, or at least about 9 months following a final dose of the composition comprising NK cells genetically engineered to express a CAR.

98. The use of any one of claims 81-87 wherein the lymphodepleting therapy comprises cyclophosphamide at between about 500 mg / m2and about 1500 mg / nr, optionally wherein the lymphodepleting therapy comprises a single dose of about 1000 mg / m2cyclopho sphamide .

99. The use of claim 81-87 and 98, wherein the lymphodepleting therapy comprises about 1000 mg / m2of cyclophosphamide about 3 days before administration of the composition.

100. The use of any one of claims 81-87, 98 and 99, wherein, the lymphodepleting therapy comprises administration of between about 20 mg / m2and about 40 mg / m2of fludarabine.

101. The use of any one of claims 81-87 and 98-100, wherein, the lymphodepleting therapy comprises administration of about 30 mg / m2of fludarabine.

102. The use of any one of claims 81-87 and 98-101, wherein, the lymphodepleting therapy comprises administration of fludarabine on each of three, four, and five days prior to administration of the composition to the subject.

103. The use of any one of claims 72-102, wherein the NK cells genetically engineered to express a CAR that binds to CD19 also express a membrane-bound interleukin- 15 (mbIL15).

104. The method of any one of claims 72 to 103, wherein the NK cells genetically engineered to express a CAR that binds to CD 19 are derived from peripheral blood mononuclear cells (PBMCs).

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