Methods and compositions for enhancing the persistence of car expressing tregs in the CNS and other tissues

Abstract

Modified Tregs including DNA constructs encoding (1) chimeric antigen receptor (CAR), (2) at least one of IL-2, IL-2 mutein, or constitutively active STAT5B (STAT5B-CA) or STAT5A (STAT5A-CA), and (3) optionally a "neurodegenerative disease-modifying molecule" (NDMM) or "disease-modifying molecule" (DMM) are described. DNA encoding (1), (2) and optionally (3) is on the same or different constructs; (ii) expression (1), (2) and optionally (3) is controlled by inducible or constitutive promoters; (iii) the described Treg inducibly or constitutively expresses IL-2, IL-2 mutein, or STAT5B-CA or STAT5A-CA, the CAR, and optionally a DMM or NDMM in vivo; and (iv) the Treg persists longer and / or in greater numbers in the CNS and / or spleen compared to Tregs expressing the same CAR without exogenous DNA encoding IL-2, IL-2 mutein or STAT5B-CA or STAT5A-CA. CAR DNA constructs used to produce such modified Tregs and uses thereof for treatment of neurodegenerative diseases are also described.

Description

[0001]METHODS AND COMPOSITIONS FOR ENHANCING THE PERSISTENCE OF CAR EXPRESSING TREGS IN THE CNS AND OTHER TISSUES CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to: U.S. Provisional Application No.: 63 / 651,204, filed on May 23, 2024, entitled “METHODS AND COMPOSITIONS CONTAINING FOR ENHANCING THE PERSISTENCE OF CAR EXPRESSING TREGS IN THE CNS AND OTHER TISSUES”. The contents of the applications are incorporated by reference in their entirety herein. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT The instant application was made with government support under grant numbers NS132666, AG081632, AG067971, NS117895 awarded by the National Institutes of Health. The government has certain rights in the invention. REFERENCE TO SEQUENCE LISTING The contents of the electronic sequence listing (1143252_007813_SL.xml; Size: 313,042 bytes; and Date of Creation: April 25, 2025) is herein incorporated by reference in its entirety. FIELD OF THE ART The present disclosure generally relates to methods, cells and DNA constructs for use in such methods which provide for the enhanced persistence of CAR-expressing Tregs in the CNS and other tissues. The present disclosure specifically relates to CAR expressing Tregs which better retain the phenotype of Tregs and / or which persist for prolonged duration in the CNS and other tissues after being introduced into a subject in need thereof which include a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5A or STAT5B and combinations thereof, wherein such cargo proteins may be expressed along with the CAR or induced as a result of CAR signaling. The present disclosure also relates to methods for producing CAR expressing Tregs which better retain the phenotype of Tregs and which better persist in the CNS by introducing a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5A or STAT5B or combinations of any of the foregoing. The present disclosure further relates to compositions containing such modified Tregs, and methods of use thereof as therapeutics, e.g., for treating and preventing neurodegenerative diseases 145733510.1 and symptoms associated therewith, and / or for slowing the onset of such neurodegenerative diseases such as Alzheimer’s disease and ALS. BACKGROUND Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is one of the primary reasons for memory dysfunction and dementia after 60 years of age. Neuronal dysfunction and death in the frontal cortex and hippocampus, along with microglia-mediated neuroinflammation and formation of aberrant protein aggregates and fibrils are hallmarks of AD. Sporadic and familial forms of AD have an overproduction and / or decreased clearance of extracellular amyloid-beta (Aβ) peptides and intraneuronal tangles of twisted tau protein fibers. Aβ peptides self-oligomerize into small aggregates that can develop into diffuse plaques. Multiple antibodies that bind Aβ in its monomeric, oligomeric, and plaque forms have been created. Neuroinflammation is known to occur in AD, and when associated near Aβ plaques there is a greater neurodegeneration. Data support a conclusion that inflammatory microglia, the resident macrophages of the central nervous system, have a role in neurodegeneration and cognitive decline. Aberrant innate immune responses and altered inflammation are associated with AD and are involved in AD disease in murine models. Data show that inflammation modulators may be beneficial in AD mouse models. One challenge is how to delivery anti-inflammatory therapy that provides multiple mechanisms to the sites of disease. T regulatory cells (Tregs) are a subset of T cells that have inherent anti-inflammatory activity, and Tregs are being investigated as cellular therapies for chronic inflammatory and autoimmune diseases. Tregs have been shown to modulate microglia function. Tregs are found in the CNS under steady state conditions and increase in regions of CNS inflammation. Although the overall role for Tregs in AD and other neurodegenerative diseases is not well understood, many studies support a potential beneficial role for Tregs in AD and other neurodegenerative diseases. CAR cell therapy is a great approach for therapy because cells as drugs can traffic to sites of disease, persist in vivo (when engineered to do so), respond to environmental cues (e.g. antigen) to trigger or limit activities, and delivery multiple therapeutic mechanisms. Recently the use of CAR expressing Tregs for use in therapy, e.g., in the treatment of inflammatory diseases and neuroinflammatory or neurodegenerative diseases such as AD has been reported by the present Applicant as well as by other groups. While CAR expressing Tregs show great promise as therapeutics, a disadvantage is that adoptively transferred CAR expressing Tregs often do not persist, e.g., in the CNS, for prolonged duration thereby reducing the efficacy of CAR Treg therapies. The present disclosure seeks to address this unmet need in the art. 245733510.1 BRIEF SUMMARY An overarching goal of the present disclose is to provide improved therapies which use modified Tregs to, for example, rebalance cerebral immunity, promote Aβ clearance, and limit neuron damage. A key challenge for Treg therapy is that polyclonal Tregs do not target disease- associated antigens and also there is no IL-2 in the CNS to support Treg persistence. Data presented herein show that chimeric antigen receptor (CAR) Tregs targeted to AD-associated antigens that are engineered to persist solve these key problems. In exemplary embodiments the inventors teach the production of modified Tregs which include a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5B, a constitutively active STAT5A, or a combination of any of the foregoing, which better persist in the CNS and which further include a CAR, e.g., one that binds to aggregated amyloid-beta (A-β), which CAR Tregs are triggered at the site of A-β plaques, which is a different therapeutic intent than removal of A-β. However, the inventive therapeutic approach is not limited to A-β targeting, and indeed Tregs which CARs which target other antigens, e.g., other AD antigens can readily be developed for use in treating AD or antigens expressed in other neuroinflammatory or neurodegenerative diseases. CAR cell therapy is a great approach for therapy because cells as drugs can traffic to sites of disease, persist in vivo (when engineered to do so), respond to environmental cues (e.g. antigen) to trigger or limit activities, and delivery multiple therapeutic mechanisms. The disclosure therefore provides methods, transduced Tregs and DNA constructs which provide for the enhanced persistence of CAR-expressing Tregs in the CNS and other tissues. The present disclosure specifically relates to CAR expressing Tregs which better retain the phenotype of Tregs and / or which persist for prolonged duration in the CNS and other tissues which include a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5B, a constitutively active STAT5A, and combinations thereof, wherein such cargo proteins may be expressed along with the CAR or induced as a result of CAR signaling; wherein such CAR expressing Tregs optionally may further be engineered to express neurodegenerative disease modifying molecules, e.g., which prevent oxidative / inflammatory activity, or which promote neuronal growth / survival such as nerve growth factors or non-classical neurotrophic factors. The present disclosure also generally relates to compositions containing such modified Tregs, methods of producing such Tregs, nucleic acids for producing such modified Tregs, and methods of use thereof as therapeutics, in particular for treating and preventing neurodegenerative diseases and symptoms associated therewith, and / or for slowing the onset of such 345733510.1 neurodegenerative diseases, particularly in persons at risk because of genetic factors or in persons exhibiting early signs of developing such neurodegenerative diseases. In some exemplary embodiments the CAR expressed by the Treg includes a binding region which recognizes at least one protein expressed at a site of inflammation or autoimmunity. In some exemplary embodiments the CAR expressed by the Treg includes a binding region which recognizes at least one protein expressed at a site of neurodegeneration or neuroinflammation. In some exemplary embodiments the CAR expressed by the Treg includes an scFv or ligand which recognizes at least one aberrant protein or aberrantly expressed protein expressed at a site of inflammation or autoimmunity. In some exemplary embodiments the CAR expressed by the Treg includes an scFv or ligand which recognizes at least one aberrant protein or aberrantly expressed protein expressed at a site of neurodegeneration or neuroinflammation. In some exemplary embodiments the CAR expressed by the Treg binds to a protein associated with a neurodegenerative disease or condition selected from human amyloid beta, amyloid-beta 1-42, alpha-synuclein, superoxide dismutase-1 (SOD-1), hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; and Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; P / Q-type calcium channel α1A subunit; TATA- box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C. In some exemplary embodiments the CAR expressed by the Treg binds to one or more of an amyloid protein, e.g., amyloid-beta protein, or a mutant superoxide dismutase 1, or human alpha- synuclein. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct encoding (1) a chimeric antigen receptor (CAR) and (2) a DNA encoding at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), and (3) optionally a DNA construct encoding a “neurodegenerative disease-modifying molecule” or “NDMM” or “disease-modifying molecule” or DMM; 445733510.1 wherein (i) the DNA encoding (1) and (2) and optionally (3) may be on the same or different constructs; (ii) expression of the DNA encoding (1) and (2) and optionally (3) may be controlled by the same or different inducible or constitutive promoters; (iii) the Treg including the DNA (1) and (2) and optionally (3) inducibly or constitutively expresses at least one of IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), the CAR and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the Treg persists longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen compared to a Treg which includes a DNA construct encoding the same (1) chimeric antigen receptor (CAR) but which does not include (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA). In some exemplary embodiments, modified Tregs according to the disclosure are human or murine. In some exemplary embodiments, modified Tregs according to the disclosure include a CAR which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of inflammation or autoimmunity. In some exemplary embodiments, modified Tregs according to the disclosure include a CAR specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition. In some exemplary embodiments, modified Tregs according to the disclosure may be used in treating a neurodegenerative or neuroinflammatory is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann- Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron 545733510.1 accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis. In some exemplary embodiments, modified Tregs according to the disclosure may be used to treat Alzheimer’s disease, or ALS. In some exemplary embodiments, modified Tregs according to the disclosure include a CAR which includes an scFv or ligand which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of inflammation or autoimmunity. In some exemplary embodiments, modified Tregs according to the disclosure include an scFv or ligand which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of neurodegeneration or neuroinflammation. In some exemplary embodiments, modified Tregs according to the disclosure include a CAR that specifically binds to an antigen selected from amyloid-beta 1-42, alpha-synuclein, superoxide dismutase-1 (SOD-1), hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43): chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA- binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), an antigen including Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C; or optionally to an amyloid protein, further optionally amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS. In some exemplary embodiments, modified Tregs according to the disclosure include (3) a DNA construct encoding at least one NDMM or DMM, optionally selected from IL-37, IL-33, IL-4, IL-10, IL-25, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro- neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, peroxiredoxins (Prxs); activity-dependent 645733510.1 neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, a nerve growth factor e.g., a classic neurotrophins such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G-CSF). In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct encoding a NDMM or DMM selected from BDNF or IGF-1. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct including (1) a CAR; (2) IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); and DMM coding sequences, optionally BDNF or IGF-1, which are oriented from 5’ to 3’ orientation in the CAR construct as follows: (1) CAR –(2) IL-2-(3) DMM or (1) CAR –(2) DMM-(3) IL-2. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct which includes at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4-CD3ζ, CD28, DAP10, 4-1BB, CD3ζ, and CD44, and optionally is selected from CD28-CD3ζ, DAP10- CD3ζ, CD44-CD3ζ, CD28 and CD3ζ. In some exemplary embodiments, modified Tregs according to the disclosure the CAR DNA is associated with a transmembrane (TM) region of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof. In some exemplary embodiments, modified Tregs according to the disclosure include a suicide gene or marker / targeting gene, optionally on the CAR construct, further optionally expressed under the control of an inducible promoter. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct which optionally includes a retroviral construct, further optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct, that optionally includes an IL-2 minimal promoter and NFAT binding sites. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct which includes (i) a CD44 costimulatory domain or CD44 intracellular domain, 745733510.1 wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain. In some exemplary embodiments, modified Tregs according to the disclosure include a DNA construct which includes: (1) a DNA encoding an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) a DNA encoding human IL-2 or a human IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); and (3) a DNA encoding BDNF or IGF-1. In some exemplary embodiments, modified Tregs according to the disclosure include a CAR DNA construct selected from JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A-hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A- BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A- mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5b-CA; and DG03.m28H,TM.m44cy.mZ-T2A- mSTAT5a-CA having the sequences in the informal Sequence Listing preceding the claims and / or includes a CAR DNA construct as schematically depicted in Figure 1 or Figure 2. In some exemplary embodiments, modified Tregs according to the disclosure the encoded CAR expressed by the DNA construct therein includes DG01, DG02, DG03, DG04, DG05, DG06, DG07, DG08, DG09, DG10, DG11, DG15, or DG16, and preferably includes DG03 or DG05, having the sequences contained in the informal Sequence Listing preceding the claims. In some exemplary embodiments, the disclosure provides a DNA construct encoding (1) a chimeric antigen receptor (CAR), which optionally binds to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, (2) a DNA encoding at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or includes a constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); optionally having the sequence contained in the Sequence Listing preceding the claims, and further optionally includes (3) a DNA encoding a “neurodegenerative disease-modifying molecule” or “NDMM” or “disease-modifying molecule” or DMM; wherein 45733510.1 (i) expression of the DNA encoding (1) and (2) and optionally (3) is controlled by the same or different inducible or constitutive promoters; (ii) the DNA construct including (1) and (2) and optionally (3) provides for the inducible or constitutive expression of IL-2 and the CAR and optionally a DMM or NDMM by a Treg containing same when introduced into a subject in need thereof; and (iii) the DNA construct when introduced into a Treg results in the Treg persisting longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen when introduced into a subject in need thereof compared to a Treg which includes a DNA construct encoding the same (1) chimeric antigen receptor (CAR) but which does not include (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA). In some exemplary embodiments, the encoded IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA) is human or murine. In some exemplary embodiments, the CAR encoded by the DNA construct binds to antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally Alzheimer’s disease or ALS. In some exemplary embodiments, the CAR in the DNA construct binds to an antigen, ligand or receptor expressed in a neurodegenerative or neuroinflammatory condition selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis, optionally Alzheimer’s disease, or ALS. In some exemplary embodiments, the DNA construct includes a DNA encoding at least one NDMM or DMM. 945733510.1 In some exemplary embodiments, the DNA construct includes a DNA encoding at least one NDMM or DMM selected from IL-37, IL-33, IL-4, IL-10, IL-25, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease- associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, a nerve growth factor e.g., a classic neurotrophins such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte- colony stimulating factor (G-CSF). In some exemplary embodiments, the DNA construct includes a DNA encoding at least one NDMM or DMM selected from BDNF or IGF-1. In some exemplary embodiments, the DNA construct includes (1) CAR, (2) IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); and (3) DMM coding sequences, optionally BDNF or IGF-1, which are oriented from 5’ to 3’ orientation in the CAR construct as follows: (1) CAR –(2) IL-2-(3) DMM or (1) CAR –(2) DMM-(3) IL-2. In some exemplary embodiments, the CAR encoded by the DNA construct includes an scFv or ligand which recognizes at least one aberrant protein or protein which is aberrantly expressed at a site of inflammation or autoimmunity. In some exemplary embodiments, the CAR encoded by the DNA construct includes an scFv or ligand which recognizes at least one aberrant protein or aberrantly expressed protein expressed at a site of neurodegeneration or neuroinflammation or at a site associated with the disease. In some exemplary embodiments, the CAR encoded by the DNA construct specifically binds to an antigen selected from amyloid-beta 1-42, alpha-synuclein, superoxide dismutase-1 1045733510.1 (SOD-1), hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43): chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), an antigen including Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C. In some exemplary embodiments, the CAR encoded by the DNA construct specifically binds to amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1). In some exemplary embodiments, the DNA construct further includes a DNA construct encoding a NDMM or DMM selected from BDNF or IGF-1. In some exemplary embodiments, the DNA construct includes at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4-CD3ζ, CD28, DAP10, 4-1BB and CD3ζ, and optionally includes CD28- CD3ζ or CD44-CD3ζ. In some exemplary embodiments, the DNA construct includes a suicide gene. In some exemplary embodiments, the CAR encoded by the DNA construct includes a retroviral construct, further optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct, that optionally includes an IL-2 minimal promoter and NFAT binding sites. In some exemplary embodiments, the DNA construct includes (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain. In some exemplary embodiments, the DNA construct includes (1) a DNA encoding an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) a DNA encoding human IL-2 or a human IL-2 mutein, and (3) a DNA encoding BDNF or IGF-1. In some exemplary embodiments, the DNA construct is selected from JC219 DG03.28.z- T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A-hIL2; JC221 DG05.28.Z-T2A- BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2- P2A-BDNF; JC228 DG03.m28.mZ-T2A-mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5b- CA; and DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5A-CA having the sequences in the informal 1145733510.1 Sequence Listing preceding the claims and / or includes a CAR DNA construct as schematically depicted in Figure 1 or Figure 2. In some exemplary embodiments, the CAR encoded by the DNA construct includes DG01, DG02, DG03, DG04, DG05, DG06, DG07, DG08, DG09, DG10 or DG11, and preferably includes DG03 or DG05, having the sequences contained in the informal Sequence Listing preceding the claims. In some exemplary embodiments, the DNA construct includes a sequence encoding one or more NFAT binding sites, optionally a sequence encoding at least 4, 6 or 9 NFAT binding sites. In some exemplary embodiments, the CAR encoded by the DNA construct is expressed under the control of one or more of a viral promoter, a mammalian promoter, an LTR, an IL-2 promoter, optionally an IL-2 minimal promoter, further optionally an IL-2 minimal promoter, a T2A / P2A signal, or an IRES, optionally IRES-FGF2. In some exemplary embodiments, the disclosure provides a method of treating a neuroinflammatory or neurodegenerative disease in a subject in need thereof which includes introducing an effective amount of Tregs according to any one of the foregoing; optionally wherein the neuroinflammatory or neurodegenerative disease is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral- pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis; further optionally wherein the neuroinflammatory or neurodegenerative disease is Alzheimer’s disease or ALS; further optionally wherein the Tregs are produced in vitro and optionally expanded prior to administration; or further optionally wherein the Tregs are administered via one or more of intravenous (IV), intra-cisterna magna (ICM), intracerebroventricular (ICV) or intrathecal routes; or optionally wherein the Tregs are administered intravenously; or optionally wherein the Tregs are administered fresh; or optionally wherein the 1245733510.1 Tregs are administered as frozen / thawed cells; or optionally wherein the subject is additionally treated with low dose IL-2, optionally weekly or monthly; or optionally wherein the dose of Tregs ranges from about 0.5 x 106Tregs / kg up to about 30 x 106Tregs / kg; or the dose of Tregs ranges from 30 x 106 cells to about 3x 109cells, optionally for 60kg to 100kg patients; or the subject has or is taking one or more AD medications, optionally selected from Galantamine, rivastigmine, donepezil and other cholinesterase inhibitors, memantine, Crenezumab, Bapineuzumab, Donanemab, Huperzine A, Lecanemab, protolitin, ponezumab, Sodium oligomannate, or Solanezumab; or the previous claims, wherein the treated subject has a gene defect correlated with AD, optionally a mutation of amyloid precursor protein (APP) gene included on chromosome 21, a mutation of Presenilin 1 (PSEN1) on chromosome 14, a mutation of Presenilin 2 (PSEN2) on chromosome 1, or includes at least one copy of APOE-e4; or the treated subject has early onset AD or late-onset AD; or the levels and / or ratios of inflammatory cytokines or mediators, optionally one or more of TNFα, CCL2, CCL3, CCL4, NOX2, Il-1β, and IL-6 are detected; or wherein the detected levels and / or ratios of inflammatory cytokines or mediators, optionally one or more of TNFα, CCL2, CCL3, CCL4, NOX2, Il-1β, and IL-6 are used as part of an assessment as to whether to administer Tregs which express a CD44 costimulatory domain containing CAR or Tregs which express a CD28 or Dap10 costimulatory domain containing CAR. In some forms, the described modified Tregs are transduced and / or stimulated according to a methodology designed for optimal Treg cell expansion, viability, CAR expression, and to maintain the Treg phenotype. In exemplary forms, cells are stimulated with anti-CD3 / 28 / 2 tetramer combinations. In some forms, the Tregs are stimulated on days 0 and day 9 with transduction on days 10 & 11, or stimulation on days 0, 7, and 14 with transductions on days 15 & 16. In some exemplary embodiments, the Treg cell does not express a functional TCR. In some exemplary embodiments, the Treg cell is further engineered to express at least one anti-oxidant, nerve growth factor or non-classical neurotrophic factor the expression of which is optionally under the control of an inducible promoter. In some exemplary embodiments, the Treg cell when administered crosses the BBB. In some exemplary embodiments, the Treg cell possesses Treg effector functions. In some exemplary embodiments, the Treg cell expresses Treg surface markers and / or expresses IL-10 or a viral variant of IL-10. In some exemplary embodiments, the Treg cells does not include a nucleic acid construct encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA). In such embodiments, the methods include co-administration of the modified Treg and (i.e., exogenous) IL-2, an IL-2 mutein or constitutively active STAT5B 1345733510.1 (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA), either as a polypeptide, or nucleic acid encoding the same to the subject. Thus, all of the disclosed constructs are also expressly provided without a nucleic acid sequence encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA) as are methods of use thereof for treating all of the disclose indications, where the IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA) is co-administered to the subject and the same or separate admixture as the Tregs. In some exemplary embodiments, the present disclosure provides a method of producing a modified Treg according to the present disclosure. In some exemplary embodiments, the method may include introducing any of the nucleic acid constructs or a combination thereof into a cell, such as an immune cell or a cell of T cell lineage, e.g., Treg. BRIEF DESCRIPTION OF THE DRAWING FIGURE 1 contains a schematic of exemplary CAR constructs containing inducible or constitutive cargos. FIGURE 2 also contains a schematic of exemplary CAR constructs containing two inducible or constitutive cargo genes and DMMs. FIGURE 3 shows flow cytometry analysis of CAR expression on human Tregs transduced with a CAR only or a CAR with IL-2 cargo gene. Mock Tregs are included as a control. FIGURES 4A-4C contain experimental results showing that mSOD1-NSG mice injected with human Tregs, which express a CAR construct with an IL-2 gene included, are present in mSOD1-NSG mice and have higher numbers in the spinal cord tissue and spleen (ALS model) than those injected with human Tregs which express the same CAR construct but which lacks an IL-2 gene. FIG.4A shows CD52 (fold change) for each group in the spinal cord; FIG.4B shows CD52 (fold change) for each group in the spleen; and FIG.4C shows CAR (mRNA signal) for each group in the spleen. In the experiments a first group of mSOD1-NSG mice were injected with Tregs including SOD1 specific CARs, i.e., “JC172” which includes an SOD-1 CAR and BDNF; a second group of mSOD1-NSG mice were injected with Tregs including a CAR referred to as “JC221” which includes an SOD-1 CAR, BDNF and IL-2; and a third group of mSOD1-NSG mice were injected with vehicle alone (“veh”). CD52 is highly expressed on human Tregs. Mice that had no CD52 signal were set to a value of 1. FIGURE 5 contains experimental results showing that human Tregs transduced with vectors express a CAR and Treg markers regardless of whether the vector also expresses an IL-2 1445733510.1 cargo gene. Tregs were transduced with amyloid-beta specific CAR vectors, i.e., CAR Treg (BA38 (DG03-443z)) or CAR Treg w / IL-2 (JC220 (DG03-443z w IL-2)). FIGURES 6A-6D contain experimental results showing tissues from 5xFAD-NSG mice that had been injected with human Tregs 3 weeks earlier and were assessed for the presence of CAR Tregs by expression of human CD52 or the CAR itself by qPCR. FIGs.6A-6B show histogram plots of in vitro analyses for each of IL-2 (pg / ml) production (FIG.6A); and IL-10 (pg / ml) production (FIG.6B), respectively, for each group; FIGs.6C-6D show histogram plots of in vivo analyses for each of CD52 in the cortex (fold change) (FIG.6C); and CD52 in the spleen (fold change) (FIG.6D), respectively. The results in the figure show a higher amount of Tregs in CNS and spleen when CAR w IL-2 Tregs were injected into 5xFAD-NSG mice rather than CAR Tregs alone. In vitro analysis of cytokine production of the injected Tregs show that the CAR w IL-2 Tregs produce IL-2 constitutively, and both types of Tregs are triggered to produce IL-10 when the CAR antigen is coated on the wells resulting in CAR triggered activation of the Tregs. FIGURES 7A-7C contain experimental results showing that human Tregs which were transduced with an amyloid-beta specific CAR that did or did not also contain an IL-2 gene (constitutive IL-2 or cIL-2), i.e., BA38 (DG03-443z and no IL-2 construct) or JC220 (DG03-443z with IL-2 construct), express the CAR on the cell surface and expected human Treg markers: CD25, FoxP3, Helios, but not CD127. Furthermore, the Tregs transduced with a CAR and IL-2 construct constitutively expressed IL-2, which was increased upon CAR activation by antigen. FIGs.7A-7B shows a panel of FLOW cytometry plots for each of CAR Treg and CAR-cIL2 Tregs, respectively, stained for each of CAR, CD25 and CD127 (FIG.7A); and FoxP3 and Helios (FIG.7B), respectively. FIG.7C is a histogram showing IL-2 production (pg / ml) for each group. FIGURES 8A-8B contain experimental results showing analysis of human Tregs from tissues isolated from 5xFAD-NSG mice injected with amyloid-beta specific CAR Tregs IV 4 weeks earlier. FIG.8A shows CD52 in cortex (mRNA signal); and FIG.8B shows CD52 in spleen (mRNA signal), for each group, respectively. In these experiments 5xFAD-NSG mice were injected with Tregs including a DG03 CAR (amyloid-beta specific CAR, i.e., BA38 (DG03-443z and no IL- 2 construct) or JC220 (DG03-443z with IL-2 construct) and not treated with additional exogenous IL-2. The results show higher amounts of human Tregs in CNS and spleen when 5xFAD-NSG mice were injected with CAR Tregs that also express IL-2 compared to CAR Tregs alone. Vehicle treated 5xFAD-NSG mice had no CD52 signal and were set to a value of 1. FIGURES 9A-9C contain experimental results showing that human Tregs which include a CAR construct including IL-2, BDNF, and a SOD-1 specific CAR. FIG.9A shows cell growth (fold change over days); FIG.9B shows IL-10 (pg / ml); and FIG.9C shows IL-2 and BDNF 1545733510.1 (pg / ml), respectively for each group. In these experiments Tregs expressing a SOD1 specific CAR, JC225 (DG05-IL-2-BDNF) were used. As can be seen from the results in the figure, whether the CAR Tregs were grown with rapamycin or without, they produced IL-10 in response to CAR antigen and constitutively made both IL-2 and BDNF, which expression increased upon CAR activation via plate-bound antigen. FIGURE 10 contains experimental results showing that human Tregs which include a CAR construct and IL-2, IL-2 mutein (IL-2m), or mock transduced, and analyzed by flow cytometry for CAR expression, FoxP3 expression, and Helios expression. Specific staining is shown in red and background in blue. FIGURE 11 contains experimental results showing that human Tregs which include a CAR construct and IL-2, IL-2 mutein (IL-2m), or mock transduced, cultured in streptavidin-coated wells)+SA) or streptavidin-coated wells and biotin-amyloid-beta peptides wells (+SA+AB). Cell- free media was collected after 1 day, and analyzed for IL-2 using a IL-2 ELISA. FIGURE 12 contains experimental results showing that CAR Tregs co-expressing IL-2 survive longer in vivo. DG05 CAR Tregs that recognize aggregated human SOD1 and co-express IL-2 were evaluated in different tissues from 3d to 28d after IV injection in mSOD1-NSG mice. CD52 mRNA (a gene highly expressed in human Tregs) was determined by qPCR. Data are shown for each tissue as compared to the amount of CD52 on d3. FIGURE 13 contains experimental results showing that CAR Tregs co-expressing IL-2 survive longer than CAR Tregs alone in vivo. Two experiments using DG05 scFv CAR Tregs co- expressing a persistence factor (PF) show the presence and persistence of Tregs over the time course. In this example, the PF is IL-2. The DG05 CAR Tregs alone decreased after 7d and were found at much lower amounts on day 25. The presence of CAR Tregs in the spinal cord was measured by qPCR for human CD52. Data are from independent experiments, and each data point is an average of 3 or 4 mice per time point. DETAILED DESCRIPTION The present disclosure generally relates to methods, cells and DNA constructs for use in such methods which provide for the enhanced persistence of CAR-expressing Tregs in the CNS and other tissues. The present disclosure also specifically relates to CAR expressing Tregs which retain the phenotype of Tregs and / or which persist for prolonged duration in the CNS and other tissues after being introduced into a subject in need thereof which include a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5B, or constitutively active STAT5A (STAT5A-CA); and 1645733510.1 combinations thereof, wherein such cargo proteins may be expressed along with the CAR or induced as a result of CAR signaling. The present disclosure also relates to methods for producing CAR expressing Tregs which retain the phenotype of Tregs and which better persist in the CNS by introducing a cargo protein that results in the expression of IL-2 and / or which triggers the IL-2 receptor pathway such as human IL-2, an IL-2 mutein, a constitutively active STAT5B, or constitutively active STAT5A; or combinations of any of the foregoing. The present disclosure further relates to compositions containing such modified Tregs, and methods of use thereof as therapeutics, e.g., for treating and preventing neurodegenerative diseases and symptoms associated therewith, and / or for slowing the onset of such neurodegenerative diseases such as Alzheimer’s disease and ALS. In exemplary embodiments, these recombinant or modified Tregs may be engineered to express one or more CARs, wherein the one or more CARs may target different proteins and / or molecular markers associated with the pathology of particular neurodegenerative diseases and conditions. These CARs optionally may further include a costimulation signaling or T cell signaling moiety such as CD28-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CD28 or CD3ζ or another costimulatory signaling or T cell signaling moiety. Modified Tregs according to the disclosure will preferably be engineered to express one or more neurodegenerative disease modifying molecules (NDMMs) which may be on the same or different nucleic acid construct as the CAR or may be expressed on modified Tregs which do not include a CAR. In preferred embodiments modified Tregs according to the disclosure express a CAR DNA construct wherein the CAR, 2 or IL-2 mutein or STAT5B- CA or STAT5A-CA, and NDMM or DMM are in the following orientation in the DNA construct: (1) [CAR]--(2) [IL-2 or IL-2 mutein or STAT5B-CA or STAT5A-CA]-- (3) [NDMM or DMM] or (1) [CAR]--(2) [NDMM or DMM] (3) -- [IL-2 or IL-2 mutein or STAT5B-CA or STAT5A-CA]. The present disclosure specifically contemplates modified Tregs expressing one or more specific CARs targeting a neurodegenerative disease, IL-2 or a IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); and a neurodegenerative disease modifying molecule (NDMM), pharmaceutical compositions including the modified Tregs, and methods of making and using these modified Tregs in therapy wherein such modified Tregs persist longer in the CNS and / or the spleen because of the IL-2 or a IL-2 mutein or constitutively 1745733510.1 active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); which is expressed by the CAR construct therein. The present disclosure also provides methods for treating a neurodegenerative disease, disorder, or condition, a subject, such as but not limited to Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis (ALS), and neuroinflammation using these modified Tregs. I. DEFINITIONS As used herein, the terms “neurodegenerative disease”, “neurodegenerative disorder”, and “neurodegenerative condition” generally refer to any disease, disorder, and / or condition that affects the neurons (sometimes referred to as “nerve cells”), such as neurons of a brain and / or neurons of a nervous system which is associated with the degeneration or loss of neural cells. Often, neurodegenerative diseases may result in progressive degeneration and / or death of nerve cells. In general neurodegeneration is the progressive loss of structure or function of neurons, including the death of neurons. Neurodegenerative diseases may cause problems with movement (called ataxias), or mental or cognitive functioning (called dementias). Frequently neurodegeneration is associated with neuroinflammation and indeed the onset, progression or cause of many debilitating neurodegenerative diseases is thought to involve neuroinflammation. Therefore, it is to be understood that the terms neurodegenerative disease and neurodegenerative disorder and the like encompass neural diseases which are characterized by neuroinflammation. Sometimes in such diseases activated microglia may produce inflammatory cytokines that contribute to widespread inflammation and may lead to and / or result in a neurodegenerative condition and / or disease. Furthermore, some neurodegenerative diseases and / or conditions are associated with microglia cell over-activation, increased numbers of microglia cells, production of inflammatory proteins and / or inflammatory activities, and / or neuronal death. Examples of such neurodegenerative diseases include by way of example Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; 1845733510.1 frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. In exemplary embodiments, a neurodegenerative disease may include Alzheimer’s disease, Parkinson’s disease, and / or ALS. In exemplary embodiments, modified Tregs cells as described herein may be used in a method of treating these and other neurodegenerative diseases. As used herein, the term “neuroinflammation” generally refers to inflammation of the nervous tissue. Sometimes, activated microglia may produce inflammatory cytokines that contribute to widespread inflammation and may lead to and / or result in a neurodegenerative condition and / or disease. In some instances, neuroinflammation may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, and / or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues, and generally generate reactive oxygen species and release signals to recruit peripheral immune cells for an inflammatory response. Cytokines may also be present at the sites of and / or may cause neuroinflammation, and in some instances they may be produced by microglia or macrophages. In exemplary embodiments, neuroinflammation may be associated with and / or may arise during a neurodegenerative disease, e.g., Alzheimer’s disease, ALS, and Parkinson’s disease. The term “inflammation” refers to a broad physiological response mediated by various cell types, proteins, humoral factors, and tissues. While inflammation can send signals within a body to help the immune system eliminate pathogens or undesired conditions, inappropriate levels or altered types of inflammation can cause numerous physiological or immunological problems within the body. Such inflammation can be directly responsible for the pathology of various diseases including autoimmune diseases, fibrotic diseases, chronic infections, and allergies (Laria, A. et al., “The macrophages in rheumatic diseases”, J Inflamm Res.2016 Feb 9;9: p.1-11; Wynn, T.A., and Ramalingam, T.R., “Mechanisms of fibrosis: fibrotic translation for fibrotic diseases”, Nat Med, 2012 Jul 6;18(7): p.1028-40; Yang, Z.P., Kuo, C.C., and Grayston, J.T, “Systemic dissemination of Chlamydia pneumoniae following intranasal inoculation in mice”, J Infect Dis.1995 Mar;171(3): p. 736-8 ; Jian, Z., and Zhu, L., “Update on the role of alternatively activated macrophages in asthma”, J Asthma Allergy, 2016 Jun 3;9: p.101-7). Inflammation can also indirectly exacerbate the symptoms of many diseases, or play an assisting role in the pathogenesis, for example in cancers, obesity, metabolic diseases, and cardiovascular diseases, such as atherosclerosis (Coussens, L.M., and Werb, Z., “Inflammation and Cancer”. Nature.2002 Dec 19-26;420(6917): p.860-7; Monteiro, R., and Azevedo, I., “Chronic inflammation in obesity and the metabolic syndrome”, Mediators 1945733510.1 Inflamm.2010;2010; Libby, P., “Inflammation and cardiovascular disease mechanisms”, Am J Clin Nutr.2006 Feb;83(2): p.456S-460S). The term “neurodegenerative disease-modifying molecule” or “NDMM” as used herein generally refers to a molecule capable of altering (reducing, ameliorating or preventing) the symptoms, progression or onset of a neurodegenerative disease, disorder, or condition. Representative neurodegenerative conditions include by way of example Alzheimer’s disease, ALS, Parkinson’s disease, and other neuroinflammatory conditions. Examples of such NDMM molecules include, but are not limited to including, IL-37, IL-4, IL-10, IL-25, IL-33, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease- associated protein. In exemplary embodiments, an NDMM may include one or more cytokines. In other exemplary embodiments, an NDMM may include molecules that prevent oxidative / inflammatory activity. In other exemplary embodiments, an NDMM may include molecules that promote neuronal growth and / or survival. In exemplary embodiments, an NDMM may be expressed by modified Tregs according to the disclosure, e.g., modified Tregs including one or more CARs, as discussed in further detail herein. Furthermore, an NDMM may include one or more pro-neuronal factors, one or more anti-oxidants, one or more nerve growth factors, and / or one or more non-classical neurotrophic factors. Examples of pro-neuronal factors include, but are not limited to including, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs). Examples of antioxidants include, but are not limited to including, HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin. Examples of nerve growth factors include, but are not limited to, classic neurotrophins such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and glial cell-line derived neurotrophic factor (GDNF). Non-limiting examples of non-classical neurotrophic factors include insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G-CSF). In some embodiments, NDMM expression may be controlled by an inducible promoter system, e.g., using one known in the art, and / or expression of the NDMM may be regulated by CAR-triggered transcriptional control. As used herein, a “5' cap” (also termed an RNA cap, an RNA 7-methylguanosine cap or an RNA m7G cap) is a modified guanine nucleotide that has been added to the "front" or 5' end of a 2045733510.1 eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal group which is linked to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases. Cap addition is coupled to transcription, and occurs co- transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction. The capping moiety can be modified to modulate functionality of mRNA such as its stability or efficiency of translation. The term "allogeneic" or “donor-derived” generally refers to any material derived from a different animal of the same species as the individual to whom the material is to be introduced or transplanted. Two or more individuals are the to be allogeneic to one another when the genes at one or more loci are not identical. In some aspects, allogeneic or “donor-derived” material from individuals of the same species may be sufficiently dissimilar genetically to interact antigenically. The term “antibody” or “Ab,” as used herein, refers to an immunoglobulin molecule which specifically binds with an antigen. In some embodiments, the antigen may be a molecule expressed or aberrantly expressed by neurons in subjects including a neurodegenerative disease and / or condition. Examples of such diseases and conditions include, but are not limited to including, Alzheimer’s disease, FTD, Parkinson’s disease, and ALS. Further non-limiting examples include prion disease, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann- Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. An "antibody" is intended to denote an immunoglobulin molecule, that possesses a "variable region" antigen recognition site. The term antibody includes monoclonal antibodies, multi-specific antibodies, human antibodies, humanized 2145733510.1 antibodies, synthetic antibodies, chimeric antibodies, camelized antibodies (See e.g., Muyldermans et al., 2001, Trends Biochem. Sci.26:230; Nuttall et al., 2000, Cur. Pharm. Biotech.1:253; Reichmann and Muyldermans, 1999, J. Immunol Meth..231:25; International Publication Nos. WO 94 / 04678 and WO 94 / 25591; U.S. Patent No.6,005,079), single-chain Fvs (scFv) (see, e.g., Pluckthun in The Pharmacology of Monoclonal Antibodies, vol.113, Rosenborg and Moore eds. Springer-Verlag, New York, pp.269-315 (1994)), single chain antibodies, disulfide-linked Fvs- (sdFv), intrabodies, and anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id and anti-anti-Id antibodies to antibodies). The term is used in the broadest sense and includes polyclonal and monoclonal antibodies, including intact antibodies and functional (antigen-binding) antibody fragments. The term encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, e.g., bispecific, antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv. Unless otherwise stated, the term "antibody" should be understood to encompass functional antibody fragments thereof. The term also encompasses intact or full-length antibodies, including antibodies of any class or sub- class. In particular, such antibodies include immunoglobulin molecules of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclasses thereof. As used herein, the term "fragment" refers to a peptide or polypeptide including an amino acid sequence of at least 5 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 15 contiguous amino acid residues, at least 20 contiguous amino acid residues, at least 25 contiguous amino acid residues, at least 40 contiguous amino acid residues, at least 50 contiguous amino acid residues, at least 60 contiguous amino residues, at least 70 contiguous amino acid residues, at least 80 contiguous amino acid, residues, at least 90 contiguous amino acid residues, at least 100 contiguous amino acid residues, at least 125 contiguous amino acid residues, at least 150 contiguous amino acid residues, at least 175 contiguous amino acid residues, at least 200 contiguous amino acid residues, or at least 250 contiguous amino acid residues An "antibody heavy chain," or “HC” as used herein, refers to the larger of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations. An "antibody light chain," or “LC” as used herein, refers to the smaller of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations. Kappa and lambda light chains refer to the two major antibody light chain isotypes. The term "variable region", or “VR” in the context of an immunoglobulin is intended to distinguish such domains of the immunoglobulin from domains that are broadly shared by 2245733510.1 antibodies (such as an antibody Fc domain). The variable region includes a "hypervariable region" or “HVR” whose residues are responsible for antigen binding. The terms "complementarity determining region," and "CDR," synonymous with "hypervariable region" or "HVR," are known in the art to refer to non-contiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and / or binding affinity. In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3). "Framework regions" and "FR" are known in the art to refer to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length light chain variable region (FR-L1, FR-L2, FR-L3, and FR-L4). The hypervariable region includes amino acid residues from a "Complementarity Determining Region" or "CDR" (i.e., typically at approximately residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the light chain variable domain and at approximately residues 27-35 (H1), 50-65 (H2) and 95-102 (H3) in the heavy chain variable domain; Kabat and Wu, et al., Sequences of Proteins of immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and / or those residues from a "hypervariable loop" (i.e., residues 26-32 (L1), 50-52 (L2) and 91-96 (L3) in the light chain variable domain and 26-32 (H1), 53-55 (H2) and 96-101 (H3) in the heavy chain variable domain; Chothia and Lesk, 1987, J. Moi Biol 196:901-917). "Framework Region" or "FR" residues are those variable domain residues, other than the hypervariable region residues as herein defined. The term " antigen binding fragment" or “Ab fragment” of an antibody refers to one or more portions of an antibody that contain the antibody's Complementarity Determining Regions ("CDRs") and optionally the framework residues that include the antibody's "variable region" antigen recognition site, and exhibit an ability to immuno-specifically bind antigen. For example, an antigen binding fragment of an intact antibody refers to the antigenic determining variable regions of an intact antibody. Examples of binding fragments include, but are not limited to, fragment antigen binding (Fab) fragments, F(ab')2fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single chain antibody fragments, including single chain variable fragments (scFv), single domain antibodies (e.g., sdAb, sdFv, nanobody) fragments, diabodies, and multispecific antibodies formed from antibody fragments. In exemplary embodiments, the antigen binding fragment may be an scFv. By the term "synthetic antibody" as used herein, is meant an antibody which is generated using recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage as described herein. The term should also be construed to mean an antibody which 2345733510.1 has been generated by the synthesis of a DNA molecule encoding the antibody and which DNA molecule expresses an antibody protein, or an amino acid sequence specifying the antibody, wherein the DNA or amino acid sequence has been obtained using synthetic DNA or amino acid sequence technology which is available and well known in the art. As used herein, a "chimeric antibody" is a molecule in which different portions of the antibody are derived from different immunoglobulin molecules such as antibodies having a variable region derived from a non-human antibody and a human immunoglobulin constant region. The term "antigen" or "Ag" refers to a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which includes a nucleotide sequence or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an "antigen" as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. It is readily apparent that the present disclosure includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to encode polypeptides that elicit the desired response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a "gene" at all. It is readily apparent that an antigen can be generated, synthesized, or can be derived from a biological sample, or might be a macromolecule besides a polypeptide. Such a biological sample can include, but is not limited to a tissue sample, a neurological tissue sample, an inflamed tissue sample, a cell, or a fluid with other biological components. In some embodiments, the antigen is a molecule expressed in a neurodegenerative disease or condition, e.g., Alzheimer’s disease, Parkinson’s disease, and ALS. In exemplary embodiments, an antigen may be a form of any one or more of the following that may be associated with a neurodegenerative disease or condition: amyloid-beta 1-42, alpha-synuclein, superoxide dismutase-1 (SOD-1), hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43): chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2). In some embodiments, an antigen may be a form of any one or more of the following that may be associated with a neurodegenerative disease or condition: Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; ataxins; P / Q-type calcium channel 2445733510.1 α1A subunit; TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; cystatin C. The term “antigen binding domain” or “AB domain” refers to one or more extracellular domains of a chimeric antigen receptor (CAR) which have specificity for a particular antigen. The term "apheresis" as used herein refers to the art-recognized extracorporeal process by which the blood of a donor or patient is removed from the donor or patient and passed through an apparatus that separates out selected particular constituent(s) and returns the remainder to the circulation of the donor or patient, e.g., by retransfusion. Thus, in the context of "an apheresis sample" refers to a sample obtained using apheresis. The term "autologous" or refers to any material derived from the same individual to whom it is later to be re-introduced. The term “bind” refers to an attractive interaction between two molecules that results in a stable association in which the molecules are in close proximity to each other. The result of molecular binding is sometimes the formation of a molecular complex in which the attractive forces holding the components together are generally non-covalent, and thus are normally energetically weaker than covalent bonds. The term "CD28" refers to the protein Cluster of Differentiation 28, one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. Mouse CD28 protein may have at least 85, 90, 95, 96, 97, 98, 99 or 100% identity to NCBI Reference No: NP_031668.3 or a fragment thereof that has stimulatory activity. Human CD28 protein may have at least 85, 90, 95, 96, 97, 98, 99 or 100% identity to NCBI Reference No: NP_006130 or a fragment thereof that has stimulatory activity. The term “CD3 zeta,” or alternatively, "zeta,” "ζ," “zeta chain,” "CD3-zeta," “CD3z,” "TCR-zeta," “CD247,” or “CD3ζ” is a protein by the CD247 gene on chromosome 1, with gene location 1 H2.3; 173.14 cM, in mice, and by the CD247 gene on chromosome 1, with gene location 1q24.2, in humans. CD3 ζ, together with T cell receptor (TCR) and CD3 (a protein complex composed of a CD3 γ, a CD3 δ and two CD3 ε), forms the TCR complex. Mouse CD3 ζ may have an amino acid sequence provided as NP_001106864.1, NP_001106863.1, NP_001106862.1, or NP_112439.1, or the equivalent residues from a non-mouse species, e.g., human, rodent, monkey, ape and the like. Human CD3 ζ may have an amino acid sequence provided as NP_000725 or NP_932170, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like. The term "CD3 zeta intracellular signaling domain," or alternatively "CD3 zeta ICS domain" or a "CD3zICS," is defined as the amino acid residues from the cytoplasmic domain of the 2545733510.1 CD3 zeta chain, or functional derivatives thereof, that are sufficient to functionally transmit an initial signal necessary for T cell activation. The term "4-1BB" or “BB” refers to a member of the TNFR superfamily with an amino acid sequence provided as GenBank Acc. No. AAA53133.1, or the equivalent residues from a non- human species, e.g., mouse, rodent, monkey, ape and the like. In some embodiments the "4-1BB costimulatory domain" has the sequence contained in the Sequence Listing preceding the claims. The term "Chimeric Antigen Receptor" or alternatively a "CAR" refers to a set of polypeptides, typically two in the simplest embodiments, which when expressed in an immune effector and / or regulatory cell, provides the cell with specificity for a target cell, and optionally promotes intracellular signal generation. CARs according to the disclosure will in general include a receptor or ligand binding moiety, e.g., one which targets a protein aberrantly expressed in subjects including a neurodegenerative disorder and optionally may include one or more costimulatory signaling or T cell signaling domains such as CD28, 4-1BB, CD3ζ, DAP10-CD3ζ CD44-CD3ζ, CD28-CD3ζ, or 4-1BB-CD3ζ. In some embodiments, a CAR includes at least an extracellular antigen binding domain (AB domain), a transmembrane domain (TM domain) and a cytoplasmic signaling domain (also referred to herein as "an intracellular signaling domain (ICS domain) including a functional signaling domain derived from a stimulatory molecule and / or costimulatory molecule as defined below. In some aspects, the set of polypeptides are contiguous with each other. In some embodiments, the set of polypeptides include a dimerization switch that, upon the presence of a dimerization molecule, can couple the polypeptides to one another, e.g., can couple an AB domain to an ICS domain. In some aspects, the stimulatory molecule is the zeta chain associated with the T cell receptor complex. In some aspects, the cytoplasmic portion of a CAR further includes a costimulatory domain (CS domain) including one or more functional signaling domains derived from at least one costimulatory molecule as defined below. In some aspects, the costimulatory molecule is chosen from the costimulatory molecules described herein, e.g., 4-1BB (i.e., CD137), CD44, DAP10 and / or CD28. In some aspects, the CAR includes a chimeric fusion protein including an extracellular AB domain, a TM domain and an ICS domain including a functional signaling domain derived from a stimulatory molecule. In some aspects, the CAR includes a chimeric fusion protein including an extracellular AB domain, a TM domain, an ICS domain including a functional signaling domain derived from a stimulatory molecule, and a CS domain including a functional signaling domain derived from a costimulatory molecule. In some aspects, the CAR includes a chimeric fusion protein including an extracellular AB domain, a TM domain, an ICS domain including a functional signaling domain derived from a stimulatory molecule, and two CS domains each of the two including a functional signaling domain derived 2645733510.1 from a costimulatory molecule(s) that is / are same with or different from each other. In some aspects, the CAR includes a chimeric fusion protein including an extracellular AB domain, a TM domain, an ICS domain including a functional signaling domain derived from a stimulatory molecule, and at least two CS domains each including a functional signaling domain derived from a costimulatory molecule(s) that is / are same with or different from each other. In some aspects, the CAR includes an optional leader sequence at the amino-terminus (N-ter) of the CAR fusion protein. In some aspects, the CAR further includes a leader sequence at the N-terminus of the extracellular antigen binding domain, wherein the leader sequence is optionally cleaved from the antigen binding domain (e.g., an scFv) during cellular processing and localization of the CAR to the cellular membrane. As used herein, the terms "antigenic determinant'' and "epitope" are used interchangeably and refer to the structure recognized by an antibody. As used herein, a "conformational epitope" is an epitope that includes discontinuous sections of the antigen's amino acid sequence. Antibodies bind a conformational, epitope based on 3-D surface features, shape, or tertiary structure of the antigen. As used herein, a "linear epitope" is an epitope that is formed by a continuous sequence of amino acids from the antigen. Linear epitopes typically include about 5 to about 10 continuous amino acid residues. Antibodies bind a linear epitope based on the primary sequence of the antigen. As used herein, a "paratope," also called, an "antigen-binding site," is a part of an antibody which recognizes and binds to an antigen. The term "compete", as used herein with regard to an antibody, means that a first antibody, or an antigen binding fragment (or portion) thereof, binds to an epitope in a manner sufficiently similar to the binding of a second antibody, or an antigen binding portion thereof, such that the result of binding of the first antibody with its cognate epitope is detectably decreased in the presence of the second antibody compared to the binding of the first antibody in the absence of the second antibody. The alternative, where the binding of the second antibody to its epitope is also detectably decreased in the presence of the first antibody, can, but need not be the case. That is, a first antibody can inhibit the binding of a second antibody to its epitope without that second antibody inhibiting the binding of the first antibody to its respective epitope. However, where each antibody detectably inhibits the binding of the other antibody with its cognate epitope or ligand, whether to the same, greater, or lesser extent, the antibodies are the to "cross-compete" with each other for binding of their respective epitope(s). Both competing and cross-competing antibodies are encompassed by the disclosure. Regardless of the mechanism by which such competition or cross- competition occurs (e.g., steric hindrance, conformational change, or binding to a common epitope, or portion thereof), the skilled artisan would appreciate, based upon the teachings provided herein, 2745733510.1 that such competing and / or cross-competing antibodies are encompassed and can be useful for the methods disclosed herein. The term "costimulatory molecule" or “T cell signaling moiety” herein refers to a cognate binding partner on a T cell that specifically binds with a costimulatory ligand, thereby mediating a costimulatory response by the T cell, such as, but not limited to, proliferation or the expression of specific cytokines. Costimulatory molecules are cell surface molecules other than antigen receptors or their ligands that contribute to an efficient immune response. Costimulatory molecules include, but are not limited to a protein selected from the group consisting of an MHC class I molecule, TNF receptor proteins, Immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocytic activation molecules (SLAM proteins), activating NK cell receptors, a Toll ligand receptor, B7-H3, BAFFR, BTLA, BLAME (SLAMF8), CD2, CD4, CD5, CD7, CD8α, CD8β, CD11a, LFA-1 (CD11a / CD18), CD11b, CD11c, CD11d, CD18, CD19, CD19a, CD27, CD28, CD29, CD30, CD40, CD44, CD49a, CD49D, CD49f, CD69, CD84, CD96 (Tactile), CD100 (SEMA4D), CD103, OX40 (CD134), 4-1BB (CD137), SLAM (SLAMF1, CD150, IPO-3), CD160 (BY55), SELPLG (CD162), DNAM1 (CD226), Ly9 (CD229), SLAMF4 (CD244, 2B4), ICOS (CD278), CEACAM1, CDS, CRTAM, DAP10, GADS, GITR, HVEM (LIGHTR), IA4, ICAM-1, IL2R β, IL2R γ, IL7R α, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, ITGB7, KIRDS2, LAT, LFA-1, LIGHT, LTBR, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80 (KLRF1), PAG / Cbp, PD-1, PSGL1, SLAMF6 (NTB-A, Ly108), SLAMF7, SLP- 76, TNFR2, TRANCE / RANKL, VLA1, VLA-6, and a ligand that specifically binds with CD83. In embodiments wherein a CAR includes one or more CS domains, wherein each CS domain includes a functional signaling domain derived from a costimulatory molecule. In some embodiments, the encoded CS domain is that of 4-1BB, CD28, or DAP10. The term “cytokines” refers to a broad category of small proteins that are involved in cell signaling. Generally, their release has some effect on the behavior of cells around them. Cytokines may be involved in autocrine signaling, paracrine signaling and / or endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, epithelial cells, and various stromal cells. “Chemokines” are a family of cytokines generally involved in mediating chemotaxis. An “effective amount” or “an amount effective to treat” refers to a dose that is adequate to prevent or treat a disease, condition, or disorder in an individual. Amounts effective for a therapeutic or prophylactic use will depend on, for example, the stage and severity of the disease or 2845733510.1 disorder being treated, the age, weight, and general state of health of the patient, and the judgment of the prescribing physician. The size of the dose will also be determined by the active selected, method of administration, timing and frequency of administration, the existence, nature, and extent of any adverse side effects that might accompany the administration of a particular active, and the desired physiological effect. It will be appreciated by one of skill in the art that various diseases or disorders could require prolonged treatment involving multiple administrations, perhaps using one or more modified Tregs in each or various rounds of administration. The term “hinge”, “spacer”, or “linker” refers to an amino acid sequence of variable length typically encoded between two or more domains or portions of a polypeptide construct to confer flexibility, improved spatial organization, proximity, etc. As used herein, "human antibody" means an antibody having an amino acid sequence corresponding to that of an antibody produced by a human and / or which has been made using any of the techniques for making human antibodies known to those skilled in the art or disclosed herein. This definition of a human antibody includes antibodies including at least one human heavy chain polypeptide or at least one human light chain polypeptide. One such example is an antibody including murine light chain and human heavy chain polypeptides. Human antibodies can be produced using various techniques known in the art. In one embodiment, the human antibody is selected from a phage library, where that phage library expresses human antibodies (Vaughan et al., Nature Biotechnology, 14:309-314, 1996; Sheets et al., Proc. Natl. Acad. Sci. (USA) 95:6157-6162, 1998; Hogeboom and Winter, J. Mol. Biol., 227:381, 1991; Marks et al., J. Mol. Biol., 222:581, 1991). Human antibodies can also be made by immunization of animals into which human immunoglobulin loci have been transgenically introduced in place of the endogenous loci, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. This approach is described in U.S. Pat. Nos.5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016. Alternatively, the human antibody may be prepared by immortalizing human B lymphocytes that produce an antibody directed against a target antigen (such B lymphocytes may be recovered from an individual or from single cell cloning of the cDNA, or may have been immunized in vitro). See, e.g., Cole et al., “Monoclonal Antibodies and Cancer Therapy”, Alan R. Liss, p.77, 1985; Boerner et al., J. Immunol., 147 (1):86-95, 1991; and U.S. Pat. No.5,750,373. As used herein, the term "humanized antibody" refers to an immunoglobulin including a human framework region and one or more CDR's from a non-human (usually a mouse or rat) immunoglobulin. The non-human immunoglobulin providing the CDR's is called the "donor" and the human immunoglobulin, providing the framework is called the "acceptor." Constant regions 2945733510.1 need not be present, but if they are, they should be substantially identical to human immunoglobulin, constant regions, i.e., at least about 85-99%, preferably about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDR's, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A humanized antibody is an antibody including a humanized light chain and a humanized heavy chain immunoglobulin. For example, a humanized antibody would not encompass a typical chimeric antibody, because, e.g., the entire variable region of a chimeric antibody is non-human. As used herein, the term "derivative" refers to an antibody or antigen-binding fragment thereof that immunospecifically binds to the same target of a parent or reference antibody but which differs in amino acid sequence from the parent or reference antibody or antigen binding fragment thereof by including one, two, three, four, five or more amino acid substitutions, additions, deletions or modifications relative to the parent or reference antibody or antigen binding fragment thereof. Preferably such derivatives will have substantially the same immunospecificity and / or characteristics, or the same immuno-specificity and characteristics as the parent or reference antibody or antigen binding fragment thereof. The amino acid substitutions or additions of such derivatives can include naturally occurring (i.e., DNA-encoded) or non-naturally occurring amino acid residues. The term "derivative" encompasses, for example, chimeric or humanized variants, as well as variants having altered CH1, hinge. An “iCAR” is a chimeric antigen receptor which contains inhibitory receptor signaling domains. These domains may be based, for example, on protectin D1 (PD1) or CTLA-4 (CD152). In some embodiments, the modified Tregs as discussed herein may be further transduced to express an iCAR. As used herein, "immune cell" refers to a cell of hematopoietic origin functionally involved in the initiation and / or execution of innate and / or adaptive immune response. The term “internal ribosome entry site” or “IRES” refers to a cis-acting RNA sequence that mediates internal entry of the 40S ribosomal subunit on some eukaryotic and viral messenger RNAs. IRES allows for translation initiation in a 5’ cap independent manner during protein synthesis, thus enabling co-expression of two proteins from a single mRNA. Further details and variations of IRES sequences may be found in Bonnal et al., Nucleic Acids Res.2003 Jan 1; 31(1): 427-428. An "intracellular signaling domain” or "ICS domain" as the term is used herein, refers to an intracellular portion of a molecule. The intracellular signaling domain generates a signal that promotes an immune regulatory and / or effector function of the cell transduced with a nucleic acid sequence including a CAR, e.g., a modified Treg including one or more CARs. Examples of immune effector function include cytolytic activity and helper activity, including the secretion of 3045733510.1 cytokines. Example of immune regulatory function, e.g., in a modified Treg, include, but are not limited to including, ICS domains include, but are not limited to including, CD28-CD3zeta; 4-1BB- CD3 zeta; Dap10-CD3zeta; CD44-CD3zeta; CTLA-4-CD3zeta; CD28; Dap10; 4-1BB; 3-zeta. Further examples include an ICS domain of a TCR / CD3 complex protein, an Fc receptor subunit, an IL-2 receptor subunit, CD3 zeta, FcR γ, FcR β, CD3 γ, CD3 δ, CD3 ε, CD5, CD22, CD79a, CD79b, CD66d, CD278 (ICOS), Fc ε RI, DAP10, or DAP12. The term “DAP10” refers to a protein, which in humans is encoded by the HSCT gene. It may also be referred to as HCST, KAP10, PIK3AP, or hematopoietic cell signal transducer. In some embodiments, DAP10 may have the sequence provided in GenBank Accession No.: Q9UBK5.1. An “isolated” biological component (such as an isolated chimeric antigen receptor or cell or vector or protein or nucleic acid) refers to a component that has been substantially separated or purified away from its environment or other biological components in the cell of the organism in which the component naturally occurs, for instance, other chromosomal and extra-chromosomal DNA and RNA, proteins, and organelles. Nucleic acids and proteins that have been “isolated” include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids and proteins prepared by recombinant technology as well as chemical synthesis. An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. The term "linker" as used in the context of an scFv refers to a peptide linker that consists of amino acids such as glycine and / or serine residues used alone or in combination, to link variable heavy and variable light chain regions together. In one embodiment, the flexible polypeptide linker is a Gly / Ser linker and includes one or more repeats of the amino acid sequence unit Gly-Gly-Gly- Gly-Ser (SEQ ID NO: 292). In one embodiment, the flexible polypeptide linker includes, but is not limited to, (Gly4Ser)3(SEQ ID NO: 113), which is also referred to as G4S X3 (SEQ ID NO: 113). The term "nucleic acid" and "polynucleotide" refer to RNA or DNA that is linear or branched, single or double stranded, or a hybrid thereof. The term also encompasses RNA / DNA hybrids. The following are non-limiting examples of polynucleotides: a gene or gene fragment, exons, introns, mRNA, tRNA, rRNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. A polynucleotide may include modified nucleotides, such as methylated nucleotides and nucleotide analogs, uracil, other sugars and linking groups such as fluororibose and thiolate, and nucleotide branches. The sequence of nucleotides may be further modified after polymerization, such as by conjugation, with a labeling component. Other types of 3145733510.1 modifications included in this definition are caps, substitution of one or more of the naturally occurring nucleotides with an analog, and introduction of means for attaching the polynucleotide to proteins, metal ions, labeling components, other polynucleotides or solid support. The polynucleotides can be obtained by chemical synthesis or derived from a microorganism. The term "gene" is used broadly to refer to any segment of polynucleotide associated with a biological function. Thus, genes include introns and exons as in genomic sequence, or just the coding sequences as in cDNAs and / or the regulatory sequences required for their expression. For example, gene also refers to a nucleic acid fragment that expresses mRNA or functional RNA, or encodes a specific protein, and which includes regulatory sequences. A “pharmaceutically acceptable carrier” or “excipient” refers to compounds or materials conventionally used in immunogenic compositions during formulation and / or to permit storage. The term “promoter”, as used herein, is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence. The term "recombinant" means a moiety, e.g., a polynucleotide with semi-synthetic or synthetic origin which either does not occur in nature or is linked to another polynucleotide in an arrangement not found in nature or it may refer to a cell which is modified to express or not express a polynucleotide normally not expressed or expressed by a corresponding unmodified cell. The term "scFv," “single-chain Fv,” or “single-chain variable fragment” refers to a fusion protein including at least one antibody fragment including a variable region of a light chain and at least one antibody fragment including a variable region of a heavy chain, wherein the light and heavy chain variable regions are contiguously linked, e.g., via a synthetic linker, e.g., a short flexible polypeptide linker, and capable of being expressed as a single chain polypeptide, and wherein the scFv retains the specificity of the intact antibody from which it is derived. Unless specified, as used herein an scFv may have the VLand VHvariable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide, the scFv may include VL-linker- VHor may include VH-linker-VL. The linker may include portions of the framework sequences. The term “sequence identity” or “sequence homology” are used interchangeably herein and both refer to the sequence similarity of different polypeptides or nucleic acids. In general the disclosure contemplates polypeptide or nucleic acids or constructs containing same having at least 90% or greater sequence homology or identity to any one or more of the polypeptide or nucleic acid sequences disclosed herein, more typically polypeptide or nucleic acid sequences having at least 95% or greater sequence homology to any one or more of the polypeptide or nucleic acid sequences disclosed herein or possessing at least 98% or greater sequence homology or sequence identity, or 3245733510.1 at least 99% or greater sequence homology or identity to any one or more of the polypeptide or nucleic acid sequences set forth herein. Methods for determining homology between nucleic acid and amino acid sequences are well known to those of ordinary skill in the art. Generally such homologous nucleic acids or polypeptides will be selected or designed so as to improve or so as to not adversely impact the desired properties of the specific polypeptide or nucleic acid or construct containing same. A “signal peptide” (also referred to as a signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide present at the N-terminus of the majority of newly synthesized proteins that are destined towards the secretory pathway. The core of the signal peptide may contain a long stretch of hydrophobic amino acids. The signal peptide may or may not be cleaved from the mature polypeptide. A “leader sequence” as used herein, also referred to as “signal peptide,” “signal sequence,” “targeting signal,” “localization signal,” “localization sequence,” “transit peptide,” or “leader peptide” in the art, is a short peptide present at the N-terminus of the majority of newly synthesized proteins that are destined towards the secretary pathway. The core of the signal peptide may contain a long stretch of hydrophobic amino acids. The signal peptide may or may not be cleaved from the mature polypeptide. The “ribosome skip sequence” refers to an amino acid sequence that, when translated, causes cleavage of a nascent polyprotein on the ribosome, allowing for co-expression of multiple genes. In one aspect, the ribosome skip sequence may be the T2A sequence and includes the amino acid sequence or nucleotide sequence encoding contained in the Sequence Listing preceding the claims. Alternatively, any other 2A sequences may be used. Examples of other 2A sequences may be found elsewhere in the literature of the relevant art (for example, see Kim, J.H., et al., “High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice” PLoS One.2011;6(4)). The term “signaling domain” refers to the functional portion of a protein which acts by transmitting information within the cell to regulate cellular activity via defined signaling pathways by generating second messengers or functioning as effectors by responding to such messengers. Examples of signaling domains include, but are not limited to including, CD28-CD3ζ; 4-1BB- CD3ζ; Dap10-CD3ζ; CD44-CD3ζ; CTLA-4-CD3ζ; CD28; Dap10; 4-1BB; and CD3-ζ. The term "stimulatory molecule," refers to a molecule expressed by an immune cell (e.g., T cell, NK cell, B cell) that provides the cytoplasmic signaling sequence(s) that regulate activation of the immune cell in a stimulatory way for at least some aspect of the immune cell signaling pathway. In one aspect, the signal is a primary signal that is initiated by, for instance, binding of a TCR / CD3 3345733510.1 complex with an MHC molecule loaded with antigenic peptide, and which leads to mediation of a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like. A primary cytoplasmic signaling sequence (also referred to as a "primary signaling domain") that acts in a stimulatory manner may contain a signaling motif which is known as an immunoreceptor tyrosine-based activation motif or ITAM. Examples of an ITAM containing cytoplasmic signaling sequence include, but are not limited to, those derived from CD3ζ, common FcRγ (FCER1G), FcγRIIa, FcR β (Fc ε R1b), CD3γ, CD3δ, CD3ε, CD79a, CD79b, DAP10, and DAP12. In exemplary embodiments, the intracellular signaling domain in any one or more CARs included by a modified Treg may include an intracellular signaling sequence, e.g., a primary signaling sequence of CD3ζ. Alternatively, equivalent residues from a non-human or mouse species, e.g., rodent, monkey, ape and the like, may be utilized. The term "subject" is intended to include living organisms in which an immune response can be elicited (e.g., mammals, human). The subject may have a disease or may be healthy. The subject may also be referred to as “patient” in the art. The term “suicide mechanism” or “suicide gene” as used herein refers to a mechanism by which CAR-expressing cells of present disclosure may be eradicated from a subject administered with CAR-expressing cells. The suicide mechanism may be driven by, for example, inducible caspase 9 (Budde et al., PLoS One 20138(12):82742), codon-optimized CD20 (Marin et al., Hum. Gene Ther. Meth.201223(6)376-86), CD34, a truncated EGFR (Wang X, Chang W-C, Wong CW, et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood.2011;118(5):1255-1263. doi:10.1182 / blood-2011-02-337360), a truncated CD19, or polypeptide RQR8 (Philip et al, and WO2013153391A, which is hereby incorporated herein by reference). In some embodiments, the suicide mechanism may be included and utilized in modified Tregs discussed herein to optimize the length for the modified Tregs to stay in the system of a subject or the amount of the modified Tregs, to reduce or minimize the toxicity and / or to maximize the benefit of the modified Tregs. The term “synthetic immune receptor” or “SIR” as used herein refers to a non-naturally occurring set of polypeptides, typically two in the some embodiments, which when expressed in an effector cell (e.g., Treg) provides the cell with specificity for a target molecule of interest and / or a target cell expressing such target molecule of interest and with intracellular signal generation. In some embodiments, a SIR includes one or more antigen recognition domains (e.g., antibody or antibody fragment, a ligand or a receptor, etc.) that bind to a target molecule of interest, and are joined to one or more T cell receptor (TCR) constant chains or regions via an optional linker. In certain embodiments, the set of polypeptides are contiguous with each other. In certain 3445733510.1 embodiments, a SIR includes two or more sets of two or more polypeptides. The polypeptides of each set of SIR are contiguous with each other (functional polypeptide unit 1) but are not contiguous with the polypeptides of the other set (functional polypeptide unit 2). In some cases, the TCR constant chains (or regions) of the SIR is chosen from the constant chain of human T cell receptor-alpha (TCR-alpha or TCRα or TCRa or hTCR-alpha or hTCRα or hTCRa or Cα), human T cell receptor-beta1 (TCR-beta1 or TCRβ1 or TCRb1 or hTCR-beta1 or hTCRβ1 or hTCRb1 or Cβ1), human T cell receptor-beta 2 (TCR-beta2 or TCRβ2 or TCRb2 or hTCR-beta2 or hTCRβ2 or hTCRb2 or Cβ2 also designated TCR-beta, TCRβ or TCRb or Cβ), human Pre-T cell receptor alpha (preTCR-alpha or preTCRα or preTCRa or preCα), human T cell receptor-gamma (TCR-gamma or TCRγ or TCRg or hTCR-gamma or hTCRγ or hTCRg or hTCRγ1 or hTCRgamma1, or Cγ), or human T cell receptor-delta (TCR-delta or TCRd or TCRδ or hTCR-delta or hTCRd or hTCRδ or Cδ). In some embodiments, the TCR constant chains of SIR are encoded by their wild-type nucleotide sequences while in other embodiments the TCR constant chains of SIR are encoded by the nucleotide sequences that are not wild-type. For example, for use in humans, it may be beneficial for the TCR constant chain of the SIR to be derived from or included of human TCR constant chains. Exemplary SIRs include but not limited to those described in US20220204582A1 and US20210137977A1. The term “target cell” as used herein refers to a cell expressing the target molecule of a CAR included by a modified Treg on the cell surface. In some embodiments, the target cell is a microglia cell. In some embodiments, the target cell is a neuron. In some embodiments, the target cell is a cell type that has a particular role in the pathology of a neurodegenerative disease and / or condition and / or neuroinflammation. In some embodiments, the target cell is a cell type that has a particular role in the pathology of a disease such as but not limited to Alzheimer’s disease, Parkinson’s disease, ALS, and any of the other neurodegenerative diseases and conditions discussed herein. The term “target molecule” as used herein refers to a molecule that is targeted by a CAR or a cell which expresses same such as a modified Treg, e.g., a modified Treg including one or more CARs, of the present disclosure. The AB domain of a CAR included by a modified Treg of the present disclosure may have a binding affinity for the target molecule. In some embodiments, the target molecule is a form of amyloid-beta 1-42 associated with a neurodegenerative disease or condition. In some embodiments, the target molecule is a form of alpha-synuclein associated with a neurodegenerative disease or condition. In some embodiments, the target molecule is a form of superoxide dismutase-1 (SOD-1) associated with a neurodegenerative disease or condition. In some embodiments, the target molecule may be, but is not limited to being, forms of any of the following associated with a neurodegenerative disease and / or condition: hyperphosphorylated tau protein; 3545733510.1 TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; ataxins; P / Q-type calcium channel α1A subunit; TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C. In some embodiments, the target molecule may be a molecule associated with any of the following non-limiting list of neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, ALS, prion disease, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. The term "transfected," "transformed," or "transduced" refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A "transfected" or "transformed" or "transduced" cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. By the term “transmembrane domain” or “TM domain”, what is implied is any three- dimensional protein structure which is thermodynamically stable in a membrane. This may be a single α helix, a transmembrane β barrel, a β-helix of gramicidin A, or any other structure. Transmembrane helices are usually about 20 amino acids in length. Typically, the transmembrane domain denotes a single transmembrane α helix of a transmembrane protein, also known as an integral protein. As used herein, the terms "treat," "treatment," or "treating" generally refers to a clinical procedure for reducing or ameliorating the onset, progression, severity, and / or duration of a disease 3645733510.1 and / or condition, or for ameliorating one or more symptoms (preferably, one or more discernible symptoms) of a disease and / or condition. The disease may be, for example, a neurodegenerative disease or condition. In some embodiments, the effect of the “treatment” may be evaluated by the amelioration of at least one measurable physical parameter of a disease, resulting from the administration of one or more therapies (e.g., one or more therapeutic agents such as a modified Treg as described herein). The parameter may be, for example, gene expression profiles, the mass of disease-affected tissues, inflammation-associated markers, neurodegenerative disease-associated markers, the presence or absence of certain cytokines or chemokines or other disease-associated molecules, and may not necessarily discernible by the patient. In other embodiments "treat", "treatment," or "treating" may result in the inhibition of the progression of a disease and / or condition, either physically by, e.g., stabilization of a discernible symptom, physiologically by, e.g., stabilization of a physical parameter, or both. Additionally, the terms “treat,” and “prevent” as well as words stemming therefrom, as used herein, do not necessarily imply 100% or complete cure or prevention. Rather, there are varying degrees of treatment effects or prevention effects of which one of ordinary skill in the art recognizes as having a potential benefit or therapeutic effect. In this respect, the inventive methods can provide any amount of any level of treatment or prevention effects of a disease and / or condition in a mammal. Furthermore, the treatment or prevention provided by the methods described herein can include treatment or prevention of one or more conditions or symptoms of the disease being treated or prevented. Also, for purposes herein, “prevention” can encompass delaying the onset of the disease, or a symptom or condition thereof. The term "xenogeneic" refers to a graft derived from an animal of a different species. As used herein, the term “recombinant Tregs” or “modified Tregs” generally refers to a regulatory T cell that has been altered relative to its native state, e.g., genetically modified. For example, in exemplary embodiments, a modified Treg may be engineered to express one or more CARs. Additionally, exemplary modified Tregs may be engineered to express one or more NDMMs. Modified Tregs according to the disclosure may be used to treat various diseases in exemplary embodiments. For example, modified Tregs may be used in methods of treating specific neurodegenerative diseases, conditions, or disorders. Exemplary neurodegenerative diseases, conditions, and / or disorders that may be treated with modified Tregs as disclosed herein include by way of example ALS, Alzheimer’s disease, and Parkinson’s disease. Furthermore, in exemplary embodiments the modified Tregs of the present disclosure may be used to treat neuroinflammation in the CNS. In some embodiments, the modified Tregs of the present disclosure may be used to treat any of the following non-limiting list of neurodegenerative diseases and / or conditions: Alzheimer’s disease, Parkinson’s disease, ALS, prion disease, motor neuron diseases other than 3745733510.1 ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. Disclosed are materials, compositions, and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed method and compositions. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a ligand is disclosed and discussed and a number of modifications that can be made to a number of molecules including the ligand are discussed, each and every combination and permutation of ligand and the modifications that are possible are specifically contemplated unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, in this example, each of the combinations A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E are specifically contemplated and should be considered disclosed from disclosure of A, B, and C; D, E, and F; and the example combination A-D. Further, each of the materials, compositions, components, etc. contemplated and disclosed as above can also be specifically and independently included or excluded from any group, subgroup, list, set, etc. of such materials. These concepts apply to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional 3845733510.1 steps that can be performed it is understood that each of these additional steps can be performed with any specific form or combination of forms of the disclosed methods, and that each such combination is specifically contemplated and should be considered disclosed. All methods described herein can be performed in any suitable order unless otherwise indicated or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the forms and does not pose a limitation on the scope of the forms unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Use of the term “about” is intended to describe values either above or below the stated value in a range of approx. + / - 10%; in other forms the values can range in value either above or below the stated value in a range of approx. + / - 5%; in other forms the values can range in value either above or below the stated value in a range of approx. + / - 2%; in other forms the values can range in value either above or below the stated value in a range of approx. + / - 1%. The preceding ranges are intended to be made clear by context, and no further limitation is implied. II. COMPOSITIONS OF MODIFIED REGULATORY T CELLS (MTREGS) The present disclosure provides modified regulatory T Cells, e.g., Tregs engineered to express which includes a DNA construct encoding (1) a chimeric antigen receptor (CAR), (2) a DNA encoding at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA); and (3) optionally a DNA construct encoding a “neurodegenerative disease-modifying molecule” or “NDMM” or “disease- modifying molecule” or DMM; wherein (i) the DNA encoding (1) and (2) and (3) may be on the same or different constructs; (ii) expression of the DNA encoding (1) and (2) and optionally (3) may be controlled by the same or different inducible or constitutive promoters; (iii) the Treg including the DNA (1) and (2) and optionally (3) inducibly or constitutively expresses at least one of IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); the CAR and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the Treg persists longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen compared to a Treg which includes a 3945733510.1 DNA construct encoding the same (1) chimeric antigen receptor (CAR) but which does not include (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B- CA) or constitutively active STAT5A (STAT5A-CA). The present disclosure also provides DNA constructs encoding (1) a chimeric antigen receptor (CAR), (2) a DNA encoding at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); and (3) optionally a DNA construct encoding a “neurodegenerative disease-modifying molecule” or “NDMM” or “disease-modifying molecule” or DMM; wherein (i) expression of the DNA encoding (1) and (2) and optionally (3) may be controlled by the same or different inducible or constitutive promoters; (ii) the DNA construct when introduced in to a Treg inducibly or constitutively expresses at least one of IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); the CAR and optionally a DMM or NDMM when introduced into a subject in need thereof; (iii) the DNA construct when introduced in to a Treg persists longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen compared to a Treg which includes a DNA construct encoding the same (1) chimeric antigen receptor (CAR) but which does not include (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA). The present disclosure also provides methods of using the modified Tregs and compositions containing, in particular for treating a disease, disorder, or condition, e.g., neurodegenerative diseases, disorders, or conditions. In exemplary embodiments, these modified Tregs are engineered to express on their surface at least one moiety, e.g., an antibody and typically an scFv which recognizes a protein the expression of which is associated with a specific neurodegenerative condition, e.g., specific molecular markers of a particular neurodegenerative disease or condition, such as, for example, proteins and / or molecular markers associated with neuroinflammation, ALS, Alzheimer’s disease, and / or Parkinson’s disease. In other exemplary embodiments, modified Tregs are engineered to express or further express specific molecules that prevent oxidative / inflammatory activity and / or which promote neuronal growth, function and / or survival such as anti-oxidants, nerve growth factors and non-classical neurotrophic growth factors. In exemplary embodiments, modified Tregs according to the disclosure will maintain Treg phenotype and / or maintain at least one Treg effector function, and ideally will retain substantially all effector functions possessed by unmodified Tregs and will persist in the CNS and / or spleen for prolonged duration. 4045733510.1 In exemplary embodiments the modified Tregs are human or murine, and express a CAR which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of inflammation or autoimmunity, and typically to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition. In exemplary embodiments the modified Tregs are human or murine, and express a CAR which binds to an antigen, ligand or receptor which is aberrantly or over expressed in a subject having a neurodegenerative or neuroinflammatory selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral- pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis and preferably Alzheimer’s disease, or ALS. In exemplary embodiments the modified Tregs express a CAR which includes an scFv or ligand which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of inflammation or autoimmunity, or the CAR includes an scFv or ligand which binds to an antigen, ligand or receptor which is aberrantly or over expressed at a site of neurodegeneration or neuroinflammation. In exemplary embodiments the modified Tregs express a CAR which binds to an antigen, ligand or receptor which is aberrantly or over expressed the CAR specifically binds to an antigen selected from amyloid-beta 1-42, alpha-synuclein, superoxide dismutase-1 (SOD-1), hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43): chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), an antigen including Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel 4145733510.1 α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; cystatin C; or optionally to an amyloid protein, further optionally amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS. In exemplary embodiments the modified Tregs includes a DNA construct encoding at least one NDMM or DMM, optionally selected from IL-37, IL-12, TNF-α, IFN-γ, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease- associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin. Examples of nerve growth factors include, but are not limited to, classic neurotrophins such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G-CSF), and in exemplary embodiments includes a DNA construct encoding a NDMM or DMM selected from BDNF or IGF-1. In exemplary embodiments the modified Tregs express a CAR which binds to an antigen, ligand or receptor which is aberrantly or over expressed wherein the CAR, IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); and DMM coding sequences, optionally BDNF or IGF-1 are oriented from 5’ to 3’ orientation in the CAR construct as follows: A. Nucleic Acid Constructs Encoding CAR-IL2-DMM Nucleic acid construct(s) encoding a CAR, at least one or more of intact mature human Interleukin-2 (IL2), or a functional derivative or variant thereof, and a disease modifying molecule (DMM), and the fusion proteins expressed therefrom are provided. In some forms, a single polycistronic nucleic acid encodes a CAR, at least one or more of intact mature human Interleukin- 2 (IL2), or a functional derivative or variant thereof, and a disease modifying molecule (DMM). In other forms, the CAR, at least one or more of intact mature human Interleukin-2 (IL2), or a 4245733510.1 functional derivative or variant thereof, and / or the disease modifying molecule (DMM) are encoded by separate nucleic acids. In some exemplary embodiments the CAR DNA construct included in the modified Tregs includes at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4-CD3ζ, CD28, DAP10, 4-1BB, CD3ζ, and CD44, and optionally is selected from CD28-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CD28 and CD3ζ. In some exemplary embodiments the CAR on the DNA construct included in the modified Tregs is associated with the transmembrane (TM) region of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD44, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof. In some exemplary embodiments the modified Tregs includes a suicide gene, optionally on the CAR construct, further optionally expressed under the control of an inducible promoter. In some exemplary embodiments the DNA construct included in the modified Tregs includes a retroviral construct, further optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct, that optionally includes an IL-2 minimal promoter and NFAT binding sites. In some exemplary embodiments the CAR DNA construct included in the modified Tregs the DNA construct which encodes the CAR includes (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain. In some exemplary embodiments the CAR DNA construct included in the modified Tregs includes (1) a DNA encoding an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) a DNA encoding human IL-2 or a human IL-2 mutein, and (3) a DNA encoding BDNF or IGF-1. In some exemplary embodiments the CAR DNA construct included in the modified Tregs t is selected from JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z- T2A-hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A-mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5b-CA; DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5a- CA having the sequences in the informal Sequence Listing preceding the claims and / or includes a CAR DNA construct as schematically depicted in Figure 1 or Figure 2. 4345733510.1 In some exemplary embodiments the CAR DNA construct included in the modified Tregs includes a nucleic acid sequence encoding an antigen binding domain including the heavy and light chain variable region CDRs and optionally the entire heavy and light chain variable regions of DG01, DG02, DG03, DG04, DG05, DG06, DG07, DG08, DG09, DG10 or DG11, and preferably includes DG03 or DG05, having the sequences contained in the informal Sequence Listing preceding the claims. In some exemplary embodiments modified Tregs according to the disclosure may migrate or traffic to the site of neurodegeneration and / or neuroinflammation. In further exemplary embodiments, modified Tregs according to the disclosure may lead to an anti-inflammatory activity at a site of neurodegeneration and / or neuroinflammation. The activities may include any activities which are associated with neurodegeneration and / or neuroinflammation, such as, for example, (1) microglia cell over-activation, (2) production of inflammatory proteins / activities, and (3) neuronal death. Exemplary methods of treatment including modified Tregs may result in reduced disease progression and / or may repair and / or improve function in a patient in need thereof. In some embodiments, Tregs may be isolated from donor PBMCs and expanded for use, e.g., clinical use. In some exemplary embodiments the donor cells may be allogeneic. In other exemplary embodiments the donor PBMCs used to derive Tregs may be isolated from the same subject who is to be treated. In some exemplary embodiments the isolated Tregs may be modified to reduce or eliminate the expression or functionality of the endogenous TCR. In some exemplary embodiments the isolated Tregs may be combined with Tregs isolated from different donors which donors may be MHC compatible or incompatible. In some embodiments, Tregs may be expanded by up to a 550-fold increase in number, in some instances in a two week period of culturing. In other exemplary embodiments, the Tregs will include a purity of 90% or greater. In other exemplary embodiments, modified Tregs may cross the blood-brain barrier (BBB). In some embodiments, Tregs may be isolated, expanded, and transduced as follows: cells may be isolated from human PBMCs via a two-step negative and positive selection protocol. First, CD4+cells are isolated using negative selection, followed by a positive selection of CD25hi+cells to isolate CD4+CD25hi+Treg cells or by cell sorting CD25hi,CD127locells to isolate CD4+CD25hiCD127loTreg cells. These isolated Tregs may be activated with anti-CD3, anti-CD28, and anti-CD2 multimers or anti-CD3, and anti-CD28 multimers (STEMCELL ImmunoCult) with human IL-2 (300U / ml to 500 U / ml) over two weeks in culture in Treg growth medium. On day 7-9, Treg cells can be cryopreserved for use at a later date. This also allows for the test of the same donor and preparation on multiple occasions to assess assay variability. 4445733510.1 1. Chimeric Antigen Receptor (CAR) Components In further exemplary aspects, modified Tregs may be modified to express one or more CARs, preferably expressed on their cell surface. i. CAR structure CARs are engineered receptors that possess both antigen-binding and T cell-activating functions. Immunotherapy using T cells genetically engineered to express a CAR is rapidly emerging as a promising new treatment for hematological and non- hematological malignancies. Based on the location of the CAR in the membrane of the cell, the CAR can be divided into three main distinct domains, including an extracellular antigen-binding domain, followed by a space region, a transmembrane domain, and the intracellular signaling domain. The antigen-binding domain, most commonly derived from variable regions of immunoglobulins, typically contains VH and VL chains that are joined up by a linker to form the so called “scFv.” The segment interposing between the antigen-binding domain (e.g., scFv) and the transmembrane domain is a “spacer domain.” The spacer domain can include the constant IgG1 hinge CH2–CH3 Fc domain. In some cases, the spacer domain and the transmembrane domain are derived from CD8. The intracellular signaling domains mediating T cell activation can include a CD3ζ co receptor signaling domain derived from C region of the TCR α and β chains and one or more costimulatory domains. In some forms, conjugation with one or more CT domains includes addition of the one or more CT domains immediately next to the costimulatory domains of the CAR. a. CAR Antigen Binding Domain In some forms, the antigen-binding domain is derived from an antibody. The term antibody herein refers to natural or synthetic polypeptides that bind a target antigen. The term includes polyclonal and monoclonal antibodies, including intact antibodies and functional (e.g., antigen- binding) antibody fragments, including Fab fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rlgG) fragments, single chain antibody fragments, including single chain variable fragments (scFv), and single domain antibodies (e.g., sdAb, sdFv, nanobody) fragments. The term encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, e.g., bispecific, antibodies, diabodies, triabodies, and tetrabodies, tandem di scFv, tandem tri scFv. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and sub classes thereof, IgM, IgE, IgA, and IgD. The antigen-binding domain of a CAR can contain complementary determining regions (CDR) of an antibody, variable regions of an antibody, and / or 4545733510.1 antigen binding fragments thereof. In some forms, the antigen-binding domain can include an F(ab')2, Fab', Fab, Fv or scFv. Exemplary CARs according to the disclosure may include a ligand binding moiety such as a receptor or an antibody, e.g., an scFv which recognizes proteins and / or other molecular markers associated with diseases and / or conditions which are to be treated using the Tregs, for example, particular neurodegenerative diseases and / or neuroinflammation. In some embodiments of the disclosure these CARs may further include one or more costimulatory signaling or T cell signaling moieties or domains such as are identified herein and exemplified in the working examples or others which are generally known in the art. Exemplary neurodegenerative diseases characterized by the expression of aberrant proteins or aberrantly expressed proteins which are associated with disease pathology that may be recognized by CARs expressed by modified Tregs according to the disclosure include by way of example ALS, Alzheimer’s disease, and Parkinson’s disease. When expressed in modified Tregs, one or more CARs as described herein may trigger effector responses, such as, for example, cytokine expression. In exemplary embodiments, the CAR may trigger effector responses in the presence of one or more specific antigens. Moreover, in some aspects, modified Tregs may include one or more CARs, and the one or more CARs may trigger IL-10 production upon stimulation, e.g., stimulation by a specific antigen. In further exemplary embodiments, modified Tregs may include one or more CARs, and the modified Tregs may retain their ability to suppress other T cells. In some embodiments, modified Tregs may include one or more CARs, and the modified Tregs may be in subsets of T cells with known regulatory and / or anti-inflammatory activity, such as, for example, FOXP3+Tregs. In exemplary embodiments, modified Tregs may include one or more CARs, wherein the one or more CARs include single chain variable fragments (scFv) that may be targeted to a protein and / or molecular marker of a disease, transmembrane signaling domain, and cytoplasmic signaling domain. In exemplary embodiments, modified Tregs including one or more CARs targeted to a disease of interest may result in greater inhibition of inflammatory cytokine production, higher expression of anti- inflammatory cytokines, greater protection against neuroinflammation-mediated motor neuron death, and improve survival as compared to control treatments. In some embodiments, a modified Treg may include one or more CARs as described herein, wherein the sequence that encodes the CARs may include a signal sequence. It is to be understood that the signal sequence may or may not be cleaved during expression of the CAR. In some embodiments, a modified Treg may include one or more CARs that target a form of amyloid-beta associated with a neurodegenerative disease or condition. In some embodiments, a modified Treg may express a DNA construct encoding one or more CARs having the sequences (e.g., DG01- 4645733510.1 DG11, DG15, DG16) contained in the Sequence Listing preceding the claims, or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. The AB domain may be derived from a polypeptide that binds to a target molecule. In some embodiments, the polypeptide may be a receptor or a portion of a receptor that binds to a target molecule. In another embodiment, the AB domain may be derived from a ligand that binds to the target molecule. In another embodiment, the AB domain may be derived from an antibody (Ab) or antigen- binding fragment thereof that binds to a target molecule. Examples of an Ab or antigen-binding fragment thereof include, but are not limited to, a monoclonal Ab, a monospecific Ab, a polyspecific Ab, a humanized Ab, a tetrameric Ab, a tetravalent Ab, a multispecific Ab, a single chain Ab, a domain-specific Ab, a single-domain Ab (dAb), a domain-deleted Ab, an scFc fusion protein, a chimeric Ab, a synthetic Ab, a recombinant Ab, a hybrid Ab, a mutated Ab, CDR-grafted Ab, an Ab fragment including a fragment antigen-binding (Fab), an F(ab’)2, an Fab’ fragment, an variable fragment (Fv), a single-chain antibody fragment, a single-chain Fv (scFv) fragment, an Fd fragment, a dAb fragment, a diabody, a nanobody, a bivalent nanobody, a shark variable IgNAR domain, a VHH Ab, a camelid Ab, and a minibody. In a particular embodiment, the AB domain includes a single-chain antibody fragments including a variable heavy chain region and / or a variable light chain region, such as scFv. In another particular embodiment, the AB domain includes a nanobody. Single-domain Abs are Ab fragments including all or a portion of the heavy chain variable domain or all or a portion of the light chain variable domain of an antibody. In certain embodiments, a single-domain antibody is a human single-domain antibody. Antibody fragments can be made by various techniques, including but not limited to proteolytic digestion of an intact Ab as well as production by recombinant host cells. In some embodiments, the antibodies are recombinantly produced fragments, such as fragments including arrangements that do not naturally occur, such as those with two or more Ab regions or chains joined by synthetic linkers, such as peptide linkers, and / or that may not be produced by enzyme digestion of a naturally occurring intact Ab. In some aspects, the Ab fragments are scFvs. In some aspects, the Ab fragments are nanobodies. In some aspects, the AB domain may be derived from an Ab or an antigen-binding fragment thereof that has one or more specified functional features, such as binding properties, including binding to particular epitopes, such as epitopes that are similar to or overlap with those of other Abs. 4745733510.1 In some embodiments, the AB includes an scFv including CDR sequences of an Ab specific to the target molecule. CDRs may be determined using conventional methods. The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (“Kabat” numbering scheme), Al-Lazikani et al., “ (1997) J. Mol. Biol.273, 927-948 (“Chothia” numbering scheme), MacCallum et al., J. Mol. Biol.262:732-745 (1996), “Antibody- antigen interactions: Contact analysis and binding site topography,” J. Mol. Biol.262, 732-745 (“Contact” numbering scheme), Lefranc M P et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol, 2003 January; 27(1):55-77 (“IMGT” numbering scheme), and Honegger A and Pluckthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol, 2001 Jun.8; 309(3):657-70, (“Aho” numbering scheme). In some embodiments, the sequence including the AB domain further includes a leader sequence or signal sequence. In some embodiments where the AB domain includes an scFv, the leader sequence may be positioned at the amino terminus of the scFv. In some embodiments where the heavy chain variable region is N-terminal, the leader sequence may be positioned at the amino terminus of the heavy chain variable region. In some embodiments where the light chain variable region is N-terminal, the leader sequence may be positioned at the amino terminus of the light chain variable region. The leader sequence may include any suitable leader sequence. In the mature form of the isolated cells of the disclosure, the leader sequence may not be present. In exemplary embodiments, the described modified Tregs include one or more CARs targeted to a neurodegenerative disease or condition, as discussed above and below. In some exemplary embodiments, one or more CARs may include an AB domain that binds to a target molecule which is associated with a neurodegenerative disease or condition. AB domains are discussed further below. In preferred embodiments, a CAR may target a protein or a mutant version of a protein including a sequence selected from Human amyloid beta, isoform APP770 (identifier: P05067-1); human superoxide dismutase (human superoxide dismutase, identifier: P00441-1, wild type sequence) or human alpha-synuclein, Isoform 1 (identifier: P37840-1). In some embodiments, a CAR may target a molecular marker, e.g., a protein, associated with any one or more of the following neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, ALS, prion disease, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy 4845733510.1 body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. In some exemplary embodiments, a CAR included by a modified Treg may target amyloid beta 1-42. In other exemplary embodiments, a CAR included by a modified Treg may target superoxide dismutase-1 (SOD-1). In other exemplary embodiments, a CAR included by a modified Treg may target alpha-synuclein. In other exemplary embodiments, a CAR included by a modified Treg may target any of the following non-limiting list: hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43);phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2). In some embodiments, a CAR included by a modified Treg may target any one or more of the following: Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; ataxins; P / Q-type calcium channel α1A subunit; TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; cystatin C. Exemplary antigen binding domains are available in US patent application publication Nos.20150315267 A1 (Aducanumab; BIIB037), US 20150246963 A1 (Crenezumab; MABT5102A), US 2014 / 0369940 A1 (NI-202.21D11); and in US patent nos.8,613,920 (Bapineuzumab; AAB001), 9109037 (clone 595-16-M1; 16L40, and clone 358-11-M1; 11L80, and clone 597-120-M1; 120c), 8,940,276 (NI-202.3G120, and NI-202.12F4), 8,632,776 (mAb49 / G), 8,679,498 (Donanemab); and in international patent application publication WO 2024054416A (Lecanemab), the contents of which are incorporated by reference herein in their entirety See also, US Published Application No.2021 / 0015861 and WO 2019 / 157440, which are specifically incorporated by reference herein in their entries 4945733510.1 . (1) Amyloid Proteins In exemplary embodiments the CAR is one which binds to an amyloid expressed in Alzheimer’s disease. Exemplary antigen binding domains that bind to amyloid expressed in Alzheimer’s disease include those isolated from hybridomas DG01, DG02, DG03, DG04, DG15, and DG16 implemented within single chain Fv constructs, including a leader sequence, a heavy chain Fv immunoglobulin domain, a linker, and a light chain Fv domain, and having the following amino acid sequence (with the font annotated to show the residues in each of leader sequence ; heavy chain framework ; heavy chain CDR1 ; heavy chain framework; heavy chain CDR2 ; heavy chain framework; heavy chain CDR3 ; heavy chain framework; linker sequence, light chain framework ; light chain CDR1 ; light chain framework ; light chain CDR2 ; light chain framework ; light chain CDR3 ; and light chain framework, respectively): DG01 scFv (SEQ ID NO: 101) MEWTWVFLFLLSVTAGVHSQVQLVESGGGVVQPGRSLRLSCAASGFAFSSYGMHWVRQAPGKGLEW VAVIWFDGTKKYYTDSVKGRFTISRDNSKNTLYLQMNTLRAEDTAVYYCARDRGIGARRGPYYMDV PGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVE IK DG02 scFv (SEQ ID NO: 102) MEWTWVFLFLLSVTAGVHSEVQLLESGGGLVQPGGSLRLSCAASGFTFSNYGMSWVRQAPGKGLEW VASIRSGGGRTYYSDNVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVRYDHYSGSSDYWGQGT LVTVSSAGGGGSGGGGSGGGGSDVVMTQSPLSLPVTPGEPASISCKSSQSLLDSDGKTYLNWLLQK PGQSPQRLIYLVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTHFPRTFGQGTKVE IK DG03 scFv (SEQ ID NO: 103) MEWTWVFLFLLSVTAGVHSEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYGMSWVRQAPGKGLEL VASINSNGGSTYYPDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCASGDYWGQGTTVTVSSA GGGGSGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLVYSNGDTYLHWYLQKPGQSPQL LIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHVPWTFGQGTKVEIK 5045733510.1 DG04 scFv (SEQ ID NO: 104) MEWTWVFLFLLSVTAGVHSQVELVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEW VSAINASGTRTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGKGNTHKPYGYVRYF DVWGQGTLVTVSSAGGGGSGGGGSGGGGSDIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWY QQKPGQAPRLLIYGASSRATGVPARFSGSGSGTDFTLTISSLEPEDFATYYCLQIYNMPITFGQGT KVEIK Assembled DG15 scFv Amino Acid Sequence (SEQ ID NO: 159) MEWTWVFLFLLSVTAGVHSEVQLVESGGGLVQPGGSLRLSCSASGFTFSSFGMHWVRQAPGKGLEW VAYISSGSSTIYYGDTVKGRFTISRDNAKNSLFLQMSSLRAEDTAVYYCAREGGYYYGRSYYTMDY WGQGTTVTVSSAGGGGSGGGGSGGGGSDVVMTQSPLSLPVTPGAPASISCRSSQSIVHSNGNTYLE WYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLRISRVEAEDVGIYYCFQGSHVPPTFGP GTKLEIK Assembled DG16 scFv Amino Acid Sequence (SEQ ID NO: 165) MEWTWVFLFLLSVTAGVHSQVQLVQSGAEVKKPGSSVKVSCKASGYDFTRYYINWVRQAPGQGLEW MGWINPGSGNTKYNEKFKGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGITVYWGQGTTVTV PQLLIYAVSKLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCVQGTHYPFTFGQGTKLEIK In some forms, the antigen binding domain of the CAR includes six CDRs. The CDRs can include at least one, two, three, four, five or six consensus CDRs of the CDRs of anti-amyloid antibody, such as those provided herein, e.g., DG01, DG02, DG03, DG04, DG15, and DG16. The antigen binding domains also typically include heavy chain and light chain variable domains. For example, in some forms, the antigen binding domain contains at least one, two, three, four, five or six CDRs of the heavy and / or light chain variable domains, and / or the entire heavy and / or light chain variable domains of any one of SEQ ID NOS:101-104, 159, or 165, or a variant thereof with at least 70%, 75%, 80%, 85%, 90%, or 95% sequence identity to the CDRs and / or entire heavy and light variable domains of SEQ ID NOS:101-104, 159, or 165, optionally wherein there is 6, 5, 4, 3, 2, 1, or 0 in one, two, three, four, five, or all six of CDRs of SEQ ID NOS:101- 104, 159, or 165. Thus, in some forms, there is variation in one or more CDRs and / or the heavy chain variable domain and / or the light chain variable domain. In other embodiments the is variation in the heavy chain variable domain and / or the light chain variable domain, but not in the CDRs relative to the heavy chain variable domain and / or the light chain variable domain. 5145733510.1 (2) SOD-1 In other exemplary embodiments the CAR is one which binds to SOD-1, for example, expressed during ALS. Exemplary antigen binding components that bind to SOD-1 expressed during ALS disease is that isolated from hybridomas DG05, DG06, and DG07 having the following amino acid sequences (with the font annotated to show the residues in each of leader sequence ; heavy chain framework ; heavy chain CDR1 ; heavy chain framework; heavy chain CDR2 ; heavy chain framework; heavy chain CDR3 ; heavy chain framework; linker sequence, light chain framework ; light chain CDR1 ; light chain framework ; light chain CDR2 ; light chain framework ; light chain CDR3 ; and light chain framework, respectively): DG05 scFv (SEQ ID NO: 105) MEWTWVFLFLLSVTAGVHSEVQLVQSGGGLVKPGGSLRLSCAGSGFTFSSYSMHWLRQAPGKGLEW VSAIGTAGGTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAREYFFGSGNYGYWGQGT LVTVSSAGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAP RLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIK DG06 scFv (SEQ ID NO: 106) MEWTWVFLFLLSVTAGVHSQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGIHWVRQAPGKGLEW VAIIWHDGSNSYYVDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCARIIGGAFDIWGQGTMV TVSSAGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPEKAPKS LIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYNSYPITFGQGTRLEIK DG07 scFv (SEQ ID NO: 107) MEWTWVFLFLLSVTAGVHSEVQLVESGGGLVQPGGSLRLSCAASGFSISGYWMSWVRQAPGKGLEW VANIKQDGGEKYYGDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCVMAGGLDYWGQGTLVTV SSAGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLI YDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWYTFGQGTKLEIK In some for, the antigen binding domain of the CAR includes six CDRs. The CDRs can include at least one, two, three, four, five or six consensus CDRs of the CDRs of anti-SOD1 antibody, such as those provided herein, e.g., DG05, DG06, and DG17. The antigen binding domains also typically include heavy chain and light chain variable domains. For example, in some forms, the antigen binding domain contains at least one, two, three, four, five or six CDRs of the heavy and / or light chain variable domains, and / or the entire heavy 5245733510.1 and / or light chain variable domains of any one of SEQ ID NOS:105-107, or a variant thereof with at least 70%, 75%, 80%, 85%, 90%, or 95% sequence identity to the CDRs and / or entire heavy and light variable domains of SEQ ID NOS:105-107, optionally wherein there is 6, 5, 4, 3, 2, 1, or 0 in one, two, three, four, five, or all six of CDRs of SEQ ID NOS:105-107. Thus, in some forms, there is variation in one or more CDRs and / or the heavy chain variable domain and / or the light chain variable domain. In other embodiments the is variation in the heavy chain variable domain and / or the light chain variable domain, but not in the CDRs relative to the heavy chain variable domain and / or the light chain variable domain. (3) α-synuclein In other exemplary embodiments the CAR is one which binds to α-synuclein expressed during α-synuclein. Exemplary antigen binding components that bind to α-synuclein have the following amino acid sequences (with the font annotated to show the residues in each of leader sequence ; heavy chain framework ; heavy chain CDR1 ; heavy chain framework; heavy chain CDR2 ; heavy chain framework; heavy chain CDR3 ; heavy chain framework; linker sequence, light chain framework ; light chain CDR1 ; light chain framework ; light chain CDR2 ; light chain framework ; light chain CDR3 ; and light chain framework, respectively): DG08 scFv (SEQ ID NO: 108) MEWTWVFLFLLSVTAGVHSQVQLVQSGAEVKKPGASVRLSCRASGYNFIDFHIHWVRQAPGEGLEW MGWSNPQSGNSSSAQRFQGRVTMTTDTSMSAAYMDLNWLTLDDTAVYYCTRPHDGAGNYRFDTWGQ GTLVTVSSAGGGGSGGGGSGGGGSSYELTQPPSVSVAPGQTARITCSGDALPKHYAHWYQQKPGQV PIVVIYKDTERPSGIPERFSGSTSGTTVTLTISGVQAEDEAHYYCQSADVSSTYVVFGGGTKLTVL DG09 scFv (SEQ ID NO: 109) MEWTWVFLFLLSVTAGVHSEVQLVESGGGLVEPGGSLRLSCAVSGFDFEKAWMSWVRQAPGQGLQW VARIKSTADGGTTSYAAPVEGRFIISRDDSRNMLYLQMNSLKTEDTAVYYCTSAHWGQGTLVTVSS SERPSGVPERFSGSSSGTTATLTITGVQAEDEADYYCQSPDSTNTYEVFGGGTKLTVL 5345733510.1 DG10 scFv (SEQ ID NO: 110) MEWTWVFLFLLSVTAGVHSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYAMHWVRQAPGQRLEW MGWINAGNGKRKYSQKFQDRVTINRDTSASTIYMELSSLGSEDTAVYYCAREEDHAGSGSYLSMDV WGQGSTVTVSSAGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQNVLYSSNNKNYL AWYQQKPGHPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTITSLQTEDVAVYYCQQYYSSPLTFG GGTKVEIK DG11 scFV (SEQ ID NO: 111) MEWTWVFLFLLSVTAGVHSEVQLVETGGGLVQPKGSLKLSCATSGFTFNTYAMNWVRQAPGKGLEW VARIRTKSNDYATYYADSVKGRITISRDDSQSMLYLQMNNLKTEDTAMYYCVRVGYRPYAMDYWGQ GTSVTVSSAGGGGSGGGGSGGGGSDVLMTQTPLSLPVSLGDQASISCRSSQNIVHSNGNTYLEWYL QKPGQSPTLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPLTFGAGTK LELK In some for, the antigen binding domain of the CAR includes six CDRs. The CDRs can include at least one, two, three, four, five or six consensus CDRs of the CDRs of anti-SOD1 antibody, such as those provided herein, e.g., DG08, DG09, DG10, and DG11. The antigen binding domains also typically include heavy chain and light chain variable domains. For example, in some forms, the antigen binding domain contains at least one, two, three, four, five or six CDRs of the heavy and / or light chain variable domains, and / or the entire heavy and / or light chain variable domains of any one of SEQ ID NOS:108-111, or a variant thereof with at least 70%, 75%, 80%, 85%, 90%, or 95% sequence identity to the CDRs and / or entire heavy and light variable domains of SEQ ID NOS:108-111, optionally wherein there is 6, 5, 4, 3, 2, 1, or 0 in one, two, three, four, five, or all six of CDRs of SEQ ID NOS:108-111. Thus, in some forms, there is variation in one or more CDRs and / or the heavy chain variable domain and / or the light chain variable domain. In other embodiments the is variation in the heavy chain variable domain and / or the light chain variable domain, but not in the CDRs relative to the heavy chain variable domain and / or the light chain variable ii. Hinge Domain In some forms, the CAR includes one or more spacer domain(s) (also referred to as hinge domain) that is located between the extracellular antigen-binding domain and the transmembrane domain. A spacer domain is an amino acid segment that is generally found between two domains of a protein and may allow for flexibility of the protein and movement of one or both of the domains relative to one another. Any amino acid sequence that provides such flexibility and movement of 5445733510.1 the extracellular antigen-binding domain relative to the transmembrane domain can be used. The spacer domain can be a spacer or hinge domain of a naturally occurring protein. In some forms, the hinge domain is derived from CD8a, such as, a portion of the hinge domain of CD8a, e.g., a fragment containing at least 5 (e.g., 5, 10, 15, 20, 25, 30, 35, or 40) consecutive amino acids of the hinge domain of CD8a. Hinge domains of antibodies, such as an IgG, IgA, IgM, IgE, or IgD antibodies can also be used. In some forms, the hinge domain is the hinge domain that joins the constant CH1 and CH2 domains of an antibody. Non naturally occurring peptides may also be used as spacer domains. For example, the spacer domain can be a peptide linker, such as a (GxS)n linker, wherein x and n, independently can be an integer of 3 or more, including 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more In some embodiments, a modified Treg may include one or more CARs, and the CARs may include a hinge sequence between the AB domain and a TM domain. One of the ordinary skill in the art will appreciate that a hinge sequence is a short sequence of amino acids that facilitates flexibility (see, e.g. Woof et al., Nat. Rev. Immunol., 4(2): 89-99 (2004)). The hinge sequence can be any suitable sequence derived or obtained from any suitable molecule. In some embodiments, the length of the hinge sequence may be optimized based on the desired length of the extracellular portion of a CAR, which may be based on the location of the epitope within the target molecule. For example, if the epitope is in the membrane proximal region within the target molecule, longer hinges may be optimal. In some embodiments, the hinge may be derived from or include at least a portion of an immunoglobulin Fc region, for example, an IgG1 Fc region, an IgG2 Fc region, an IgG3 Fc region, an IgG4 Fc region, an IgE Fc region, an IgM Fc region, or an IgA Fc region. In some embodiments, the hinge includes at least a portion of an IgG1, an IgG2, an IgG3, an IgG4, an IgE, an IgM, or an IgA immunoglobulin Fc region that falls within its CH2 and CH3 domains. In some embodiments, the hinge may also include at least a portion of a corresponding immunoglobulin hinge region. In some embodiments, the hinge is derived from or includes at least a portion of a modified immunoglobulin Fc region, for example, a modified IgG1 Fc region, a modified IgG2 Fc region, a modified IgG3 Fc region, a modified IgG4 Fc region, a modified IgE Fc region, a modified IgM Fc region, or a modified IgA Fc region. The modified immunoglobulin Fc region may have one or more mutations (e.g., point mutations, insertions, deletions, duplications) resulting in one or more amino acid substitutions, modifications, or deletions that cause impaired binding of the hinge to an Fc receptor (FcR). In some aspects, the modified immunoglobulin Fc region may be designed with one or more mutations which result in one or more amino acid substitutions, modifications, or 5545733510.1 deletions that cause impaired binding of the hinge to one or more FcR including, but not limited to, FcγRI, FcγR2A, FcγR2B1, Fcγ2B2, Fcγ 3A, Fcγ 3B, FcεRI, FcεR2, FcαRI, Fcα / μR, or FcRn. In some aspects, a portion of the immunoglobulin constant region serves as a hinge between the AB domain, for example scFv or nanobody, and the TM domain. The hinge can be of a length that provides for increased responsiveness of the CAR-expressing cell following antigen binding, as compared to in the absence of the hinge. In some examples, the hinge is at or about 12 amino acids in length or is no more than 12 amino acids in length. Exemplary hinges include those having at least about 10 to 229 amino acids, about 10 to 200 amino acids, about 10 to 175 amino acids, about 10 to 150 amino acids, about 10 to 125 amino acids, about 10 to 100 amino acids, about 10 to 75 amino acids, about 10 to 50 amino acids, about 10 to 40 amino acids, about 10 to 30 amino acids, about 10 to 20 amino acids, or about 10 to 15 amino acids, and including any integer between the endpoints of any of the listed ranges. In some embodiments, a hinge has about 12 amino acids or less, about 119 amino acids or less, or about 229 amino acids or less. Exemplary hinges include a CD28 hinge, IgG4 hinge alone, IgG4 hinge linked to CH2 and CH3 domains, or IgG4 hinge linked to the CH3 domain. Exemplary hinges include, but are not limited to, those described in Hudecek et al. (2013) Clin. Cancer Res., 19:3153, international patent application publication number WO2014031687, U.S. Pat. No.8,822,647 or published App. No. US2014 / 0271635. In some embodiments, the hinge sequence is derived from CD8α molecule, a DAP10 molecule, a CD8a molecule, or a CD28 molecule. In a preferred embodiment, the hinge sequence is derived from CD28. In one embodiment, the hinge includes the amino acid sequence of human CD28 hinge or the hinge has an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In some embodiments, the hinge includes the amino acid sequence of mouse CD28 hinge or has an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In one embodiment, the hinge includes the amino acid sequence of human CD8A hinge or the hinge has an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In one embodiment, the hinge includes the amino acid sequence of human DAP10 hinge or the hinge has an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. Non-limiting examples of hinge domains that can be used in the disclosed constructs include the following, and others provided in the sequence appendix and sequence list. 5645733510.1 HUMAN CD28 HINGE (SEQ ID NO: 132) VKGKHLCPSPLFPGPSKP MOUSE CD28 HINGE (SEQ ID NO: 133) IKEKHLCHTQSSPKL HUMAN CD8A HINGE (SEQ ID NO: 134) TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD HUMAN DAP10 HINGE (SEQ ID NO: 135) QTTPGERSSLPAFYPGTSGSCSGCGSLSLP iii. Transmembrane (TM) domain In some forms, the CAR includes a transmembrane domain that can be directly or indirectly fused to the antigen-binding domain. The transmembrane domain may be derived either from a natural or a synthetic source. In some forms, the transmembrane domain of the CAR includes a transmembrane domain of an alpha, beta or zeta chain of a T cell receptor, CD8, CD4, CD28, CD137, CD80, CD86, CD152 (CTLA-4) or PD1, or a portion thereof. Transmembrane domains can also contain at least a portion of a synthetic, non-naturally occurring protein segment. In some forms, the transmembrane domain is a synthetic, non-naturally occurring alpha helix or beta sheet. In some forms, the protein segment is at least about 15 amino acids, e.g., at least 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more amino acids. Examples of synthetic transmembrane domains are known in the art, for example in U.S. Patent No.7,052,906 and PCT Publication No. WO 2000 / 032776In some embodiments, a modified Treg may include one or more CARs, and the CARs may include a TM domain. With respect to the TM domain, a CAR can be designed to include a TM domain that is fused to the AB domain of the CAR. A hinge sequence may be inserted between the AB domain and the TM domain. In some embodiments, a TM domain that naturally is associated with one of the domains in the CAR is used. In some instances, the TM domain can be selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins to minimize interactions with other members of the receptor complex. A TM domain may be derived either from a natural or from a synthetic source. Where the source is natural, the domain may be derived from any membrane-bound or transmembrane protein. Typically, the TM domain denotes a single transmembrane α helix of a transmembrane protein, also known as an integral protein. TM domains of particular use in this disclosure may be derived from (i.e. include at least the transmembrane region(s) of) CD28, CD3 ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA- 5745733510.1 4, TCR α, TCR β, or CD3 zeta and / or TM domains containing functional variants thereof such as those retaining a substantial portion of the structural, e.g., transmembrane, properties thereof. Alternatively, the TM domain may be synthetic, in which case the TM domain will include predominantly hydrophobic residues such as leucine and valine. Preferably a triplet of phenylalanine, tryptophan and valine will be found at each end of a synthetic TM domain. A TM domain of the disclosure is thermodynamically stable in a membrane. It may be a single α helix, a transmembrane β barrel, a β-helix of gramicidin A, or any other structure. Transmembrane helices are usually about 20 amino acids in length. In some preferred embodiments, the TM domain in a CAR may be derived from the TM region of CD28. In one embodiment, the TM domain includes the amino acid sequence of human CD28 TM or the TM domain includes an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In one embodiment, the TM domain includes the amino acid sequence of mouse CD28 TM or the TM domain includes an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In one embodiment, the TM domain includes the amino acid sequence of human CD8A TM or includes an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. In one embodiment, the TM domain includes the amino acid sequence of human DAP10 TM or the TM domain includes an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. Optionally, a short oligo- or polypeptide spacer, preferably between 2 and 10 amino acids in length may form the linkage between the TM domain and the ICS domain(s) of a CAR. A glycine-serine doublet may provide a suitable spacer. Non-limiting examples of TM domains that can be used in the disclosed constructs include the following, and others provided in the sequence appendix and sequence list. HUMAN CD28 TM (SEQ ID NO: 136) FWVLVVVGGVLACYSLLVTVAFIIFWV MOUSE CD28 TM (SEQ ID NO: 137) FWALVVVAGVLFCYGLLVTVALCVIWT HUMAN CD8A TM (SEQ ID NO: 138) IYIWAPLAGTCGVLLLSLVITLYC HUMAN DAP10 TM (SEQ ID NO: 139) LLAGLVAADAVASLLIVGAVF 5845733510.1 iv. Intracellular Signaling or Co-Stimulatory Domains The intracellular signaling domain is responsible for activation of at least one of the normal effector functions of the immune effector cell expressing the CAR. The term effector function refers to a specialized function of a cell. Effector function of a T cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines. In some forms, an intracellular signaling domain includes the zeta chain of the T cell receptor or any of its homologs (e.g., eta, delta, gamma or epsilon), MBl chain, B29, Fc RIII, Fc RI and combinations of signaling molecules such as CD3ζ and CD28, 41BB, OX40 and combination thereof, as well as other similar molecules and fragments. Intracellular signaling portions of other members of the families of activating proteins can be used, such as FcγRIII and FcεRI. Many immune effector cells require co stimulation, in addition to stimulation of an antigen- specific signal, to promote cell proliferation, differentiation and survival, as well as to activate effector functions of the cell. Therefore, in some forms, the CAR includes at least one co- stimulatory signaling domain. The term co stimulatory signaling domain, refers to at least a portion of a protein that mediates signal transduction within a cell to induce an immune response such as an effector function. The co stimulatory signaling domain can be a cytoplasmic signaling domain from a co stimulatory protein, which transduces a signal and modulates responses mediated by immune cells, such as T cells, NK cells, macrophages, neutrophils, or eosinophils. In some forms, the co- stimulatory signaling domain is derived from a co-stimulatory molecule selected from CD27, CD28, CD137, 0X40, CD30, CD40, CD3, LFA 1, ICOS, CD2, CD7, LIGHT, NKG2C, B7 H3, ligands of CD83 and combinations thereof. In other exemplary embodiments, modified Tregs may include one or more CARs and may further include one or more signaling domains which may be encoded by nucleic acids which are included on the same or different nucleic acid construct as the nucleic acids encoding the one or more CARs. The signaling domains may activate different effector pathways and / or survival pathways in the modified Tregs and optionally may affect cytokine expression, e.g., trigger IL-10 expression in the presence of a target antigen such as a protein highly expressed in the CNS at a site of neurodegeneration. In some exemplary embodiments, modified Tregs may have no signaling, or T cell signaling may be used (i.e. an antigen tether as CAR, e.g., CD28 transmembrane only). In other exemplary embodiments, one or more CARs expressed by the modified Tregs may include signaling domain combinations (co-stimulation signaling domains) including by way of example: CD28-CD3ζ; 4-1BB-CD3ζ; Dap10-CD3ζ; CD44-CD3ζ; CTLA-4-CD3ζ; CD28; Dap10; 4-1BB; CD3-ζ. In further exemplary embodiments, a co-stimulation signaling domain expressed by the 5945733510.1 modified Tregs may include CD28-CD3ζ; DAP10-CD3ζ; CD44-CD3ζ; 4-1BB-CD3ζ; CD28; or CD3-ζ. In some embodiments, a modified Treg may include one or more CARs, and the CARs may include a ICS and / or CS domain. The ICS domain or otherwise the cytoplasmic domain of a CAR may trigger or elicit activation of at least one of the normal functions of the cell in which the CAR has been placed, for example, the secretion of cytokines. Thus, the term "intracellular signaling domain" or “ICS domain” refers to the portion of a protein which transduces a functional signal and directs the cell to perform a specialized function. While usually the entire ICS domain may be employed, in many cases it is not necessary to use the entire chain. To the extent that a truncated portion of the intracellular signaling domain is used, such truncated portion may be used in place of the intact chain as long as it transduces the function signal. The term "intracellular signaling domain" or “ICS domain” is thus meant to include any truncated portion of the ICS domain sufficient to transduce a function signal. Signals generated through one ICS domain alone may be insufficient for full activation of a cell, and a secondary or costimulatory signal may also be required. In such cases, a costimulatory domain (CS domain) may be included in the cytoplasmic portion of a CAR. A CS domain is a domain that transduces such a secondary or costimulatory signal. Optionally, a CAR may include two or more CS domains. The CS domain(s) may be placed upstream of the ICS domain or downstream of the ICS domain. For example, T cell activation can be the to be mediated by two distinct classes of cytoplasmic signaling sequence: those that initiate antigen-dependent primary activation through the T cell receptor (TCR) (primary cytoplasmic signaling sequences) and those that act in an antigen-independent manner to provide a secondary or costimulatory signal (secondary cytoplasmic signaling sequences). Primary cytoplasmic signaling sequences regulate primary activation of the TCR complex either in a stimulatory way, or in an inhibitory way. Primary cytoplasmic signaling sequences that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine-based activation motifs or ITAMs. Such a cytoplasmic signaling sequence may be contained in the ICS or the CS domain of a CAR. Examples of ITAM-containing primary cytoplasmic signaling sequences that are of particular use may include those derived from an ICS domain of a lymphocyte receptor chain, a TCR / CD3 complex protein, an Fc receptor subunit, an IL-2 receptor subunit, CD3 ζ, FcR γ, FcR β, CD3 γ, CD3 δ, CD3 ε, CD5, CD22, CD66d, CD79a, CD79b, CD278 (ICOS), Fc ε RI, DAP10, and DAP12. 6045733510.1 In some embodiments, an ICS domain in a CAR may include a cytoplasmic signaling sequence derived from CD3 zeta or the ICS domain includes an amino acid sequence at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical thereto. Various CS domains have been reported to confer differing properties (Gacerez et al. J. Cell. Physiol.231: 2590–2598, 2016). For example, the 4-1BB CS domain has been reported to exhibit enhanced persistence in some in vivo xenograft models (Milone et al. Mol Ther 2009;17:1453-1464; Song et al. Cancer Res 2011;71:4617-4627). Additionally, these different CS domains produce different cytokine profiles, which in turn, may produce different effects on target cell-mediated cytotoxicity and the disease microenvironment. Examples of co-stimulatory molecules include MHC class I molecules, TNF receptor proteins, immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocytic activation molecules (SLAM proteins), activating NK cell receptors, a Toll ligand receptor, B7-H3, BAFFR, BTLA, BLAME (SLAMF8), CD2, CD4, CD5, CD7, CD8 α, CD8 β, CD11a, LFA-1 (CD11a / CD18), CD11b, CD11c, CD11d, CD18, CD19, CD19a, CD27, CD28, CD29, CD30, CD40, CD44, CD49a, CD49D, CD49f, CD69, CD84, CD96 (Tactile), CD100 (SEMA4D), CD103, CRTAM, OX40 (CD134), 4-1BB (CD137), SLAM (SLAMF1, CD150, IPO-3), CD160 (BY55), SELPLG (CD162), DNAM1 (CD226), Ly9 (CD229), SLAMF4 (CD244, 2B4), ICOS (CD278), CEACAM1, CDS, CRTAM, DAP10, GADS, GITR, HVEM (LIGHTR), IA4, ICAM-1, IL2R β, IL2R γ, IL7R α, ITGA4, ITGA6, ITGAD, ITGAE, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, ITGB7, KIRDS2, LAT, LFA-1, LIGHT, LTBR, NKG2C, NKG2D, NKp30, NKp44, NKp46, NKp80 (KLRF1), PAG / Cbp, PD-1, PSGL1, SLAMF6 (NTB-A, Ly108), SLAMF7, SLP-76, TNFR2, TRANCE / RANKL, VLA1, VLA-6, a ligand that specifically binds with CD83, and the like. The ICS domain and the CS domain(s) of a CAR may be linked to each other in a random or specified order. Optionally, a short oligo- or polypeptide linker, preferably between 2 and 10 amino acids in length may form the linkage. A glycine-serine doublet provides a particularly suitable linker. Non-limiting examples of costimulatory domains that can be used in the disclosed constructs include the following, and others provided in the sequence appendix and sequence list. 4-1BB CO-STIMULATORY DOMAIN (SEQ ID NO: 112) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL CD3Z (SEQ ID NO: 116) RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 45733510.1 2. IL-2 and IL-2 Mutein Sequences The constructs and Tregs can also include an IL-2, an IL-2 mutein, STAT5B, or STAT5A. Exemplary sequences are provided and include, WT human IL-2 AMINO ACID SEQUENCE (SEQ ID NO: 25) MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYM PKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSIISTLT Muteins WE3 AMINO ACID SEQUENCE (SEQ ID NO: 27) MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINSYKNPKLTRMLTFKFYM PKKATELKHLQCLEEELKPLEEALNLAPSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSTISTLT WC9 AMINO ACID SEQUENCE (SEQ ID NO: 29) MYRMQLLSCIALSLALVTNSAPTPSSTKKARLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYM PKKATELKHLQCLEEELKPLEEALNLAPSKNFHLRPRDLISDINVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSIISTLA M6 AMINO ACID SEQUENCE (SEQ ID NO: 31) MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYM PKKATELKHLQCLEEELKPLEEALNLAPSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSTISTLT 1b8 AMINO ACID SEQUENCE (SEQ ID NO: 33) MYRMQLLSCIALSLALVTNSAPTSSSTRKTQLRLEHLLLDLQMILDGINTYKNPRLRRMLTFKFYM PKKATELKHLQCLEEELKPLEEALNLAPSKNFHLRPRDLISNINVTVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSIISTLT 1a-1 AMINO ACID SEQUENCE (SEQ ID NO: 35) MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGINSYKNPKLTRMLTFKFYM PKKATELKHLQCLEEELKPLEDALALAPPRNFHLRPRDLISNIHVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSIISTLT 2-4 AMINO ACID SEQUENCE (SEQ ID NO: 37) MYRMQLLSCIALSLALVTNSAPTSSSTKKTQLQLEHLLLDLQMILNGISNHKNPRLARMLTFKFYM PEKATELKHLQCLEEELKPLEEALRLAPSKNFHLRPRDLISDVNVIVLELKGSETTFMCEYADETA TIVEFLNRWITFCQSIISTLT 6245733510.1 each with and without the signal sequence (illustrated in the first sequence with italics), and variants of the foregoing with at least 70%, 75%, 80%, 85%, 90%, 95% sequence identity thereto. B. Exemplary Constructs Specific exemplary embodiments of the present disclosure relate to modified Tregs that include one or CARs which include single chain variable fragments that were derived from antibodies specific to proteins and / or other molecular markers associated with diseases and / or conditions associated with diseases, such as, for example, neurodegenerative diseases and / or neuroinflammation including but not limited to specific scFv antibody sequences which are disclosed herein. Typically, when a polycistronic nucleic acid construct includes nucleic acid sequences encoding a CAR; and encoding either IL2, and / or an IL2 mutein, and / or constitutively active STAT5B (STAT5B-CA), and / or constitutively active STAT5A (STAT5A-CA); and DMM coding sequences, optionally BDNF or IGF-1 are oriented from 5’ to 3’ orientation in the CAR construct as follows: [CAR] - [IL2 / IL2 / STAT5B-CA / STAT5A-CA] - [DMM]; or [DMM] - [IL2 / IL2 / STAT5B-CA / STAT5A-CA] - [CAR]. Typically, the IL2 / IL2 / STAT5B-CA / STAT5A-CA is flanked by at least one coding region for a DMM or a CAR. In some embodiments, a modified Treg may include DG05-28Z, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include CAR DG06-28Z, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include CAR DG07-28Z, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include CAR DG10-28Z, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG01-CD28-CD3ζ, DG02-CD28-CD3ζ, DG04-CD28-CD3ζ, DG15-CD28-CD3ζ DG164-CD28-CD3ζ, or a sequence including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs. In some embodiments, a modified Treg may include DG05-CD28-CD3ζ, DG06-CD28-CD3ζ, DG07-CD28-CD3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs. In some embodiments, a modified Treg may include 6345733510.1 DG08-CD28-CD3ζ, DG09-CD28-CD3ζ, DG10-CD28-CD3ζ, DG11-CD28-CD3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs. In some embodiments, a modified Treg may include DG05-CD28-CD3ζ (also referred to as DG05-28-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28tm-DAP10-CD3ζ (also referred to as DG05-28tm-10-3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28tm-CD44-CD3ζ (also referred to as DG05-28tm-44-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28tm- CD3ζ (also referred to as DG05-28tm-3ζ) and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28 (also referred to as DG05-28) and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28tm (also referred to as DG05-28tm) and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG03-CD28-CD3ζ (also referred to as DG03-28-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG03-CD28tm- DAP10-CD3ζ (also referred to as DG03-28tm-10-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG15-CD28tm-DAP10-CD3ζ (also referred to as DG15-28tm-10-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG16-CD28tm-DAP10-CD3ζ (also referred to as DG16-28tm-10-3ζ), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG03-CD28tm- CD44-CD3ζ (also referred to as DG03-28tm-44-3ζ) and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG03-CD28tm-4-1-BB-CD3ζ (also referred to as DG03-28tm-BB-3ζ), DG15-CD28tm-4-1-BB-CD3ζ, DG16-CD28tm-4-1-BB-CD3ζ and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the 6445733510.1 aforementioned constructs. In some embodiments, a modified Treg may include DG03-CD28tm- CD3ζ (also referred to as DG03-28tm-3ζ), DG15-CD28tm-CD3ζ, DG16-CD28tm-CD3ζ and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned constructs. In some embodiments, a modified Treg may include DG03-CD28 (also referred to as DG03-28), DG15-CD28, DG16-CD28 (and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned constructs. In some embodiments, a modified Treg may include DG03-CD28tm (also referred to as DG03-28tm), DG15-CD28tm, DG16-CD28tm and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned constructs. In further exemplary embodiments, modified Tregs according to the disclosure may express one or more CARs, e.g., which target proteins aberrantly expressed at a site of CNS neurodegeneration and may further be modified to express one or more NDMMs. Alternatively modified Tregs may be generated which express one or more NDMMs which do not express a CAR. These modified NDMM expressing Tregs optionally may be combined with modified Tregs which express one or more CARs. The NDMMs may include molecules that prevent oxidative and / or inflammatory activity. In further exemplary embodiments, the NDMMs when expressed in Tregs may activate neuronal growth and / or survival. Exemplary NDMMs may include pro-neuronal factors, anti-oxidants, nerve growth factors, and / or non-classical neurotrophic factors. Exemplary anti-oxidants include, but are not limited to including, HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin. Exemplary pro-neuronal factors include, but are not limited to including: interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs). Exemplary nerve growth factors include, but are not limited to including, classic neurotrophins: Brain-derived neurotrophic factor (BDNF), Ciliary neurotrophic factor (CNTF), Glial cell-line derived neurotrophic factor (GDNF). Exemplary non-classical neurotrophic factors include, but are not limited to including, Insulin-like growth factor-1 (IGF-1), Vascular endothelial growth factor, VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), Granulocyte- colony stimulating factor (G-CSF). In some exemplary embodiments, NDMMs which are expressed by modified Tregs according to the disclosure may be controlled by a constitutive promoter. In other exemplary embodiments, NDMMs which are expressed by modified Tregs according to the 6545733510.1 disclosure may be controlled by an inducible promoter system. The selection of suitable constitutive and inducible promoters is well within the skill in the art and many such promoters are known and readily available. Furthermore, expression of the NDMMs by the modified Tregs may be regulated by CAR-triggered transcriptional control. In some embodiments of the present disclosure, CAR- expressing modified Tregs as described herein may further include exogenously introduced polynucleotides encoding one or more NDMMs. In some embodiments, the exogenously introduced polynucleotides encoding an NDMM and the CAR construct may be introduced into the cell using a single vector. When one vector is used for both a CAR and an NDMM, the CAR and the NDMM may be encoded in the vector under the same promoter in cis. In such cases, the CAR and NDMM constructs may be separated by a sequence that allows generation of two separate translation products, for example an IRES sequence or T2A sequence. In some embodiments, a CAR-expressing modified Treg may express an NDMM which may be human catalase. In some embodiments, a CAR-expressing modified Treg may express an NDMM which may be Neh2 domain of human Nrf2. In some embodiments, a CAR-expressing modified Treg may express an NDMM which may be human BDNF. In some embodiments, a CAR-expressing modified Treg may express an NDMM which may be human IGF-1. In some embodiments, a modified Treg may include a construct for expression of the NDMM Nrf2 (Keap1 inhibitor peptide), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include a construct for expression of the NDMM human catalase, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include a construct for expression of the NDMM BDNF, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include a construct for expression of the NDMM IGF-1, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. Alternatively, a CAR construct and NDMM construct may be contained in separate vectors for transfecting or transducing cells using two or more different vectors. Exemplary modified Tregs may include modified Tregs targeting proteins and / or molecular markers of Parkinson’s disease. In exemplary embodiments, modified Tregs targeted to Parkinson’s disease may include one or more CARs, wherein the one or more CARs may target α-synuclein fibrils. In some embodiments, a CAR targeted to alpha-synuclein may include a sequence of DG08, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to alpha-synuclein 6645733510.1 may include a sequence of DG09, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to alpha-synuclein may include a sequence of DG10, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to alpha-synuclein may include a sequence of DG11, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG08-CD28-CD3ζ, DG09-CD28-CD3ζ, DG10-CD28-CD3ζ, DG11-CD28-CD3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs, wherein each of the constructs is targeted to alpha- synuclein. In further exemplary embodiments, modified Tregs, such as modified Tregs including one or more CARs, may target one or more neurotoxic inflammatory mediators, e.g., neurotoxic inflammatory mediations produced by activated microglia. The modified Tregs may decrease and / or inhibit microglia activation. In exemplary embodiments, modified Tregs include targeted anti-inflammatory and neuroprotective therapeutic activity at the disease site of dopamine neuron degeneration in PD. In some embodiments, modified Tregs may mediate their function only at the site where α-synuclein fibrils are present. In exemplary embodiments, modified Tregs may include one or more CARs and / or one or more NDMMs targeted to Parkinson’s disease, wherein the one or more CARs include single chain variable fragments such as VHand VLamino acid sequences of human and mouse monoclonal antibodies against human α-synuclein fibrils (such as, for example, amino acid sequences derived from clones NI 202.3G12, NI 202.12F4, NI 202.21D11, and mAb49 / G). In exemplary embodiments, modified Tregs may include the scFV and further include a construct including CD28-CD3ζ CAR, i.e., scFv-CD28-CD3ζ CAR, wherein the scFv is specific for human α-synuclein fibrils. Constructs including the scFv may include VH+VLand VL+VHarrangements. In exemplary embodiments, a vector may include the scFv-CD28-CD3ζ CAR construct and may further include a separate truncated (non-signaling) human CD19 (tCD19). The tCD19 may be used as a transduction marker, such as for cell monitoring and / or cell purification purposes. In exemplary embodiments, a vector including any of the sequences described herein may include a retroviral expression vector, e.g., pSFG. Furthermore, in exemplary embodiments, modified Tregs may include one or more CARs and / or one or more NDMMs targeted to ALS. The modified Tregs may target huSOD1, e.g., the modified Tregs may include one or more CARs targeted to HuSOD1. In some embodiments, a CAR targeted to huSOD1 may include a sequence of DG05, and / or a construct including at least 6745733510.1 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to HuSOD1 may include a sequence of DG06, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to huSOD1 may include a sequence of DG07, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG05-CD28-CD3ζ, DG06-CD28-CD3ζ, DG07-CD28-CD3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs, wherein each of the constructs is targeted to HuSOD1. In some embodiments, a modified Treg may include DG05-CD28-CD3ζ (also referred to as DG05-28- 3ζ); DG05-CD28tm-DAP10-CD3ζ (also referred to as DG05-28tm-10-3ζ); DG05-CD28tm-CD44- CD3ζ (also referred to as DG05-28tm-44-3ζ); DG05-CD28tm-CD3ζ (also referred to as DG05- 28tm-3ζ); DG05-CD28 (also referred to as DG05-28); DG05-CD28tm (also referred to as DG05- 28tm), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs, wherein each of the constructs is targeted to huSOD1. In some embodiments, modified Tregs may include CARs targeted to HuSOD1, and in some exemplary embodiments an scFv of the CARs may be expressed extracellularly with the C- terminus of the VL fused to human CD28 hinge, transmembrane, and cytoplasmic domain, followed by a human CD3ζ cytoplasmic domain to create an anti-huSOD1-CD28-CD3ζ CAR. In some embodiments, an scFv of a CAR included by a modified Treg may be constructed by linking heavy chain variable region and light chain variable region with a linker, such as, for example, a (G4S)3 (SEQ ID NO: 113) linker. In some embodiments, the C-terminus of a VLof a CAR of a modified Treg may be fused with human CD28 hinge, transmembrane, and cytoplasmic domain, and may be followed by a human CD3ζ cytoplasmic domain. The CAR of the modified Treg may be an anti- HuSOD1 CAR. The CARs may trigger both primary and costimulation signaling upon antigen binding, e.g., binding of huSOD1. In some embodiments, a CAR costimulatory domain may include, but not limited to one including, CD3ζ alone, 4-1BB, or CD28 or it may include CD28- CD3ζ, DAP10-CD3ζ or CD44-CD3ζ. In some embodiments a truncated (non-signaling) human CD19 (tCD19) may also expressed in the same vector as the CARS, such as by using a 2A co- expression system, the tCD19 may serve as a way to track and purify transduced T cells. In some embodiments, modified Tregs targeted to ALS may enter the spinal cord when administered to a patient in need of treatment. In exemplary embodiments, modified Tregs may include markers such as, for example, VLA4, LFA-1, CCR6, or CXCR3. In some exemplary embodiments, modified 6845733510.1 CARs targeted to ALS, e.g., modified Tregs including one or more anti-huSOD1 CARs, and optionally will retain a Treg phenotype and / or elicit at least some Treg effector functions when expressing one or more CARs and / or one or more NDMMs. In exemplary embodiments, modified Tregs may express IL-10 in response to an ALS protein and / or molecular marker of disease. In some exemplary embodiments, modified Tregs according to the disclosure may secrete anti-inflammatory cytokines, which may result in inhibition of activated microglia and / or macrophages. The secretion may occur as a result of stimulation of one or more CARs included by the modified Tregs by an ALS protein and / or disease associated marker, such as huSOD1. In some embodiments, the cytokines may include IL-10, IL-4, or TGF-β. In some exemplary embodiments, modified Tregs may reduce and / or prevent production of neurotoxic free radicals and inflammatory cytokines by microglia. In some exemplary embodiments, modified Tregs may be used in methods of treating ALS, and the methods may result in one or more of the following as compared to a control treatment: less macrophage mediated motor neuron death; less IL-1β, TNF-α, nitric oxide and / or free radicals (superoxide anion); and greater amounts of IL-10, IL-4, and TGF-β. In some exemplary embodiments, modified Tregs may include CARs targeted to the short isoform of C9orf72 (sC9orf72), which, like huSOD1, may be expressed on or near motor neurons in subjects with ALS. In some exemplary embodiments, modified Tregs may include CARs that target TDP43, which is expressed on or near motor neurons in subjects with both familial and sporadic forms of ALS. In exemplary embodiments, modified Tregs may include CARs targeted to sC9orf72, wherein the CAR may include a human scFV against sC9orf72. In some specific exemplary embodiments, CARs targeted to sC9orf27 may include anti-sC9orf72 CARs using VHand VLsequences from a unique human αsC9orf72. In some embodiments, the VL c-terminus of each αsC9orf72 scFv may be fused with human CD28 hinge, transmembrane, and cytoplasmic domain, followed by a human CD3ζ cytoplasmic domain to create an anti-sC9orf72 CAR that may be included by a modified Treg. In some embodiments, a non- signaling, truncated human CD19 (tCD19) can serve as a transduction marker on a vector including the CARs. In exemplary embodiments, modified Tregs targeted to sC9orf72 may inhibit microglia mediated motor neuron degeneration; decrease IL-1β, TNF-α, nitric oxide; and / or increase IL-10. IL-4, and TGF-β, such as when administered to a patient in need of treatment. In some exemplary embodiments, modified Tregs may include modified Tregs targeted to ALS, such as modified Tregs including anti-huSOD1 CARs, and the modified Tregs may enter the spinal cord parenchyma, recognize accumulated spinal huSOD1 protein, and react by producing 6945733510.1 anti-inflammatory mediators. The modified Tregs may decrease expression of inflammatory mediators (e.g. CCL2, CCL3, CCL4, TNF-α, IL1β, NOX2) and increase expression of anti- inflammatory mediators (e.g. IL-10, IL-4, and TGF-β) when administered to a patient in need of treatment. Furthermore, modified Tregs targeted to ALS, such as modified Tregs including anti- huSOD1 CARs, may inhibit persistent and / or neurotoxic inflammation around motor neurons when used in methods of treatment of ALS. Furthermore, in other exemplary embodiments, modified Tregs may be targeted to proteins and / or molecular markers associated with Alzheimer’s disease. In some exemplary embodiments, the modified Tregs may include one or more CARs targeted to the proteins and / or markers. In some embodiments, the protein and / or marker may include amyloid-beta (Aβ), in particular oligomeric Aβ, and / or intraneuronal tangles of twisted tau protein fibers. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG01, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG02, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG03, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG04, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the aforementioned construct. In some embodiments, a modified Treg may include DG01-CD28-CD3ζ, DG02-CD28-CD3ζ, DG03-CD28- CD3ζ, DG04-CD28-CD3ζ, and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs, wherein each of the constructs is targeted to amyloid-beta. In some embodiments, a modified Treg may include DG03-CD28-CD3ζ (also referred to as DG03-28-3ζ); DG03-CD28tm-DAP10-CD3ζ (also referred to as DG03-28tm-10-3ζ); DG03-CD28tm-CD44-CD3ζ (also referred to as DG03-28tm-44-3ζ); DG03-CD28tm-4-1-BB-CD3ζ (also referred to as DG03-28tm-BB-3ζ); DG03-CD28tm-CD3ζ (also referred to as DG03-28tm-3ζ); DG03-CD28 (also referred to as DG03-28); and / or DG03-CD28tm (also referred to as DG03-28tm), and / or a construct including at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to any one or more of the aforementioned constructs, wherein each of the constructs is targeted to amyloid-beta. In exemplary embodiments, CARs included by modified Tregs may be targeted to Aβ peptides and may include anti-Aβ CARs using single chain variable fragment (scFv) sequences from antibodies, e.g., human and / or humanized antibodies, with different binding specificities to 7045733510.1 Aβ, e.g., oligomeric Aβ. In exemplary embodiments, the scFvs may be fused to human CD28 hinge, transmembrane, and cytoplasmic domains, followed by a human CD3ζ cytoplasmic domain. The CARs may trigger both primary (CD3ζ) and co-stimulatory (CD28) signaling upon antigen binding and cross-linking. In some embodiments, a truncated (non-signaling) CD19 (tCD19) may also expressed in the same vector including the CARs, such as by using a T2A co-expression system, and it may serve as a means to track and purify transduced T cells. Modified Tregs including anti- Aβ CARs may suppress proliferation of CD3-activated allogeneic CD8+T cells in some embodiments. Furthermore, in some embodiments, when activated with oligomeric Aβ, modified Tregs including anti-Aβ CARs may produce anti-inflammatory cytokines, e.g., IL-10. Furthermore, the modified Tregs may inhibit production of pro-inflammatory mediators and may enhance phagocytic capacity of activated microglia or macrophages, such as by secreting IL-10, TGF-β, and IL-4 anti-inflammatory cytokines for example. In some exemplary embodiments, modified Tregs according to the disclosure which express a CAR specific for oligomeric Aβ may have targeted anti-inflammatory activity and neuroprotective effects in regions where oligomeric Aβ may accumulate. In some exemplary embodiments, e.g., modified Tregs which express a CAR specific for oligomeric Aβ may migrate to the hippocampus, wherein oligomeric Aβ may accumulate. Moreover, in some exemplary embodiments, modified Tregs including anti-Aβ CARs may traffic and accumulate to brain regions of Aβ deposits and neuroinflammation, wherein such regions may include sites of Aβ deposits in the hippocampus and frontal cortex. In some embodiments, modified Tregs including CARs targeting Alzheimer’s may accumulate in the brain regions and may lead to increased expression of human anti-inflammatory cytokines IL-10, TGF-β, and IL4 in the regions. These anti-inflammatory cytokines may lead to decreased expression of pro- inflammatory mediators and the numbers of activated microglia. In some exemplary embodiments, modified Tregs including CARs targeting Alzheimer’s disease may improve memory function in a patient treated with the modified Tregs. Specific features of and / or that may be included by modified Tregs and / or specific features that may be included by targets of modified Tregs are discussed in greater detail below and further examples are illustrated in the sequence listing. C. Further modifications In some embodiments, a modified Treg may include one or more CARs, and the CARs may include further modifications. In some embodiments, one or more CARs, nucleotide sequences encoding the same, vectors encoding the same, and cells including nucleotide sequences encoding the CARs may be further modified, engineered, optimized, or appended in order to provide or select for various features. These features may include, but are not limited to, efficacy, persistence, target 7145733510.1 specificity, reduced immunogenicity, multi-targeting, enhanced immune response, expansion, growth, reduced off-target effects, reduced subject toxicity, detection, selection, targeting, and the like. For example, the cells may be engineered to express another CAR, or to have a suicide mechanism, and may be modified to remove or modify expression of an endogenous receptor or molecule such as a TCR and / or MHC molecule. In some embodiments, a vector or nucleic acid sequence encoding a CAR further encodes other genes. The vector or nucleic acid sequence may be constructed to allow for the co-expression of multiple genes using a multitude of techniques including co-transfection of two or more plasmids, the use of multiple or bidirectional promoters, or the creation of bicistronic or multicistronic vectors. The construction of multicistronic vectors may include the encoding of IRES elements or 2A peptides, such as T2A, P2A, E2A, or F2A (for example, see Kim, J.H., et al., “High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice”, PLoS One.2011;6(4)). In some embodiments, the nucleic acid sequence or vector encoding a CAR further encodes tCD19 with the use of a T2A ribosomal skip sequence. CARs included by modified Tregs according to the disclosure optionally may be further modified to improve efficacy against cells expressing the target molecule. In some embodiments, the improved efficacy may be measured by a decrease in microglial cell activation, a decrease in inflammatory response, and / or a decrease in neuronal death. In some embodiments, modified Tregs including one or more CARs may further include more than a CAR. Additional CARs may or may not be specific for the target molecule of the first CAR. In some embodiments, the one or more additional CARs may act as inhibitory or activating CARs. In some aspects, a CAR of some embodiments is the stimulatory or activating CAR; in other aspects, it is the costimulatory CAR. In some embodiments, modified Tregs may further include inhibitory CARs (iCARs, see Fedorov et al., Sci. Transl. Medicine, 2013 Dec;5(215): 215ra172), such as a CAR recognizing an antigen other than the target molecule of the first CAR, whereby an activating signal delivered through the first CAR is modified or altered by binding of the inhibitory CAR to its ligand, e.g., to reduce off-target effects. D. Vectors or Constructs The present disclosure also provides vectors or constructs such as plasmids or retroviral constructs in which a DNA may be inserted such as one encoding a CAR. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine 7245733510.1 leukemia viruses in that they can transduce non-proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. In brief summary, the expression of natural or synthetic nucleic acids encoding CARs may typically achieved by operably linking a nucleic acid encoding a CAR polypeptide or portions thereof to a promoter, and incorporating the construct into an expression vector. The vectors can be suitable for replication and integration eukaryotes. Typical cloning vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the desired nucleic acid sequence. The expression constructs of the present disclosure may also be used for nucleic acid immunization and gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art. See, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties. The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. Further, the expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al. (2001, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, γ-retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Pat. No.6,326,193). A number of viral based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo. A number of retroviral systems are known in the art. In some embodiments, adenovirus vectors are used. A number of adenovirus vectors are known in the art. In one embodiment, lentivirus vectors are used. Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functional elements downstream of the 7345733510.1 start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. Depending on the promoter, it appears that individual elements can function either cooperatively or independently to activate transcription. Various promoter sequences may be used, including, but not limited to the immediate early cytomegalovirus (CMV) promoter, the CMV-actin-globin hybrid (CAG) promotor, Elongation Growth Factor-1α (EF-1α), simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the hemoglobin promoter, and the creatine kinase promoter. Inducible promoters are also contemplated for use. The use of an inducible promoter provides a molecular switch capable of turning on expression of the polynucleotide sequence which it is operatively linked when such expression is desired, or turning off the expression when expression is not desired. Examples of inducible promoters include, but are not limited to a metallothionein promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline promoter. In order to assess the expression of a CAR polypeptide or portions thereof, the expression vector to be introduced into a cell can also contain either a selectable marker gene or a reporter gene or both to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors. In other aspects, the selectable marker may be carried on a separate piece of DNA and used in a co-transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as neo and the like. In some embodiments, the selectable marker gene includes a nucleic acid sequence encoding truncated CD19 (trCD19). Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include genes encoding luciferase, β-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei 7445733510.1 et al., 2000 FEBS Letters 479: 79-82). Suitable expression systems are well known and may be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5' flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription. E. Transduction of Tregs Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. In some forms, the modified Tregs are transduced and / or stimulated for optimal Treg cell expansion, viability, CAR expression, and to maintain the Treg phenotype. In exemplary forms, cells are stimulated with anti-CD3 / 28 / 2 tetramer combinations. In some forms, the Tregs are stimulated on days 0 and day 9 with transduction on days 10 & 11, or stimulation on days 0, 7, and 14 with transductions on days 15 & 16. F. Treg cells Prior to expansion and genetic modification, a source of cells can be obtained from a subject through a variety of non-limiting methods. Cells can be obtained from a number of non-limiting sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and disease sites. In some embodiments, any number of T cell lines available and known to those skilled in the art, may be used. In some embodiments, cells can be derived from a healthy donor or from a patient diagnosed with a neurodegenerative disease or condition. Accordingly, the cells in some embodiments are primary cells, e.g., primary human cells. The samples include tissue, fluid, and other samples taken directly from the subject, as well as samples resulting from one or more processing steps, such as separation, centrifugation, genetic engineering (e.g. transduction with viral vector), washing, and / or incubation. The biological sample can be a sample obtained directly from a biological source or a sample that is processed. Biological samples include, but are not limited to, body fluids, such as blood, plasma, serum, cerebrospinal fluid, synovial fluid, urine and sweat, tissue and organ samples, including processed samples derived therefrom In some aspects, the sample from which the cells are derived or isolated is blood or a blood- derived sample, or is or is derived from an apheresis product. Exemplary samples include whole blood, peripheral blood mononuclear cells (PBMCs), leukocytes, bone marrow, thymus, tissue 7545733510.1 biopsy, neural tissue, lymph node, gut associated lymphoid tissue, mucosa associated lymphoid tissue, spleen, other lymphoid tissues, liver, lung, stomach, intestine, colon, kidney, pancreas, breast, bone, prostate, cervix, testes, ovaries, tonsil, or other organ, and / or cells derived therefrom. Samples include, in the context of cell therapy, e.g., adoptive cell therapy, samples from autologous and allogeneic sources. G. Cell Purification In some embodiments, isolation of the cells includes one or more preparation and / or non- affinity based cell separation steps. In some examples, cells are washed, centrifuged, and / or incubated in the presence of one or more reagents, for example, to remove unwanted components, enrich for desired components, lyse or remove cells sensitive to particular reagents. In some examples, cells are separated based on one or more property, such as density, adherent properties, size, sensitivity and / or resistance to particular components. In some embodiments, the blood cells collected from the subject are washed, e.g., to remove the plasma fraction and to place the cells in an appropriate buffer or media for subsequent processing steps. In some embodiments, the cells are washed with phosphate buffered saline (PBS). In some embodiments, the wash solution lacks calcium and / or magnesium and / or many or all divalent cations. In some aspects, a washing step is accomplished a semi-automated "flow-through" centrifuge (for example, the Cobe 2991 cell processor, Baxter) according to the manufacturer's instructions. In some aspects, a washing step is accomplished by tangential flow filtration (TFF) according to the manufacturer's instructions. In some embodiments, the cells are resuspended in a variety of biocompatible buffers after washing, such as, for example, Ca++ / Mg++free PBS. In certain embodiments, components of a blood cell sample are removed and the cells directly resuspended in culture media. In some embodiments, the isolation methods include the separation of different cell types based on the expression or presence in the cell of one or more specific molecules, such as surface markers, e.g., surface proteins, intracellular markers, or nucleic acid. In some embodiments, the surface maker is trCD19. In some embodiments, any known method for separation based on such markers may be used. In some embodiments, the separation is affinity- or immunoaffinity-based separation. For example, the isolation in some aspects includes separation of cells and cell populations based on the cells' expression or expression level of one or more markers, typically cell surface markers, for example, by incubation with an antibody or binding partner that specifically binds to such markers, followed generally by washing steps and separation of cells having bound the antibody or binding partner, from those cells having not bound to the antibody or binding partner. 7645733510.1 Such separation steps can be based on positive selection, in which the cells having bound the reagents are retained for further use, and / or negative selection, in which the cells having not bound to the antibody or binding partner are retained. In some examples, both fractions are retained for further use. In some aspects, negative selection can be particularly useful where no antibody is available that specifically identifies a cell type in a heterogeneous population, such that separation is best carried out based on markers expressed by cells other than the desired population In some embodiments, multiple rounds of separation steps are carried out, where the positively or negatively selected fraction from one step is subjected to another separation step, such as a subsequent positive or negative selection. In some examples, a single separation step can deplete cells expressing multiple markers simultaneously, such as by incubating cells with a plurality of antibodies or binding partners, each specific for a marker targeted for negative selection. Likewise, multiple cell types can simultaneously be positively selected by incubating cells with a plurality of antibodies or binding partners expressed on the various cell types In some embodiments, isolation is carried out by enrichment for a particular cell population by positive selection, or depletion of a particular cell population, by negative selection. In some embodiments, positive or negative selection is accomplished by incubating cells with one or more antibodies or other binding agent that specifically bind to one or more surface markers expressed or expressed (marker+) at a relatively higher level (markerhigh) on the positively or negatively selected cells, respectively. In some embodiments, Tregs may be isolated, expanded, and transduced as follows: cells may be isolated from human PBMCs via a two-step negative and positive selection protocol. First, CD4+cells are isolated using negative selection, followed by a positive selection of CD25hi+cells to isolate CD4+CD25hi+Treg cells. The isolated CD4+CD25hi+Tregs may be activated with tetramers, such as anti-CD3, anti-CD28, and anti-CD2 multimers or anti-CD3 and anti-CD28 multimers (STEMCELL™ ImmunoCult) with human IL-2 (300 U / ml to 500 U / ml) over two to three weeks in culture in Treg growth medium. It has been established that the timing and method of stimulation and transduction is important for optimal Treg expansion, viability, CAR expression, and for maintenance of the Treg phenotype. In some forms, on day 9 of cell culture, Treg cells can be cryopreserved for use at a later date. The Treg cells may be activated by anti-CD3, anti-CD28, and anti-CD2 multimers, or anti- CD3 and anti-CD28 multimers on day 0 only, or day 0 and day 9, or day 0, day 7, and day 14, or other combinations of days of cell culture, generally 7 to 10 days apart. These allow different cell expansion of Tregs to be generated. In some forms, the cells are stimulated with anti-CD3, anti- CD28, and anti-CD2 tetramers, or anti-CD3 and anti-CD28 tetramer combinations on days 0 and 7745733510.1 day 9 of culture, and are transduced on days 10 & 11. In other forms, the cells are stimulated with anti-CD3, anti-CD28, and anti-CD2 tetramers, or anti-CD3 and anti-CD28 tetramer combinations on stimulation on days 0, 7, and 14, and are transduced on days 15 & 16 of culture. In some aspects, the sample or composition of cells to be separated is incubated with small, magnetizable or magnetically responsive material, such as magnetically responsive particles or microparticles, such as paramagnetic beads (e.g., such as Dynalbeads or MACS beads). The magnetically responsive material, e.g., particle, generally is directly or indirectly attached to a binding partner, e.g., an antibody, that specifically binds to a molecule, e.g., surface marker, present on the cell, cells, or population of cells that it is desired to separate, e.g., that it is desired to negatively or positively select. In some embodiments, the magnetic particle or bead includes a magnetically responsive material bound to a specific binding member, such as an antibody or other binding partner. There are many well-known magnetically responsive materials used in magnetic separation methods. Suitable magnetic particles include those described in Molday, U.S. Pat. No.4,452,773, and in European Patent Specification EP 452342 B, which are hereby incorporated by reference. Colloidal sized particles, such as those described in Owen U.S. Pat. No.4,795,698, and Liberti et al., U.S. Pat. No.5,200,084 disclose other examples of such particles. The incubation generally is carried out under conditions whereby the antibodies or binding partners, or molecules, such as secondary antibodies or other reagents, which specifically bind to such antibodies or binding partners, which are attached to the magnetic particle or bead, specifically bind to cell surface molecules if present on cells within the sample In some aspects, the sample is placed in a magnetic field, and those cells having magnetically responsive or magnetizable particles attached thereto will be attracted to the magnet and separated from the unlabeled cells. For positive selection, cells that are attracted to the magnet are retained; for negative selection, cells that are not attracted (unlabeled cells) are retained. In some aspects, a combination of positive and negative selection is performed during the same selection step, where the positive and negative fractions are retained and further processed or subject to further separation steps. In some embodiments, the magnetically responsive particles are coated in primary antibodies or other binding partners, secondary antibodies, lectins, enzymes, or streptavidin. In some embodiments, the magnetic particles are attached to cells via a coating of primary antibodies specific for one or more markers. In some embodiments, the cells, rather than the beads, are labeled with a primary antibody or binding partner, and then cell-type specific secondary antibody- or other binding partner (e.g., streptavidin)-coated magnetic particles, are added. In some embodiments, 7845733510.1 streptavidin-coated magnetic particles are used in conjunction with biotinylated primary or secondary antibodies. In some embodiments, the magnetically responsive particles are left attached to the cells that are to be subsequently incubated, cultured and / or engineered; in some aspects, the particles are left attached to the cells for administration to a patient. In some embodiments, the magnetizable or magnetically responsive particles are removed from the cells. Methods for removing magnetizable particles from cells are known and include, e.g., the use of competing non-labeled antibodies, magnetizable particles or antibodies conjugated to cleavable linkers, etc. In some embodiments, the magnetizable particles are biodegradable. In some embodiments, the isolation or separation is carried out using a system, device, or apparatus that carries out one or more of the isolation, cell preparation, separation, processing, incubation, culture, and / or formulation steps of the methods. In some aspects, the system is used to carry out each of these steps in a closed or sterile environment, for example, to minimize error, user handling and / or contamination. In one example, the system is a system as described in International Patent Application, Publication Number WO2009 / 072003, or US 20110003380 A1. In some embodiments, the system or apparatus carries out one or more, e.g., all, of the isolation, processing, engineering, and formulation steps in an integrated or self-contained system, and / or in an automated or programmable fashion. In some aspects, the system or apparatus includes a computer and / or computer program in communication with the system or apparatus, which allows a user to program, control, assess the outcome of, and / or adjust various aspects of the processing, isolation, engineering, and formulation steps. In some embodiments, a cell population described herein is collected and enriched (or depleted) via flow cytometry, in which cells stained for multiple cell surface markers are carried in a fluidic stream. In some embodiments, a cell population described herein is collected and enriched (or depleted) via preparative scale (FACS)-sorting. In some embodiments, a cell population described herein is collected and enriched (or depleted) by use of microelectromechanical systems (MEMS) chips in combination with a FACS-based detection system (see, e.g., WO 2010 / 033140, Cho et al. (2010) Lab Chip 10, 1567-1573; and Godin et al. (2008) J Biophoton.1(5):355-376. In both cases, cells can be labeled with multiple markers, such as CD4, CD25, and CD127, allowing for the isolation of well-defined T cell subsets at high purity (e.g., CD4+, CD25hi, CD127neg). In some embodiments, the antibodies or binding partners are labeled with one or more detectable marker, to facilitate separation for positive and / or negative selection. For example, separation may be based on binding to fluorescently labeled antibodies. In some examples, separation of cells based on binding of antibodies or other binding partners specific for one or more 7945733510.1 cell surface markers are carried in a fluidic stream, such as by fluorescence-activated cell sorting (FACS), including preparative scale (FACS) and / or microelectromechanical systems (MEMS) chips, e.g., in combination with a flow-cytometric detection system. Such methods allow for positive and negative selection based on multiple markers simultaneously. In some embodiments, the methods include density-based cell separation methods, such as the preparation of white blood cells from peripheral blood by lysing the red blood cells and centrifugation through a Percoll or Ficoll gradient. In any of the aforementioned separation steps, the separation need not result in 100% enrichment or removal of a particular cell population or cells expressing a particular marker. For example, positive selection of or enrichment for cells of a particular type, such as those expressing a marker, refers to increasing the number or percentage of such cells, but need not result in a complete absence of cells not expressing the marker. Likewise, negative selection, removal, or depletion of cells of a particular type, such as those expressing a marker, refers to decreasing the number or percentage of such cells, but need not result in a complete removal of all such cells. H. Cell preparation and expansion In some embodiments, the provided methods include cultivation, incubation, culture, and / or genetic engineering steps. For example, in some embodiments, provided are methods for incubating and / or engineering the depleted cell populations and culture-initiating compositions. Thus, in some embodiments, the cell populations are incubated in a culture-initiating composition. The incubation and / or engineering may be carried out in a culture vessel, such as a unit, chamber, well, column, tube, tubing set, valve, vial, culture dish, bag, or other container for culture or cultivating cells. In some embodiments, the cells are incubated and / or cultured prior to or in connection with genetic engineering. The incubation steps can include culture, cultivation, stimulation, activation, and / or propagation. In some embodiments, the compositions or cells are incubated in the presence of stimulating conditions or a stimulatory agent. Such conditions include those designed to induce proliferation, expansion, activation, and / or survival of cells in the population, to mimic antigen exposure, and / or to prime the cells for genetic engineering, such as for the introduction of a recombinant antigen receptor. The cells discussed herein can be activated and expanded, either prior to or after genetic modification of the cells, using methods as generally described, for example without limitation, in U.S. Pat. Nos.6,352,694; 6,534,055; 6,905,680; 6,692,964; 5,858,358; 6,887,466; 6,905,681; 7,144,575; 7,067,318; 7,172,869; 7,232,566; 7,175,843; 5,883,223; 6,905,874; 6,797,514; 6,867,041; and U.S. Patent Application Publication No.20060121005. The conditions can include 8045733510.1 one or more of particular media, temperature, oxygen content, carbon dioxide content, time, agents, e.g., nutrients, amino acids, antibiotics, ions, and / or stimulatory factors, such as cytokines, chemokines, antigens, binding partners, fusion proteins, recombinant soluble receptors, and any other agents designed to activate the cells. Tregs can be expanded in vitro or in vivo. In some embodiments, the isolated cells of the disclosure can be expanded by co-culturing with tissue or cells. The cells can also be expanded in vivo, for example in the subject's blood after administrating the cell into the subject. In some embodiments, the preparation methods include steps for freezing, e.g., cryopreserving, the cells, either before or after isolation, incubation, and / or engineering. In some embodiments, the freeze and subsequent thaw step removes granulocytes and, to some extent, monocytes in the cell population. In some embodiments, the cells are suspended in a freezing solution, e.g., following a washing step to remove plasma and platelets. Any of a variety of known freezing solutions and parameters in some aspects may be used. One example involves using PBS containing 20% DMSO and 8% human serum albumin (HSA), or other suitable cell freezing media. This is then diluted 1:1 with media so that the final concentration of DMSO and HSA are 10% and 4%, respectively. The cells are then frozen to -80° Celsius at a rate of 1 degree per minute and stored in the vapor phase of a liquid nitrogen storage tank. III. METHODS USING MODIFIED TREGS In exemplary embodiments, treatment of neurodegenerative diseases, conditions, and / or disorders may include administration of an effective amount of one or more modified Tregs as disclosed herein. In exemplary embodiments, treatment of a neurodegenerative disease by administering one or more types of modified Tregs according to the disclosure (e.g., wherein such Tregs may include those which express different CARS and / or NDDMs) may result in a decrease in inflammation, modulation of microglial cell activity, and / or decreased neuronal damage at the sites where the protein and / or molecular marker is expressed (i.e. diseased tissue). In exemplary embodiments, modified Tregs according to the disclosure may be administered to a patient in need of treatment, wherein the modified Tregs may be administered by intravenous injection, subcutaneous injection, intracavitary injection, intraventricular injection, intracranial injection, or intrathecally injection. Exemplary treatment methods generally include the administration of an effective amount of one or more modified Tregs, wherein such treatment including the modified Tregs may modulate local inflammation or neuronal survival. The modulation may occur, in some embodiments, by expression of specific molecules, e.g., NDMMs, e.g., anti-oxidants, e.g., neuronal growth and / or survival factors. 8145733510.1 In exemplary embodiments, modified Tregs according to the disclosure, e.g., modified Tregs including one or more CARs, may be used in a method of treating Parkinson’s disease. The modified Tregs targeted to Parkinson’s disease may include one or more CARs, wherein the one or more CARs may target α-synuclein fibrils. In some embodiments, a CAR targeted to alpha- synuclein may include a sequence of DG08. In some embodiments, a CAR targeted to alpha- synuclein may include a sequence of DG09. In some embodiments, a CAR targeted to alpha- synuclein may include a sequence of DG10. In some embodiments, a CAR targeted to alpha- synuclein may include a sequence of DG11. In some embodiments, a modified Treg may include DG08-CD28-CD3ζ, DG09-CD28-CD3ζ, DG10-CD28-CD3ζ, and / or DG11-CD28-CD3ζ, wherein each construct is targeted to alpha-synuclein. In further exemplary embodiments, modified Tregs, such as modified Tregs including one or more CARs, may be used to treat Parkinson’s disease and may target one or more neurotoxic inflammatory mediators, e.g., neurotoxic inflammatory mediations produced by activated microglia. The modified Tregs may decrease and / or inhibit microglia activation. In exemplary embodiments, modified Tregs targeting Parkinson’s disease may include targeted anti-inflammatory and neuroprotective therapeutic activity at the disease site of dopamine neuron degeneration in PD. In some embodiments, modified Tregs targeting Parkinson’s may mediate their function only at the site where α-synuclein fibrils are present. Furthermore, modified Tregs targeting Parkinson’s disease may be used in methods of treating Parkinson’s disease, wherein the modified Tregs may include one or more CARs and / or one or more NDMMs targeted to Parkinson’s disease, and further wherein the one or more CARs include single chain variable fragments such as VH and VL amino acid sequences of human and mouse monoclonal antibodies against human α-synuclein fibrils (such as, for example, amino acid sequences derived from clones NI 202.3G12, NI 202.12F4, NI 202.21D11, and mAb49 / G). In exemplary embodiments, modified Tregs targeting Parkinson’s disease may include the scFV and further include a construct including CD28-CD3ζ CAR, i.e., scFv-CD28-CD3ζ CAR, wherein the scFv is specific for human α-synuclein fibrils. Constructs including the scFv may include VH+VL and VL+VHarrangements. In exemplary embodiments, modified Tregs according to the disclosure, e.g., modified Tregs including one or more CARs, may be used in a method of treating ALS. The modified Tregs targeted to Parkinson’s disease may include one or more CARs and / or one or more NDMMs targeted to ALS. The modified Tregs may target huSOD1, e.g., the modified Tregs may include one or more CARs targeted to huSOD1. In some embodiments, a CAR targeted to huSOD1 may include a sequence of DG05. In some embodiments, a CAR targeted to huSOD1 may include a sequence of DG06. In some embodiments, a CAR targeted to huSOD1 may include a sequence of DG07. In 8245733510.1 some embodiments, a modified Treg may include DG05-CD28-CD3ζ, DG06-CD28-CD3ζ, and / or DG07-CD28-CD3ζ, wherein each construct is targeted to huSOD1. In some embodiments, a modified Treg may include DG05-CD28-CD3ζ (also referred to as DG05-28-3ζ); DG05-CD28tm- DAP10-CD3ζ (also referred to as DG05-28tm-10-3ζ); DG05-CD28tm-CD44-CD3ζ (also referred to as DG05-28tm-44-3ζ); DG05-CD28tm-CD3ζ (also referred to as DG05-28tm-3ζ); DG05-CD28 (also referred to as DG05-28); and / or DG05-CD28tm (also referred to as DG05-28tm), wherein each of the constructs is targeted to huSOD1. In some embodiments, modified Tregs may become activated at sites of huSOD1-producing motor neurons and / or sites of inflammation thereby resulting in reduced inflammation at the disease site in methods including treatment of ALS including use of modified Tregs. In some embodiments, one or more modified Tregs may include any one or more of DG05- 28-3ζ; DG05-28tm-10-3ζ; DG05-28tm-44-3ζ; DG05-28tm-3ζ; and / or DG05-28, and the modified Tregs may produce IL-10 in response to mutant SOD1 (mutSOD1) or aggregated huSOD1 antigen. In some embodiments, one or more modified Tregs may include any one or more of DG05-28-3ζ; DG05-28tm-10-3ζ; DG05-28tm-44-3ζ; DG05-28tm-3ζ; and / or DG05-28, and the modified Tregs may produce increased levels of IL-10 in response to aggregated huSOD1 antigen as compared to modified Tregs not exposed to aggregated huSOD1. In some embodiments, one or more modified Tregs may include DG05-CD28-CD3ζ, and the modified Tregs may include increased expression of cell surface markers such as GITR, PD-1, and / or CTLA-4 in response to aggregated huSOD1 as compared to modified Tregs not exposed to aggregated huSOD1. In some embodiments, one or more modified Tregs may include DG05-CD28-CD3ζ, and the modified Tregs may produce IL-10 in response to aggregated huSOD1 antigen, e.g., huSOD1 antigen that may be found in spinal cord tissue, as compared to modified Tregs not exposed to aggregated huSOD1 antigen. In some embodiments, one or more modified Tregs may include DG05-CD28-CD3ζ, and the modified Tregs, when stimulated with mutSOD1 antigen and / or anti-CD3 antibody, may inhibit superoxide generation as compared to modified Tregs that were not stimulated with mutSOD1 antigen or anti- CD3 antibody. In some embodiments, one or more modified Tregs may include DG05-CD28- CD3ζ, and the modified Tregs, when stimulated with mutSOD1 antigen, may inhibit TNF-α production from other cells as compared to modified Tregs not stimulated with mutSOD1 antigen. In some embodiments, modified Tregs targeting ALS may be used in methods of treating ALS and may include CARs targeted to huSOD1, and in some exemplary embodiments an scFv of one or more of the CARs may be expressed extracellularly with the C-terminus of the VL fused to human CD28 hinge, transmembrane, and cytoplasmic domain, followed by a human CD3ζ cytoplasmic domain to create an anti-huSOD1-CD28-CD3ζ CAR. In some embodiments, an scFv 8345733510.1 of a CAR included by a modified Treg according to the disclosure targeting ALS may be constructed by linking heavy chain variable region and light chain variable region with a linker, such as, for example, a (G4S)3(SEQ ID NO:113) linker. In some embodiments, the C-terminus of a VL of a CAR of a modified Treg targeting ALS may be fused with human CD28 hinge, transmembrane, and cytoplasmic domain, and may be followed by a human CD3ζ cytoplasmic domain. The CAR of the modified Treg targeting ALS may e.g., be an anti-huSOD1 CAR. The CARs may trigger both primary and co-stimulation signaling upon antigen binding, e.g., binding of aggregated huSOD1 or mutSOD1. In some embodiments, a CAR expressed by the Treg may include a costimulatory domain including but not limited to including, CD3ζ alone, 4-1BB, or CD28. In some embodiments a truncated (non-signaling) human CD19 (tCD19) may also expressed in the same vector as the CARs, such as by using a 2A co-expression system, the tCD19 may serve as a way to track and purify transduced T cells. In some embodiments, methods of treating ALS may include use of modified Tregs targeted to ALS that may enter the spinal cord when administered to a patient in need of treatment. In some exemplary embodiments, modified Tregs targeted to ALS may include markers such as, for example, VLA4, LFA-1, CCR6, CXCR3 or other proteins which promote neuron survival and / or functionality and / or prolong T cell function. In exemplary embodiments, modified CARs targeted to ALS, e.g., modified Tregs including one or more anti-huSOD1 CARs, may preserve a Treg phenotype when expressing one or more CARs and / or one or more NDMMs. In exemplary embodiments, modified Tregs may express IL-10 in response to an ALS protein and / or molecular marker of disease when used in methods of treating ALS. Furthermore, methods of treating ALS according to the disclosure may include use of modified Tregs which secrete anti-inflammatory cytokines, thereby resulting in an inhibition of activated microglia and / or macrophages. The secretion may occur as a result of stimulation of one or more CARs expressed by the modified Tregs for an ALS protein and / or disease associated marker, such as mutSOD1. In some embodiments, the cytokines may include IL-10, IL-4, TGF-β. In exemplary embodiments, modified Tregs may reduce and / or prevent production of neurotoxic free radicals and inflammatory cytokines by microglia when used in methods of treating ALS. In some exemplary embodiments, modified Tregs may be used in methods of treating ALS, and the methods may result in one or more of the following as compared to a control treatment: less macrophage mediated motor neuron death; less IL-1β, IL-6, TNF-α, and / or nitric oxide; and greater amounts of IL-10, IL-4, and TGF-β. In some embodiments, a method of treating ALS may include use of modified Tregs targeting TDP-43 or C9orf72 (sC9orf72), and may achieve similar results and may be used in a similar manner as to modified Tregs targeting huSOD1. 8445733510.1 Moreover, some methods of treating ALS according to the disclosure may include use of modified Tregs, wherein the modified Tregs may include anti-huSOD1 CARs, and the modified Tregs may enter the spinal cord parenchyma, recognize accumulated, aggregated spinal huSOD1 protein, and react by producing anti-inflammatory mediators. The modified Tregs may decrease expression of inflammatory mediators (e.g. CCL2, CCL3, CCL4, TNF-α, IL1β, NOX2, IL-6) and increase expression of anti-inflammatory mediators (e.g. IL-10, IL-4, and TGF-β) when administered to a patient in need of treatment. Furthermore, modified Tregs targeted to ALS, such as modified Tregs including anti-huSOD1 CARs, may inhibit persistent and / or neurotoxic inflammation around motor neurons when used in methods of treating ALS. In some exemplary embodiments, modified Tregs, e.g., modified Tregs including one or more CARs, may be used in methods of treating Alzheimer’s disease. The modified Tregs may be targeted to proteins and / or molecular markers associated with Alzheimer’s disease. In exemplary embodiments, the modified Tregs may include one or more CARs targeted to the proteins and / or markers. In some embodiments, the protein and / or marker may include amyloid-beta (Aβ), in particular oligomeric Aβ, and / or intraneuronal tangles of twisted tau protein fibers. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG01. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG02. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG03. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG04. I In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG15. In some embodiments, a CAR targeted to amyloid beta may include a sequence of DG16. In some embodiments, a modified Treg may include DG01-CD28-CD3ζ, DG02-CD28-CD3ζ, DG03-CD28- CD3ζ, DG04-CD28-CD3ζ, DG15-CD28-CD3ζ, and / or DG16-CD28-CD3ζ wherein each construct is targeted to amyloid-beta. In some embodiments, a modified Treg may include DG03-CD28- CD3ζ (also referred to as DG03-28-3ζ); DG03-CD28tm-DAP10-CD3ζ (also referred to as DG03- 28tm-10-3ζ); DG15-CD28tm-DAP10-CD3ζ, DG16-CD28tm-DAP10-CD3ζ; DG03-CD28tm- CD44-CD3ζ (also referred to as DG03-28tm-44-3ζ), DG15-CD28tm-CD44-CD3ζ, DG16-CD28tm- CD44-CD3ζ; DG03-CD28tm-4-1-BB-CD3ζ (also referred to as DG03-28tm-BB-3ζ), DG15- CD28tm-4-1-BB-CD3ζ, DG16-CD28tm-4-1-BB-CD3ζ; DG03-CD28tm-CD3ζ (also referred to as DG03-28tm-3ζ), DG15-CD28tm-CD3ζ, DG16-CD28tm-CD3ζ, DG15-CD28tm, DG16-CD28tm; DG03-CD28 (also referred to as DG03-28), DG15-CD28, DG16-CD28; and / or DG03-CD28tm (also referred to as DG03-28tm), DG15-CD28tm, or DG16-CD28tm, wherein each of the constructs is targeted to amyloid-beta. In exemplary embodiments, CARs included by modified Tregs may be targeted to Aβ peptides, and may include anti-Aβ CARs using single chain variable fragment (scFv) 8545733510.1 sequences from antibodies, e.g., human and / or humanized antibodies, with different binding specificities to Aβ, e.g., oligomeric Aβ. In some exemplary embodiments, the scFvs may fused to human CD28 hinge, transmembrane, and cytoplasmic domains, followed by a human CD3ζ cytoplasmic domain. The CARs may trigger both primary (CD3ζ) and co-stimulatory (CD28) signaling upon antigen binding and cross-linking. In some embodiments, a truncated (non- signaling) CD19 (tCD19) may also expressed in the same vector including the CARs, such as by using a T2A co-expression system, and it may serve as a means to track and purify transduced T cells. Modified Tregs including anti-Aβ CARs used in methods of treating Alzheimer’s disease may suppress proliferation of CD3-activated allogeneic CD8+ T cells in some embodiments. Furthermore, in some embodiments, when activated with oligomeric Aβ, modified Tregs including anti-Aβ CARs may produce anti-inflammatory cytokines, e.g., IL-10 when used in methods of treating Alzheimer’s disease. Furthermore, the modified Tregs may inhibit production of pro- inflammatory mediators and may enhance phagocytic capacity of activated microglia or macrophages such as by secreting IL-10, TGF-β, and IL-4 anti-inflammatory cytokines for example when used in methods of treating Alzheimer’s disease. In some exemplary embodiments, modified Tregs including expression of a CAR specific for oligomeric Aβ may have targeted anti- inflammatory activity and neuroprotective effects in regions where oligomeric Aβ may accumulate when used in methods of treating Alzheimer’s disease. In some exemplary embodiments, modified Tregs according to the disclosure may migrate to the hippocampus, wherein oligomeric Aβ may accumulate, when used in methods of treating Alzheimer’s disease. In some embodiments, one or more modified Tregs may include any one or more of DG03- 28-3ζ, DG15-28-3ζ, or DG16-28-3ζ; DG03-28tm-10-3ζ, DG15-28tm-10-3ζ, DG16-28tm-10-3ζ; DG03-28tm-44-3ζ, DG15-28tm-44-3ζ, DG16-28tm-44-3ζ; and / or DG03-28tm-CD3ζ, DG15-28tm- CD3ζ, or DG16-28tm-CD3ζ; and the modified Tregs may produce IL-10 in response to Aβ antigen, as compared to modified Tregs that were not exposed to the Aβ antigen. In some embodiments, one or more modified Tregs may include DG03-CD28-CD3ζ, and the modified Tregs may produce increased levels of IL-10 and / or IL-4 in response to Aβ antigen, which may, for example, be measured by mRNA levels of IL-10 and / or IL-4, and / or be measured by and ELISA assay, as compared to modified Tregs that were not exposed to the Aβ antigen. In some embodiments, one or more modified Tregs may include DG03-CD28-CD3ζ, DG15-CD28-CD3ζ, or DG16-CD28-CD3ζ, and the modified Tregs may, when stimulated with Aβ antigen and / or anti-CD3 antibody, may inhibit superoxide generation as compared to modified Tregs that were not stimulated with Aβ antigen or anti-CD3 antibody. In some embodiments, one or more modified Tregs may include DG03-CD28-CD3ζ, and the modified Tregs, when stimulated with Aβ antigen and / or anti-CD3 8645733510.1 antibody, may inhibit IL-6 production as compared to modified Tregs that were not stimulated with Aβ antigen or anti-CD3 antibody. Moreover, in some exemplary embodiments, modified Tregs that may be used in methods of treating Alzheimer’s disease may include anti-Aβ CARs and may traffic and accumulate to brain regions of Aβ deposits and neuroinflammation, wherein such regions may include sites of Aβ deposits in the hippocampus and frontal cortex. In some embodiments, modified Tregs including CARs targeting Alzheimer’s may accumulate in the brain regions and may lead to increased expression of human anti-inflammatory cytokines IL-10, TGF-β, and IL4 in the regions when used in methods of treating Alzheimer’s disease. These anti-inflammatory cytokines may lead to a decrease expression of pro-inflammatory mediators and the numbers of activated microglia. In exemplary embodiments, modified Tregs including CARs targeting Alzheimer’s disease may improve memory function in a patient treated with the modified Tregs. In some embodiments, modified Tregs may include a construct for expression of the NDMM Nrf2 (Keap1 inhibitor peptide), and the modified Tregs may demonstrate cytoprotective activity, such as, for example, protection of cells from hydrogen peroxide toxicity as compared to methods of treatment that do not include use of the modified Tregs. In some embodiments, a modified Treg may include a construct for expression of the NDMM human catalase and the modified Tregs may demonstrate cytoprotective activity, such as, for example, protection of cells from hydrogen peroxide toxicity as compared to methods of treatment that do not include use of the modified Tregs. In some embodiments, a modified Treg may include a construct for expression of the NDMM BDNF and the modified Tregs may demonstrate cytoprotective activity, such as, for example, protection of cells from hydrogen peroxide toxicity as compared to methods of treatment that do not include use of the modified Tregs. In some embodiments, a modified Treg may include a construct for expression of the NDMM IGF-1 and the modified Tregs may demonstrate cytoprotective activity, such as, for example, protection of cells from hydrogen peroxide toxicity as compared to methods of treatment that do not include use of the modified Tregs. Further therapeutic applications of modified Tregs according to the disclosure are discussed in detail below. Therapeutic applications Isolated cells obtained by the methods described above, or cell lines derived from such isolated cells, can be used as a medicament in the treatment of a disease, disorder, or condition in a subject. In some embodiments, such a medicament can be used for treating a neurodegenerative disease or condition. In some embodiments, the neurodegenerative disease or condition may be Parkinson’s disease, Alzheimer’s disease, or ALS. 45733510.1 A. Cell origin For purposes of the inventive methods, wherein host cells or populations of cells are administered, the cells can be cells that are xenogeneic, allogeneic or autologous to the subject. Generally, the cells are autologous or allogeneic compared to the treated subject. In instances wherein the cells are allogeneic, preferably the cells are MHC or HLA histocompatible relative to the subject to be treated and / or are modified to impair or eliminate expression or functionality of the cells’ endogenous TCRs and / or MHCs. In some instances, allogeneic Tregs may be preferred, especially if the Tregs of the subject to be treated are diseased and / or possess some property that renders them less than ideal for therapeutic use. In some instances, allogeneic Tregs may be preferred, especially if the Tregs are obtained from healthy donors as they may better migrate or traffic to desired sites, i.e., sites of neurodegeneration or neuroinflammation within the CNS. In some embodiments, the cell therapy, e.g., adoptive T cell therapy, is carried out by autologous transfer, in which the cells are isolated and / or otherwise prepared from the subject who is to receive the cell therapy, or from a sample derived from such a subject. Thus, in some aspects, the cells are derived from a subject, e.g., patient, in need of a treatment and the cells, following isolation and processing are administered to the same subject. In some embodiments, the cell therapy, e.g., adoptive T cell therapy, is carried out by allogeneic transfer, in which the cells are isolated and / or otherwise prepared from a subject other than a subject who is to receive or who ultimately receives the cell therapy, e.g., a first subject. In such embodiments, the cells then are administered to a different subject, e.g., a second subject, of the same species. In some embodiments, the first and second subjects are genetically identical. In some embodiments, the first and second subjects are genetically similar. In some embodiments, the second subject expresses the same HLA class or supertype as the first subject. B. Subjects The subject referred to herein may be any living subject. In a preferred embodiment, the subject is a mammal. The mammal referred to herein can be any mammal. As used herein, the term "mammal" refers to any mammal, including, but not limited to, mammals of the order Rodentia, such as mice and hamsters, and mammals of the order Lagomorpha, such as rabbits. The mammals may be from the order Carnivora, including Felines (cats) and Canines (dogs). The mammals may be from the order Artiodactyla, including Bovines (cows) and Swines (pigs) or of the order Perssodactyla, including Equines (horses). The mammals may be of the order Primates, Ceboids, or Simoids (monkeys) or of the order Anthropoids (humans and apes). In some embodiments, the subject, to whom the cells, cell populations, or compositions are administered is a primate, preferably a human. In some embodiments, the primate is a monkey or an 8845733510.1 ape. The subject can be male or female and can be any suitable age, including infant, juvenile, adolescent, adult, and geriatric subjects. In some examples, the patient or subject is a validated animal model for disease, adoptive cell therapy, and / or for assessing toxic outcomes, such as cytokine release syndrome (CRS). In some embodiments, the subject has persistent or relapsed disease, e.g., following treatment with another immunotherapy and / or other therapy. In some embodiments, the administration effectively treats the subject despite the subject having become resistant to another therapy. In some embodiments, the subject has not relapsed but is determined to be at risk for relapse, such as at a high risk of relapse, and thus the compound or composition is administered prophylactically, e.g., to reduce the likelihood of or prevent relapse. In some embodiments, the methods include administration of modified Tregs including one or more CARs and / or one or more NDMMs or a composition containing the cells to a subject, tissue, or cell, such as one having, at risk for, or suspected of having a neurodegenerative disease or condition. In some embodiments, the cells, populations, and compositions are administered to a subject having the particular disease or condition to be treated, e.g., via adoptive cell therapy, such as adoptive T cell therapy. In some embodiments, the cells or compositions are administered to the subject, such as a subject having or at risk for the disease or condition. In some aspects, the methods thereby treat, e.g., ameliorate one or more symptom of the disease or condition, such as by reducing, inhibiting, or inactivating microglia cells, reducing inflammation and / or neuroinflammation, and / or decreasing neuronal death. C. Functional activity In some embodiments, the present disclosure includes a type of cellular therapy wherein isolated cells, e.g., Tregs, are genetically modified to express one or more CARs and / or one or more NDMMs against a target molecule which is expressed in a neurodegenerative disease or condition, and a modified Treg cell is infused into a subject in need thereof. Examples of such target molecules include amyloid beta 1-42, superoxide dismutase-1 (SOD-1), alpha-synuclein, hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43): chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2), Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; ataxins; P / Q-type calcium channel α1A subunit; TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron 8945733510.1 protein; cystatin C. Such administration can decrease neurodegeneration and / or neuroinflammation in a target molecule specific manner. In some embodiments, the modified Tregs can undergo in vivo expansion and can persist for an extended amount of time. Once the cells (modified Tregs) are administered to a subject (e.g., a human), the biological activity of the engineered cell populations in some aspects is measured by any of a number of known methods. Parameters to assess include specific binding of an engineered or natural Treg cell or other immune cell to antigen, in vivo, e.g., by imaging, or ex vivo, e.g., by qPCR, ELISA or flow cytometry. In some aspects the biological activity is measured by assessing clinical outcome, such as the reduction in disease symptoms, such as symptoms associated a neurodegenerative disease or condition, e.g., Alzheimer’s disease, ALS and Parkinson’s disease. D. Targets The Tregs of the present disclosure, which may include one or more CARs and / or one or more NDMMs, may be used to treat, prevent, or diagnose any conditions, disorders, or diseases involving the expression of target molecules described herein (e.g., alpha-synuclein, amyloid beta, huSOD1, or mutSOD1). For example, the disclosure also contemplates a method of treating or preventing neurodegenerative diseases or conditions that may include: Alzheimer’s disease, Parkinson’s disease, ALS, prion disease, FTD, motor neuron diseases other than ALS, Huntington’s disease, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; Icelandic hereditary cerebral hemorrhage with amyloidosis. The contemplated method includes administering modified Tregs that optionally may include one or more CARs and / or one or more NDMMs according to the present disclosure. 9045733510.1 E. Modes of administration The compositions of the present disclosure may be administered in a number of ways depending upon whether local or systemic treatment is desired. In the case of adoptive cell therapy, methods for administration of cells for adoptive cell therapy are known and may be used in connection with the provided methods and compositions. For example, adoptive T cell therapy methods are described, e.g., in US Patent Application Publication No.2003 / 0170238 to Gruenberg et al; U.S. Pat. No.4,690,915 to Rosenberg; Rosenberg (2011) Nat Rev Clin Oncol.8(10):577-85). See, e.g., Themeli et al. (2013) Nat Biotechnol.31(10): 928-933; Tsukahara et al. (2013) Biochem Biophys Res Commun 438(1): 84-9; Davila et al. (2013) PLoS ONE 8(4): e61338. Such administration may be topical, parenteral, or enteral. The compositions of the disclosure are typically suitable for parenteral administration. As used herein, "parenteral administration" of a pharmaceutical composition includes any route of administration characterized by physical breaching of a tissue of a subject and administration of the pharmaceutical composition through the breach in the tissue, thus generally resulting in the direct administration into the blood stream, into muscle, or into an internal organ. Parenteral administration thus includes, but is not limited to, administration of a pharmaceutical composition by injection of the composition, by application of the composition through a surgical incision, by application of the composition through a tissue-penetrating non-surgical wound, and the like. In particular, parenteral administration is contemplated to include, but is not limited to, subcutaneous, intraperitoneal, intramuscular, intrasternal, intravenous, intraarterial, intrathecal, intraventricular, intraurethral, intracranial, intrasynovial injection or infusions; and kidney dialytic infusion techniques. In some embodiments, parenteral administration of the compositions of the present disclosure includes subcutaneous or intraperitoneal administration. Formulations of a pharmaceutical composition suitable for parenteral administration typically generally include the active ingredient combined with a pharmaceutically acceptable carrier, such as sterile water or sterile isotonic saline. Such formulations may be prepared, packaged, or sold in a form suitable for bolus administration or for continuous administration. Injectable formulations may be prepared, packaged, or sold in unit dosage form, such as in ampoules or in multi-dose containers containing a preservative. Formulations for parenteral administration include, but are not limited to, suspensions, solutions, emulsions in oily or aqueous vehicles, pastes, and the like. Such formulations may further include one or more additional ingredients including, but not limited to, suspending, stabilizing, or dispersing agents. In some embodiments of a formulation for parenteral administration, the active ingredient is provided in dry (i.e. powder or granular) form for reconstitution with a suitable vehicle (e.g. sterile pyrogen-free 9145733510.1 water) prior to parenteral administration of the reconstituted composition. Parenteral formulations also include aqueous solutions which may contain excipients such as salts, carbohydrates and buffering agents (preferably to a pH of from 3 to 9), but, for some applications, they may be more suitably formulated as a sterile non-aqueous solution or as a dried form to be used in conjunction with a suitable vehicle such as sterile, pyrogen-free water. Exemplary parenteral administration forms include solutions or suspensions in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. Such dosage forms can be suitably buffered, if desired. Other parentally-administrable formulations which are useful include those which include the active ingredient in microcrystalline form, or in a liposomal preparation. Formulations for parenteral administration may be formulated to be immediate and / or modified release. Modified release formulations include delayed-, sustained-, pulsed-, controlled-, targeted and programmed release. The terms "oral", "enteral", "enterally", "orally", "non-parenteral", "non- parenterally", and the like, refer to administration of a compound or composition to an individual by a route or mode along the alimentary canal. Examples of "oral" routes of administration of a composition include, without limitation, swallowing liquid or solid forms of a composition from the mouth, administration of a composition through a nasojejunal or gastrostomy tube, intraduodenal administration of a composition, and rectal administration, e.g., using suppositories for the lower intestinal tract of the alimentary canal. Preferably, the formulated composition including modified Tregs is suitable for administration via injection. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids, semi- solids, monophasic compositions, multiphasic compositions (e.g., oil-in-water, water-in-oil), foams, microsponges, liposomes, nanoemulsions, aerosol foams, polymers, fullerenes, and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Compositions and formulations for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets or tablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. Compositions and formulations for parenteral, intrathecal, or intraventricular administration may include sterile aqueous solutions that may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carder compounds and other pharmaceutically acceptable carriers or excipients. Pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated 9245733510.1 from a variety of components that include, but are not limited to, preformed liquids, self- emulsifying solids and self-emulsifying semisolids. The pharmaceutical compositions of the present disclosure, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. The compositions of the present disclosure may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, aerosols, and enemas. The compositions of the present disclosure may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances that increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and / or dextran. The suspension may also contain stabilizers. In some embodiments of the present disclosure the pharmaceutical compositions may be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency of the final product. Agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical and other compositions of the present disclosure. For example, cationic lipids, such as lipofectin (U.S. Pat. No.5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (WO 97 / 30731), also enhance the cellular uptake of oligonucleotides. The compositions of the present disclosure may additionally contain other adjunct components conventionally found in pharmaceutical compositions. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present disclosure, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present disclosure. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and / or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation. 9345733510.1 Formulations including populations of modified Tregs of the present disclosure may include pharmaceutically acceptable excipient(s). Excipients included in the formulations will have different purposes depending, for example, on the modified Treg, the subpopulation of modified Tregs used, and the mode of administration. Examples of generally used excipients include, without limitation: saline, buffered saline, dextrose, water-for- infection, glycerol, ethanol, and combinations thereof, stabilizing agents, solubilizing agents and surfactants, buffers and preservatives, tonicity agents, bulking agents, and lubricating agents. The formulations including populations of the modified Tregs of the present disclosure may typically have been prepared and cultured in the absence of any non-human components, such as animal serum (e.g., bovine serum albumin). The formulation or composition may also contain more than one active ingredient useful for the particular indication, disease, or condition being treated with the binding molecules or cells, preferably those with activities complementary to the binding molecule or cell, where the respective activities do not adversely affect one another. Such active ingredients are suitably present in combination in amounts that are effective for the purpose intended. Thus, in some embodiments, the pharmaceutical composition further includes other pharmaceutically active agents or drugs, such as chemotherapeutic agents, e.g., asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, vincristine, etc. The pharmaceutical composition in some aspects can employ time-released, delayed release, and sustained release delivery systems such that the delivery of the composition occurs prior to, and with sufficient time to cause, sensitization of the site to be treated. Many types of release delivery systems are available and known. Such systems can avoid repeated administrations of the composition, thereby increasing convenience to the subject and the physician. F. Dosing The pharmaceutical composition in some embodiments contains modified Tregs of the present disclosure, e.g., Tregs including one or more CARs and / or one or more NDMMs, in amounts effective to treat or prevent the disease or condition, e.g., a neurodegenerative disease or condition, such as a therapeutically effective or prophylactically effective amount. Therapeutic or prophylactic efficacy in some embodiments is monitored by periodic assessment of treated subjects. For repeated administrations over several days or longer, depending on the condition, the treatment is repeated until a desired suppression of disease symptoms occurs. However, other dosage regimens may be useful and can be determined. The desired dosage can be delivered by a single 9445733510.1 bolus administration of the composition, by multiple bolus administrations of the composition, or by continuous infusion administration of the composition. In certain embodiments, in the context of modified Tregs, a subject is administered the range of about one million to about 100 billion cells, such as, e.g., 1 million to about 50 billion cells (e.g., about 5 million cells, about 25 million cells, about 500 million cells, about 1 billion cells, about 5 billion cells, about 20 billion cells, about 30 billion cells, about 40 billion cells, or a range defined by any two of the foregoing values), such as about 10 million to about 100 billion cells (e.g., about 20 million cells, about 30 million cells, about 40 million cells, about 60 million cells, about 70 million cells, about 80 million cells, about 90 million cells, about 10 billion cells, about 25 billion cells, about 50 billion cells, about 75 billion cells, about 90 billion cells, or a range defined by any two of the foregoing values), and in some cases about 100 million cells to about 50 billion cells (e.g., about 120 million cells, about 250 million cells, about 350 million cells, about 450 million cells, about 650 million cells, about 800 million cells, about 900 million cells, about 3 billion cells, about 30 billion cells, about 45 billion cells) or any value in between these ranges, and / or such a number of cells per kilogram of body weight of the subject. For example, in some embodiments the administration of the cells or population of cells can include administration of about 103to about 109cells per kg body weight including all integer values of cell numbers within those ranges. The cells or population of cells can be administrated in one or more doses. In some embodiments, the effective amount of cells can be administrated as a single dose. In some embodiments, the effective amount of cells can be administrated as more than one dose over a period time. Timing of administration is within the judgment of managing physician and depends on the clinical condition of the patient. The cells or population of cells may be obtained from any source, such as a blood bank or a donor. While individual needs vary, determination of optimal ranges of effective amounts of a given cell type for a particular disease or conditions within the skill of the art. An effective amount means an amount which provides a therapeutic or prophylactic benefit. The dosage administrated will be dependent upon the age, health and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment and the nature of the effect desired. In some embodiments, an effective amount of cells or composition including those cells are administrated parenterally. In some embodiments, administration can be an intravenous administration. In some embodiments, administration can be directly done by injection into the disease site. For purposes of the present disclosure, the amount or dose of modified Tregs administered should be sufficient to effect a therapeutic or prophylactic response in the subject or animal over a 9545733510.1 reasonable time frame. For example, the dose of modified Tregs should be sufficient to bind to antigen, or detect, treat or prevent disease in a period of from about 2 hours or longer, e.g., about 12 to about 24 or more hours, from the time of administration. In certain embodiments, the time period could be even longer. The dose will be determined by the efficacy of the particular modified Treg and the condition of the animal (e.g., human), as well as the body weight of the animal (e.g., human) to be treated. In some embodiments, modified Tregs according to the disclosure are administered as part of a combination treatment, such as simultaneously with or sequentially with, in any order, another therapeutic intervention known in the art. For example, modified Treg cells according to the disclosure in some embodiments are co-administered with one or more additional therapeutic agents such as an antibody, nucleic acid or small molecule or in combination with another therapeutic intervention, either simultaneously or sequentially in any order. In some contexts, the cells are co- administered with another moiety which promotes the ability of the cells to cross the BBB. In some contexts, the cells are co-administered with another therapy sufficiently close in time such that the cell populations enhance the effect of one or more additional therapeutic agents, or vice versa. In some embodiments, the cells are administered prior to the one or more additional therapeutic agents. In some embodiments, the cells are administered after to the one or more additional therapeutic agents. The invention can be further understood by the following numbered paragraphs: 1. A modified regulatory T cell (Treg) which includes one or more nucleic acid constructs encoding: (1) a chimeric antigen receptor (CAR) or a synthetic immune receptor (SIR); (2) at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA) or STAT5A-CA (STAT5A-CA); and (3) optionally a neurodegenerative disease- modifying molecule (NDMM) or disease-modifying molecule (DMM). 2. The modified Treg of claim 1, wherein: (i) the (1) and (2) and optionally (3) are encoded on the same or different constructs; (ii) expression of the (1) and (2) and optionally (3) are controlled by the same or different, inducible or constitutive promoters; (iii) the modified Treg cell inducibly or constitutively expresses at least one of IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); the CAR; and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the IL-2 or the IL-2 mutein is secretory or membrane-bound; 9645733510.1 (v) the nucleic acid construct(s) further include(s) a suicide gene, optionally on the CAR or the SIR construct, further optionally expressed under the control of an inducible promoter; and / or (vi) the modified Treg persists longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen compared to a reference modified Treg which includes a nucleic acid construct encoding the same (1) CAR or SIR but which does not include (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA), and / or an unmodified Treg. 3. The modified Treg of claims 1 or 2, including one or more of the following features: (i) the modified Treg is a human cell, a primary cell, a cell derived from a stem or stem-like cell (e.g., a hematopoietic, multipotent, or pluripotent stem cell, induced pluripotent stem (iPS) cell), or a cell line cell; (ii) the one or more nucleic acid constructs include a DNA construct or an RNA construct; (iii) the IL-2 or the IL-2 mutein is secretory; (iv) the modified Treg is CD4+, FoxP3+, CD25+, and optionally Helios+, and is CD127- or CD127lo; (v) the modified Treg produces an increased amount of a cytokine upon binding to a cognate antigen of the CAR or the SIR compared to the reference modified Treg or an unmodified Treg, optionally wherein the cytokine includes IL-10, IL-2, TGF-β, and / or IL-35; (vi) the modified Treg exhibits increased localization to and / or persistence in, the CNS compared to the reference modified Treg or an unmodified Treg; (vii) the modified Treg expresses a higher level of a CNS homing marker compared to the reference modified Treg or an unmodified Treg, optionally wherein the CNS homing marker includes LFA-1 and / or Itga4. 4. The modified Treg of any one of claims 1-3, wherein the CAR or the SIR (i) binds to an antigen, ligand or receptor which is aberrantly or overexpressed at a site of inflammation, autoimmunity, or pathologyor (ii) is specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally wherein the neurodegenerative or neuroinflammatory condition is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy 9745733510.1 body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis, preferably wherein the neurodegenerative condition includes Alzheimer’s disease, or ALS. 5. The modified Treg of any one of claims 1-4 wherein the CAR or the SIR includes a single chain variable fragment (scFv) or ligand that binds to an antigen, ligand or receptor which is aberrantly or overexpressed at a site of (i) inflammation or autoimmunity (ii) neurodegeneration or neuroinflammation. 6. The modified Treg of any of claims 1-5, wherein the CAR or the SIR specifically binds to an antigen selected from: superoxide dismutase-1 (SOD-1) optionally a mutated SOD-1 expressed during ALS; an amyloid; amyloid-beta 1-42; alpha-synuclein;; hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2); an antigen including Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C; or optionally to an amyloid protein, further optionally amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS. 7. The modified Treg of any one of claims 1-6, wherein the one or more nucleic acid constructs encode at least one NDMM or DMM, optionally classic neurotrophins such as brain- derived neurotrophic factor (BDNF) or selected from IL-4, IL-10, IL-25, IL-33, IL-37, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory 9845733510.1 activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti- oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, the Neh2 domain of Nrf2, peroxiredoxins (Prxs); activity- dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G-CSF),preferably selected from BDNF or IGF-1 or the Neh2 domain of Nrf2. 8. The modified Treg of any one of claims 1-7, wherein: (1) the CAR or the SIR; (2) the IL-2, the IL-2 mutein, the constitutively active STAT5B (STAT5B-CA), or the constitutively active STAT5A (STAT5A-CA); and (3) the NDMM or the DMM, optionally BDNF or IGF-1 or the Neh2 domain of Nrf2 are encoded from 5’ to 3’ orientation in the construct as follows: (1) CAR or SIR –(2) IL-2, IL-2 mutein, STAT5A-CA, or STAT5B-CA--(3) NDMM or DMM. 9. The modified Treg of any one of claims 1-8, including one or more of the following features: (I) the CAR includes: (i) at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4-CD3ζ, CD28, DAP10, 4-1BB, CD3ζ, and CD44, and optionally is selected from CD28-CD3ζ, DAP10- CD3ζ, CD44-CD3ζ, CD28 and CD3ζ; and / or (ii) a transmembrane (TM) region of one of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof; or (II) the SIR includes: (i) (i-1) a first polypeptide including a first variable domain, optionally a VH or a VL, and a first constant domain, optionally a TCRα constant domain and (i-2) a second 9945733510.1 polypeptide including a second variable domain, optionally a VL or a VH, and a second constant domain, optionally a TCRβ constant domain, wherein the first and second variable domains form an antige-binding domain; or (ii) (ii-1) a first polypeptide including a first constant domain, optionally a TCRα constant domain and (ii-2) a second polypeptide including a second constant domain, optionally a TCRβ constant domain, wherein at leasr one of the first and second polypeptides further includes an antigen-binding domain, optionally a scFv; optionally wherein, in (i) or (ii), the SIR further includes one or more of CD3γ, CD3ε, and / or CD3ζ. 10. The modified Treg of any one of claims 1-9, wherein the one or more nucleic acid constructs include: a retroviral construct, optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct; and / or an IL-2 minimal promoter and NFAT binding sites. 11. The modified Treg of any one of claims 1-10, wherein the one or more nucleic acid constructs encode the CAR and includes one or more of the following features: (I) the CAR includes (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain; (II) (1) the CAR includes an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) the nucleic acid constructs encode human IL-2 or a human IL-2 mutein, and (3) the nucleic acid constructs encode BDNF or IGF-1 or the Neh2 domain of Nrf2; (III) the one or more nucleic acid constructs include a construct selected from: JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A-hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A-mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5b-CA; and DG03.m28H,TM.m44cy.mZ-T2A- mSTAT5a-CA having the sequences in the informal Sequence Listing preceding the claims and / or includes a CAR DNA construct as schematically depicted in Figure 1 or Figure 2; and / or (IV) the CAR includes a heavy chain variable domain and a light chain variable domain including the six complementary determining regions (CDRs) of the heavy and light chain variable domains, respectively, of DG05, DG03, DG01, DG02, DG04, DG06, DG07, 10045733510.1 DG08, DG09, DG10 or DG11, DG15, or DG16, and preferably includes the six CDRs of DG05 or DG03, or includes DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16 having the sequences contained in the informal Sequence Listing preceding the claims. 12. A nucleic acid construct or a combination of one or more nucleic acid constructs, encoding: (1) a chimeric antigen receptor (CAR) or a synthetic immune receptor (SIR), that optionally binds to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, (2) at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or includes a constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), optionally having the sequence contained in the Sequence Listing preceding the claims, and further optionally (3) a neurodegenerative disease-modifying molecule (NDMM) or disease-modifying molecule (DMM). 13. The nucleic acid construct or the combination of one or more nucleic acid constructs of claim 12, wherein: (i) the (1) and (2) and optionally (3) may be encoded on the same or different constructs; (ii) expression of (1) and (2) and optionally (3) is controlled by the same or different, inducible or constitutive promoters; (iii) the construct(s) including (1) and (2) and optionally (3) provide(s) for inducible or constitutive expression of IL-2 and the CAR or the SIR and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the IL-2 or the IL-2 mutein is secretory or membrane-bound; and / or (v) the construct(s) when introduced into a Treg result(s) in the Treg persisting longer in the CNS and / or the spleen and / or result(s) in greater numbers of the Tregs in the CNS and / or the spleen when introduced into a subject in need thereof compared to a reference Treg that includes a construct or a set of constructs encoding the same (1) CAR or SIR but that does not include (2) an exogenous nucleic acid encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA). 14. The nucleic acid construct or the combination of one or more nucleic acid constructs of claims 12 or 13, including one or more of the following features: (i) the encoded IL-2, IL-2 mutein, constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), is human; (ii) the IL-2 or the IL-2 mutein is secretory; 10145733510.1 (iii) the nucleic acid construct(s) include(s) a DNA construct or an RNA construct; (iv) the nucleic acid construct(s) include(s) a retroviral construct, optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct, and / or include(s) an IL-2 minimal promoter and NFAT binding sites; (v) the nucleic acid construct(s) include(s) a sequence encoding one or more NFAT binding sites, optionally a sequence encoding at least 4, 6 or 8 NFAT binding sites; (vi) expression of the CAR is under the control of one or more of a viral promoter, a mammalian promoter, an LTR, an IL-2 promoter, optionally an IL-2 minimal promoter, further optionally an IL-2 minimal promoter, a T2A / P2A signal, or a IRES, optionally IRES-FGF2; and / or (vii) the nucleic acid construct(s) further include(s) a suicide gene, optionally on the CAR or the SIR construct, further optionally expressed under the control of an inducible promoter. 15. The nucleic acid construct or the combination of one or more nucleic acid constructs of any one of claims 12-14, wherein the CAR or the SIR (i) binds to antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally Alzheimer’s disease or amyotrophic lateral sclerosis (ALS), further optionally to a beta amyloid or SOD-1 polypeptide expressed in Alzheimer’s disease or ALS or (ii) is specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally wherein the neurodegenerative or neuroinflammatory condition is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld- Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with 10245733510.1 amyloidosis, preferably wherein the neurodegenerative condition includes Alzheimer’s disease or ALS. 16. The nucleic acid construct or the combination of one or more nucleic acid constructs of any one of claims 12-15, which encode(s) at least one NDMM or DMM, optionally from a classic neurotrophin optionally brain-derived neurotrophic factor (BDNF), or selected from IL-37, IL-33, IL-4, IL-10, IL-25, CCL2, or TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, the Neh2 domain of Nrf2,peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, nerve growth factors, ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte- colony stimulating factor (G-CSF), preferably selected from BDNF or IGF-1 or the Neh2 domain of Nrf2. 17. The nucleic acid construct or the set of one or more nucleic acid constructs of any one of claims 12-16, wherein: (1) the CAR or the SIR; (2) the IL-2, the IL-2 mutein, the constitutively active STAT5B (STAT5B-CA), or the constitutively active STAT5A (STAT5A-CA); and (3) the NDMM or the DMM, optionally BDNF or IGF-1 or the Neh2 domain of Nrf2, are encoded from 5’ to 3’ orientation in the construct as follows: (1) CAR or SIR –(2) IL-2, IL-2 mutein, STAT5A-CA, or STAT5B-CA -(3) NDMM or DMM. 18. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-17, wherein the CAR or the SIR includes a single chain variable fragment (scFv) or ligand which recognizes at least one aberrant protein or protein which is aberrantly expressed at a site of (i) inflammation, autoimmunity, or pathology 10345733510.1 or (ii) neurodegeneration or neuroinflammation or at a site associated with the disease, 19. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-18, wherein the CAR or the SIR specifically binds to an antigen selected from: superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS, an amyloid; beta amyloid; amyloid-beta 1-42; alpha-synuclein; superoxide dismutase-1 (SOD-1); hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP- 43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2); an antigen including Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C, optionally amyloid-beta 1-42. 20. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-19, which includes one or more of the following features: (I) the nucleic acid construct(s) encode(s) the CAR including: (i) at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4-CD3ζ, CD28, DAP10, 4-1BB and CD3ζ, and optionally includes CD28-CD3ζ or CD44-CD3ζ; and / or (ii) a transmembrane (TM) region of one of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof; or (II) the nucleic acid construct(s) encode the SIR including: (i) (i-1) a first polypeptide including a first variable domain, optionally a VH or a VL, and a first constant domain, optionally a TCRα constant domain and (i-2) a second polypeptide including a second variable domain, optionally a VL or a VH, and a second constant domain, optionally a TCRβ constant domain, wherein the first and second variable domains form an antige-binding domain; or (ii) (ii-1) a first polypeptide including a first constant domain, optionally a TCRα constant domain and (ii-2) a second polypeptide including a second constant domain, optionally a TCRβ constant domain, wherein at leasr one of the first and second polypeptides further includes an antigen-binding domain, optionally a scFv; 10445733510.1 optionally wherein, in (i) or (ii), the SIR further includes one or more of CD3γ, CD3ε, and / or CD3ζ. 21. The nucleic construct or the combination of nucleic acid constructs of any one of claims 12-20, which encodes the CAR and includes one or more of the following features: (I) the CAR includes: (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain; (II) the CAR includes an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) the nucleic acid construct(s) encode(s) human IL-2 or a human IL-2 mutein, and (3) the nucleic acid construct(s) encode(s) BDNF or IGF-1 or the Neh2 domain of Nrf2; (III) the nucleic acid construct(s) include(s) a construct selected from JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A-hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A-mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5B-CA; and DG03.m28H,TM.m44cy.mZ-T2A- mSTAT5A-CA having the sequences in the informal Sequence Listing preceding the claims and / or includes a CAR DNA construct as schematically depicted in Figure 1 or Figure 2; and / or (IV) the CAR includes a...

Claims

We claim:

1. A modified regulatory T cell (Treg) which comprises one or more nucleic acid constructs encoding: (1) a chimeric antigen receptor (CAR) or a synthetic immune receptor (SIR); (2) at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA) or STAT5A-CA (STAT5A-CA); and (3) optionally a neurodegenerative disease-modifying molecule (NDMM) or disease-modifying molecule (DMM).

2. The modified Treg of claim 1, wherein: (i) the (1) and (2) and optionally (3) are encoded on the same or different constructs; (ii) expression of the (1) and (2) and optionally (3) are controlled by the same or different, inducible or constitutive promoters; (iii) the modified Treg cell inducibly or constitutively expresses at least one of IL- 2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA); the CAR; and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the IL-2 or the IL-2 mutein is secretory or membrane-bound; (v) the nucleic acid construct(s) further comprise(s) a suicide gene, optionally on the CAR or the SIR construct, further optionally expressed under the control of an inducible promoter; and / or (vi) the modified Treg persists longer in the CNS and / or the spleen and / or results in greater numbers of the Tregs in the CNS and / or the spleen compared to a reference modified Treg which comprises a nucleic acid construct encoding the same (1) CAR or SIR but which does not comprise (2) an exogenous DNA encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA), and / or an unmodified Treg.

3. The modified Treg of claims 1 or 2, comprising one or more of the following features: (i) the modified Treg is a human cell, a primary cell, a cell derived from a stem or stem-like cell (e.g., a hematopoietic, multipotent, or pluripotent stem cell, induced pluripotent stem (iPS) cell), or a cell line cell; (ii) the one or more nucleic acid constructs comprise a DNA construct or an RNA construct; (iii) the IL-2 or the IL-2 mutein is secretory; 12645733510.1(iv) the modified Treg is CD4+, FoxP3+, CD25+, and optionally Helios+, and is CD127- or CD127lo; (v) the modified Treg produces an increased amount of a cytokine upon binding to a cognate antigen of the CAR or the SIR compared to the reference modified Treg or an unmodified Treg, optionally wherein the cytokine comprises IL-10, IL-2, TGF-β, and / or IL-35; (vi) the modified Treg exhibits increased localization to and / or persistence in, the CNS compared to the reference modified Treg or an unmodified Treg; (vii) the modified Treg expresses a higher level of a CNS homing marker compared to the reference modified Treg or an unmodified Treg, optionally wherein the CNS homing marker comprises LFA-1 and / or Itga4.

4. The modified Treg of any one of claims 1-3, wherein the CAR or the SIR (i) binds to an antigen, ligand or receptor which is aberrantly or overexpressed at a site of inflammation, autoimmunity, or pathologyor (ii) is specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally wherein the neurodegenerative or neuroinflammatory condition is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral- pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis, preferably wherein the neurodegenerative condition comprises Alzheimer’s disease, or ALS.

5. The modified Treg of any one of claims 1-4 wherein the CAR or the SIR comprises a single chain variable fragment (scFv) or ligand that binds to an antigen, ligand or 12745733510.1receptor which is aberrantly or overexpressed at a site of (i) inflammation or autoimmunity (ii) neurodegeneration or neuroinflammation.

6. The modified Treg of any of claims 1-5, wherein the CAR or the SIR specifically binds to an antigen selected from: superoxide dismutase-1 (SOD-1) optionally a mutated SOD-1 expressed during ALS; an amyloid; amyloid-beta 1-42; alpha-synuclein;; hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA- binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2); an antigen comprising Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C; or optionally to an amyloid protein, further optionally amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS.

7. The modified Treg of any one of claims 1-6, wherein the one or more nucleic acid constructs encode at least one NDMM or DMM, optionally classic neurotrophins such as brain-derived neurotrophic factor (BDNF) or selected from IL-4, IL-10, IL-25, IL-33, IL-37, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, the Neh2 domain of Nrf2, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin 12845733510.1(TPO), and Granulocyte-colony stimulating factor (G-CSF),preferably selected from BDNF or IGF-1 or the Neh2 domain of Nrf2.

8. The modified Treg of any one of claims 1-7, wherein: (1) the CAR or the SIR; (2) the IL-2, the IL-2 mutein, the constitutively active STAT5B (STAT5B-CA), or the constitutively active STAT5A (STAT5A-CA); and (3) the NDMM or the DMM, optionally BDNF or IGF-1 or the Neh2 domain of Nrf2 are encoded from 5’ to 3’ orientation in the construct as follows: (1) CAR or SIR –(2) IL-2, IL-2 mutein, STAT5A-CA, or STAT5B-CA--(3) NDMM or DMM.

9. The modified Treg of any one of claims 1-8, comprising one or more of the following features: (I) the CAR comprises: (i) at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4- CD3ζ, CD28, DAP10, 4-1BB, CD3ζ, and CD44, and optionally is selected from CD28-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CD28 and CD3ζ; and / or (ii) a transmembrane (TM) region of one of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof; or (II) the SIR comprises: (i) (i-1) a first polypeptide comprising a first variable domain, optionally a VH or a VL, and a first constant domain, optionally a TCRα constant domain and (i-2) a second polypeptide comprising a second variable domain, optionally a VL or a VH, and a second constant domain, optionally a TCRβ constant domain, wherein the first and second variable domains form an antige-binding domain; or (ii) (ii-1) a first polypeptide comprising a first constant domain, optionally a TCRα constant domain and (ii-2) a second polypeptide comprising a second constant domain, optionally a TCRβ constant domain, wherein at leasr one of the first and second polypeptides further comprises an antigen-binding domain, optionally a scFv; optionally wherein, in (i) or (ii), the SIR further comprises one or more of CD3γ, CD3ε, and / or CD3ζ. 12945733510.

110. The modified Treg of any one of claims 1-9, wherein the one or more nucleic acid constructs comprise: a retroviral construct, optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct; and / or an IL-2 minimal promoter and NFAT binding sites.

11. The modified Treg of any one of claims 1-10, wherein the one or more nucleic acid constructs encode the CAR and comprises one or more of the following features: (I) the CAR comprises (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain; (II) (1) the CAR comprises an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) the nucleic acid constructs encode human IL-2 or a human IL-2 mutein, and (3) the nucleic acid constructs encode BDNF or IGF-1 or the Neh2 domain of Nrf2; (III) the one or more nucleic acid constructs comprise a construct selected from: JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A- hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF- vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A- mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A- mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5b-CA; and DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5a-CA having the sequences in the informal Sequence Listing preceding the claims and / or comprises a CAR DNA construct as schematically depicted in Figure 1 or Figure 2; and / or (IV) the CAR comprises a heavy chain variable domain and a light chain variable domain comprising the six complementary determining regions (CDRs) of the heavy and light chain variable domains, respectively, of DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16, and preferably comprises the six CDRs of DG05 or DG03, or comprises DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16 having the sequences contained in the informal Sequence Listing preceding the claims.

12. A nucleic acid construct or a combination of one or more nucleic acid constructs, encoding: (1) a chimeric antigen receptor (CAR) or a synthetic immune receptor (SIR), that optionally binds to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, (2) at least one of IL-2, an IL-2 mutein, 13045733510.1optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or comprises a constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), optionally having the sequence contained in the Sequence Listing preceding the claims, and further optionally (3) a neurodegenerative disease-modifying molecule (NDMM) or disease-modifying molecule (DMM).

13. The nucleic acid construct or the combination of one or more nucleic acid constructs of claim 12, wherein: (i) the (1) and (2) and optionally (3) may be encoded on the same or different constructs; (ii) expression of (1) and (2) and optionally (3) is controlled by the same or different, inducible or constitutive promoters; (iii) the construct(s) comprising (1) and (2) and optionally (3) provide(s) for inducible or constitutive expression of IL-2 and the CAR or the SIR and optionally a DMM or NDMM when introduced into a subject in need thereof; (iv) the IL-2 or the IL-2 mutein is secretory or membrane-bound; and / or (v) the construct(s) when introduced into a Treg result(s) in the Treg persisting longer in the CNS and / or the spleen and / or result(s) in greater numbers of the Tregs in the CNS and / or the spleen when introduced into a subject in need thereof compared to a reference Treg that comprises a construct or a set of constructs encoding the same (1) CAR or SIR but that does not comprise (2) an exogenous nucleic acid encoding IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or constitutively active STAT5A (STAT5A-CA).

14. The nucleic acid construct or the combination of one or more nucleic acid constructs of claims 12 or 13, comprising one or more of the following features: (i) the encoded IL-2, IL-2 mutein, constitutively active STAT5B (STAT5B-CA), or constitutively active STAT5A (STAT5A-CA), is human; (ii) the IL-2 or the IL-2 mutein is secretory; (iii) the nucleic acid construct(s) comprise(s) a DNA construct or an RNA construct; (iv) the nucleic acid construct(s) comprise(s) a retroviral construct, optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct, and / or comprise(s) an IL-2 minimal promoter and NFAT binding sites; 13145733510.1(v) the nucleic acid construct(s) comprise(s) a sequence encoding one or more NFAT binding sites, optionally a sequence encoding at least 4, 6 or 8 NFAT binding sites; (vi) expression of the CAR is under the control of one or more of a viral promoter, a mammalian promoter, an LTR, an IL-2 promoter, optionally an IL-2 minimal promoter, further optionally an IL-2 minimal promoter, a T2A / P2A signal, or a IRES, optionally IRES-FGF2; and / or (vii) the nucleic acid construct(s) further comprise(s) a suicide gene, optionally on the CAR or the SIR construct, further optionally expressed under the control of an inducible promoter.

15. The nucleic acid construct or the combination of one or more nucleic acid constructs of any one of claims 12-14, wherein the CAR or the SIR (i) binds to antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally Alzheimer’s disease or amyotrophic lateral sclerosis (ALS), further optionally to a beta amyloid or SOD-1 polypeptide expressed in Alzheimer’s disease or ALS or (ii) is specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally wherein the neurodegenerative or neuroinflammatory condition is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, ALS, motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral- pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis, preferably wherein the neurodegenerative condition comprises Alzheimer’s disease or ALS. 13245733510.

116. The nucleic acid construct or the combination of one or more nucleic acid constructs of any one of claims 12-15, which encode(s) at least one NDMM or DMM, optionally from a classic neurotrophin optionally brain-derived neurotrophic factor (BDNF), or selected from IL-37, IL-33, IL-4, IL-10, IL-25, CCL2, or TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO- 1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, the Neh2 domain of Nrf2,peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, nerve growth factors, ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G- CSF), preferably selected from BDNF or IGF-1 or the Neh2 domain of Nrf2.

17. The nucleic acid construct or the set of one or more nucleic acid constructs of any one of claims 12-16, wherein: (1) the CAR or the SIR; (2) the IL-2, the IL-2 mutein, the constitutively active STAT5B (STAT5B-CA), or the constitutively active STAT5A (STAT5A-CA); and (3) the NDMM or the DMM, optionally BDNF or IGF-1 or the Neh2 domain of Nrf2, are encoded from 5’ to 3’ orientation in the construct as follows: (1) CAR or SIR –(2) IL-2, IL-2 mutein, STAT5A-CA, or STAT5B-CA -(3) NDMM or DMM.

18. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-17, wherein the CAR or the SIR comprises a single chain variable fragment (scFv) or ligand which recognizes at least one aberrant protein or protein which is aberrantly expressed at a site of (i) inflammation, autoimmunity, or pathology 13345733510.1or (ii) neurodegeneration or neuroinflammation or at a site associated with the disease, 19. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-18, wherein the CAR or the SIR specifically binds to an antigen selected from: superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS, an amyloid; beta amyloid; amyloid-beta 1-42; alpha-synuclein; superoxide dismutase-1 (SOD-1); hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ- Synuclein; RNA-binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2); an antigen comprising Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C, optionally amyloid-beta 1-42.

20. The nucleic acid construct or the combination of nucleic acid constructs of any one of claims 12-19, which comprises one or more of the following features: (I) the nucleic acid construct(s) encode(s) the CAR comprising: (i) at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4- CD3ζ, CD28, DAP10, 4-1BB and CD3ζ, and optionally comprises CD28-CD3ζ or CD44-CD3ζ; and / or (ii) a transmembrane (TM) region of one of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof; or (II) the nucleic acid construct(s) encode the SIR comprising: (i) (i-1) a first polypeptide comprising a first variable domain, optionally a VH or a VL, and a first constant domain, optionally a TCRα constant domain and (i-2) a second polypeptide comprising a second variable domain, optionally a VL or a VH, and a second constant domain, optionally a TCRβ constant domain, wherein the first and second variable domains form an antige-binding domain; or (ii) (ii-1) a first polypeptide comprising a first constant domain, optionally a TCRα constant domain and (ii-2) a second polypeptide comprising a second constant 13445733510.1domain, optionally a TCRβ constant domain, wherein at leasr one of the first and second polypeptides further comprises an antigen-binding domain, optionally a scFv; optionally wherein, in (i) or (ii), the SIR further comprises one or more of CD3γ, CD3ε, and / or CD3ζ.

21. The nucleic construct or the combination of nucleic acid constructs of any one of claims 12-20, which encodes the CAR and comprises one or more of the following features: (I) the CAR comprises: (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain; (II) the CAR comprises an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) the nucleic acid construct(s) encode(s) human IL-2 or a human IL-2 mutein, and (3) the nucleic acid construct(s) encode(s) BDNF or IGF-1 or the Neh2 domain of Nrf2; (III) the nucleic acid construct(s) comprise(s) a construct selected from JC219 DG03.28.z-T2A-hIL2; JC220 DG03.44.z-T2A-hIL2; JC218 DG05.28.z-T2A-hIL2; JC221 DG05.28.Z-T2A-BDNF-P2A-hIL2; JC224 DG05.28z-T2A-BDNF-vcIRES.hIL2; JC225 DG05.28.z-T2A-hIL2-P2A-BDNF; JC228 DG03.m28.mZ-T2A-mIL2; JC229 DG03.h28.h44.hZ-T2A-mIL-2; JC230 DG03.m28H,TM.m44cy.mZ-T2A-mIL-2; JC232 DG03.m28H,TM.m44cy.mZ-T2A-mSTAT5B-CA; and DG03.m28H,TM.m44cy.mZ- T2A-mSTAT5A-CA having the sequences in the informal Sequence Listing preceding the claims and / or comprises a CAR DNA construct as schematically depicted in Figure 1 or Figure 2; and / or (IV) the CAR comprises a heavy chain variable domain and a light chain variable domain comprising the six complementary determining regions (CDRs) of the heavy and light chain variable domains, respectively, of DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16, and preferably comprises the six CDRs of DG05 or DG03, or comprises DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16 having the sequences contained in the informal Sequence Listing preceding the claims. 13545733510.

122. A method of treating a neuroinflammatory or neurodegenerative disease in a subject in need thereof which comprises introducing into the subject an effective amount of Tregs according to any one of claims 1-11.

23. A method of treating a neuroinflammatory or neurodegenerative disease in a subject in need thereof which comprises introducing into the subject (i) an effective amount of a modified regulatory T cell (Treg) which comprises one or more nucleic acid constructs encoding: (1) a chimeric antigen receptor (CAR) or a synthetic immune receptor (SIR); (2) optionally a neurodegenerative disease-modifying molecule (NDMM) or disease-modifying molecule (DMM) (ii) at least one of IL-2, an IL-2 mutein, optionally one of the IL-2 muteins having the sequences contained in the Sequence Listing preceding the claims, or constitutively active STAT5B (STAT5B-CA) or STAT5A-CA (STAT5A-CA).

24. The method of claim 23, wherein the IL-2, an IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or STAT5A-CA (STAT5A-CA) is introduced into the subject as a polypeptide or nucleic acid encoding the polypeptide, optionally administered to the subject by systemic injection or infusion.

25. The method of claims 23 or 24, wherein the modified Treg comprises one or more of the following features: (i) the modified Treg is a human cell, a primary cell, a cell derived from a stem or stem-like cell (e.g., a hematopoietic, multipotent, or pluripotent stem cell, induced pluripotent stem (iPS) cell), or a cell line cell; (ii) the one or more nucleic acid constructs comprise a DNA construct or an RNA construct; (iii) the modified Treg is CD4+, FoxP3+, CD25+, and optionally Helios+, and is CD127- or CD127lo; (iv) the modified Treg exhibits increased localization to and / or persistence in, the CNS compared to the reference modified Treg or an unmodified Treg and / or when the subject is not co-administered the IL-2, IL-2 mutein or constitutively active STAT5B (STAT5B-CA) or STAT5A-CA (STAT5A-CA); 26. The method of any one of claims 23-25, wherein the CAR or the SIR (i) binds to an antigen, ligand or receptor which is aberrantly or overexpressed at a site of inflammation, autoimmunity, or pathology or (ii) is specific to an antigen, ligand or receptor aberrantly or overexpressed in a neurodegenerative or neuroinflammatory condition, optionally wherein the neurodegenerative or neuroinflammatory condition is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease 13645733510.1related disorders, prion disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler-Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral- pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis, preferably wherein the neurodegenerative condition comprises Alzheimer’s disease, or ALS.

27. The method of any one of claims 23-26 wherein the CAR or the SIR comprises a single chain variable fragment (scFv) or ligand that binds to an antigen, ligand or receptor which is aberrantly or overexpressed at a site of (i) inflammation or autoimmunity (ii) neurodegeneration or neuroinflammation.

28. The method of any one of claims 23-27, wherein the CAR or the SIR specifically binds to an antigen selected from: superoxide dismutase-1 (SOD-1) optionally a mutated SOD-1 expressed during ALS; an amyloid; amyloid-beta 1-42; alpha-synuclein;; hyperphosphorylated tau protein; TAR DNA-binding protein 43 (TDP-43); phosphorylated TDP-43; chromosome 9 open reading frame 72 (c9orf72); β-Synuclein; γ-Synuclein; RNA- binding protein fused in sarcoma (FUS); ubiquitin; ubiquilin-2, p62; optineurin; ataxin-2; parkin; Serine / threonine-protein kinase PINK1; Leucine-rich repeat serine / threonine-protein kinase 2 (LRRK2); an antigen comprising Huntingtin with tandem glutamine repeats; prion proteins; transthyretin; dentatorubral pallidoluysian atrophy (DRPLA) protein; androgen receptor; an ataxin; a P / Q-type calcium channel α1A subunit; a TATA-box-binding protein; glial fibrillary acidic protein; DNA excision repair protein ERCC-6; survival motor neuron protein; and cystatin C; or optionally to an amyloid protein, further optionally amyloid-beta 1-42 or to superoxide dismutase-1 (SOD-1), further optionally a mutated SOD-1 expressed during ALS. 13745733510.

129. The method of any one of claims 23-28, wherein the one or more nucleic acid constructs encode at least one NDMM or DMM, optionally classic neurotrophins such as brain-derived neurotrophic factor (BDNF) or selected from IL-4, IL-10, IL-25, IL-33, IL-37, CCL2, TNFAIP3, and other molecules capable of altering the expression level, activation status, or function of a disease-associated protein; a cytokine, a molecule that prevent oxidative / inflammatory activity, a molecule that promotes neuronal growth and / or survival, a pro-neuronal factor, an anti-oxidants, a nerve growth factor, a non-classical neurotrophic factor, interleukin-1 receptor antagonist (IL-1ra); interleukin-6 (IL-6); activated protein C (APC); thrombomodulin; tissue plasminogen activator (tPA); Protein deglycase DJ-1; tissue inhibitor of metalloproteinases (TIMPs), HO-1, Ferritin, Glutathione reductase, Glutathione peroxidase, Ferritin (H), Metallothionein I, Thioredoxin, Thioredoxin reductase, Peroxiredoxin MSP23, Cu / Zn superoxide dismutase, Catalase, NRF2 activity, the Neh2 domain of Nrf2, peroxiredoxins (Prxs); activity-dependent neuroprotector homeobox (ADNP); phycocyanin; neuroglobin, ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF); insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), Fibroblast Growth Factors (FGF), Hepatocyte Growth Factor (HGF), Bone Morphogenetic Proteins (BMPs), Erythropoietin (EPO), Thrombopoietin (TPO), and Granulocyte-colony stimulating factor (G-CSF),preferably selected from BDNF or IGF-1 or the Neh2 domain of Nrf2.

30. The method of any one of claims 23-29, comprising one or more of the following features: (I) the CAR comprises: (i) at least one signaling domain, e.g., a costimulatory domain, optionally selected from CD28-CD3ζ, 4-1BB-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CTLA4- CD3ζ, CD28, DAP10, 4-1BB, CD3ζ, and CD44, and optionally is selected from CD28-CD3ζ, DAP10-CD3ζ, CD44-CD3ζ, CD28 and CD3ζ; and / or (ii) a transmembrane (TM) region of one of CD28, CD3ε, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, Dap10, CD44, CTLA-4, TCR α, TCRβ, or CD3 zeta and / or functional variants thereof; or (II) the SIR comprises: (i) (i-1) a first polypeptide comprising a first variable domain, optionally a VH or a VL, and a first constant domain, optionally a TCRα constant domain and (i-2) a second polypeptide comprising a second variable domain, optionally a VL or a VH, 13845733510.1and a second constant domain, optionally a TCRβ constant domain, wherein the first and second variable domains form an antige-binding domain; or (ii) (ii-1) a first polypeptide comprising a first constant domain, optionally a TCRα constant domain and (ii-2) a second polypeptide comprising a second constant domain, optionally a TCRβ constant domain, wherein at leasr one of the first and second polypeptides further comprises an antigen-binding domain, optionally a scFv; optionally wherein, in (i) or (ii), the SIR further comprises one or more of CD3γ, CD3ε, and / or CD3ζ.

31. The method of any one of claims 23-30, wherein the one or more nucleic acid constructs comprise: a retroviral construct, optionally a Recombinant Moloney murine leukemia virus (MMLV) retroviral construct; and / or an IL-2 minimal promoter and NFAT binding sites.

32. The modified Treg of any one of claims 23-31, wherein the one or more nucleic acid constructs encode the CAR and comprises one or more of the following features: (I) the CAR comprises (i) a CD44 costimulatory domain or CD44 intracellular domain, wherein the CD44 costimulatory domain or CD44 intracellular domain is intervened by a (ii) transmembrane region and (iii) a signaling domain or intracellular signaling domain (ICS domain), optionally a cytoplasmic CD3zeta domain; (II) (1) the CAR comprises an scFv which binds to an amyloid protein aberrantly expressed in Alzheimer’s disease or to a SOD-1 expressed during ALS, (2) the nucleic acid constructs encode BDNF or IGF-1 or the Neh2 domain of Nrf2; (III) the CAR comprises a heavy chain variable domain and a light chain variable domain comprising the six complementary determining regions (CDRs) of the heavy and light chain variable domains, respectively, of DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16, and preferably comprises the six CDRs of DG05 or DG03, or comprises DG05, DG03, DG01, DG02, DG04, DG06, DG07, DG08, DG09, DG10 or DG11, DG15, or DG16 having the sequences contained in the informal Sequence Listing preceding the claims; 33. The method of any one of claims 22-32, wherein the neuroinflammatory or neurodegenerative disease is selected from Alzheimer’s disease and other dementias, Parkinson’s disease and other Parkinson’s disease related disorders, prion disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases other than ALS, Huntington’s disease, FTD, Spinocerebellar ataxia (SCA), Spinal muscular atrophy (SMA), Friedreich's ataxia, Lewy body disease, epilepsy, multiple sclerosis, encephalitis, hydrocephalus, stroke, 13945733510.1chronic traumatic encephalopathy (CTE); synucleinopathies; tauopathies; spongiform encephalopathies; familial amyloidotic polyneuropathy; Dutch hereditary cerebral hemorrhage with amyloidosis; congophilic angiopathy; corticobasal degeneration; Pick’s disease; progressive supranuclear palsy; Creutzfeld-Jacob disease; Gerstmann-Sträussler- Schneiker syndrome; fatal familial insomnia; kuru; bovine spongiform encephalopathy; scrapie; chronic wasting disease; Lewy body variant of Alzheimer’s disease; diffuse Lewy body disease; dementia with Lewy bodies; multiple system atrophy; neurodegeneration with brain iron accumulation type I; diffuse Lewy body disease; frontotemporal lobar degeneration; hereditary dentatorubral-pallidoluysian atrophy; Kennedy’s disease; Alexander’s disease; Cockayne syndrome; and Icelandic hereditary cerebral hemorrhage with amyloidosis,preferably Alzheimer’s disease or ALS.

34. The method of any one of claims 22-33, wherein the Tregs are: (i) produced in vitro and optionally expanded prior to administration; (ii) administered via one or more of intravenous (IV), intra-cisterna magna (ICM), intracerebroventricular (ICV) or intrathecal routes; (iii) administered intravenously; and / or (iv) administered fresh or as frozen / thawed cells.

35. The method of any one of claims 22-44, wherein: (i) the subject is additionally treated with low dose IL-2, optionally weekly or monthly; (ii) the dose of Tregs ranges from about 0.5 x 106Tregs / kg up to about 30 x 106Tregs / kg; and / or (iii) the dose of Tregs ranges from 30 x 106cells to about 3x 109cells, optionally for 60kg to 100kg patients.

36. The method of any one of claims 22-35, wherein the subject: (i) has or is taking one or more AD medications, optionally selected from Galantamine, rivastigmine, donepezil and other cholinesterase inhibitors, memantine, Crenezumab, Bapineuzumab, Donanemab, Huperzine A, Lecanemab, protolitin, ponezumab, Sodium oligomannate, or Solanezumab; (ii) has a gene defect correlated with AD, optionally a mutation of amyloid precursor protein (APP) gene comprised on chromosome 21, a mutation of Presenilin 1 (PSEN1) on chromosome 14, a mutation of Presenilin 2 (PSEN2) on chromosome 1, or comprises at least one copy of APOE-e4; and / or (iii) has early onset AD or late-onset AD. 14045733510.

137. The method of any one of claims 22-36, wherein the levels and / or ratios of inflammatory cytokines or mediators, optionally one or more of IL-4, IL-10, TNFα, CCL4, NOX2, Il-1β, and IL-6 are detected, optionally wherein the detected levels and / or ratios of inflammatory cytokines or mediators, optionally one or more of IL-4, IL-10, TNFα, CCL4, NOX2, IL-1β, and IL-6, preferably IL-4 and / or IL-10, are used as part of an assessment as to whether to administer Tregs which express a CD44 costimulatory domain containing CAR or Tregs which express a CD28 or Dap10 costimulatory domain containing CAR.

38. A method of producing a modified Treg of any one of claims 1-11, the method comprising introducing a nucleic acid construct or a combination of one or more nucleic acid constructs of any one of claims 12-21 into a cell, optionally an immune cell or a cell of T cell lineage, preferably a Treg.

39. The method of claim 38, wherein the cell is or is derived from a human cell, a primary cell, a cell derived from a stem or stem-like cell (e.g., a hematopoietic, multipotent, or pluripotent stem cell, induced pluripotent stem (iPS) cell), or a cell line cell, optionally wherein the cell is: (i) a Treg isolated from cells obtained from a subject; (ii) a lymphocyte or T cell obtained from a subject; (iii) a Treg cells differentiated from a cell of T cell lineage, a double negative T cell cell, a double positive T cell, an immature CD4+ T cell, a mature CD4+ T cell, a CD4+ T cell, or a naive T cell obtained from a subject; (iv) a Treg differentiated from a stem or stem-like cell (e.g., a hematopoietic, multipotent, or pluripotent stem cell) obtained from a subject; or (v) a Treg differentiated from an iPS cell.

40. The method of claim 38 or 39, wherein the method further comprises culturing the cell: (i) in the presence of IL-2; (ii) in the presence of rapamycin; and / or (iii) for about 1-15 days.

41. A method of expanding Tregs comprising (i) stimulating CD4+, CD25hiand CD127loor CD127- cells with anti- CD3 / CD28 / CD2 tetramer complexes; (ii) optionally transfecting or transducing the cells with a nucleic acid construct.

42. The method of claim 41, wherein (i) is repeated once or twice before (ii).

43. The method of claim 42, wherein (i) is repeated on day 6, 7, 8, 9, or 10. 14145733510.

144. The method of claims 42 or 43, wherein (i) is repeated on day 13, 14, or 15.

45. The method of any one of claims 42-44, wherein (i) repeated on day 9.

46. The method of any one of claims 42-45, wherein (i) is repeated on days 7 and 14.

47. The method of any one of claims 41-46, wherein (ii) is for 1-3 days inclusive or any specific subrange or day(s) therebetween.

48. The method of claim 47, wherein (ii) occurs between days 6-20 inclusive, or any specific subrange or day therebetween.

49. The method of claim 45, wherein (ii) is on days 10 and 11.

50. The method of claim 46, wherein (ii) is on days 15 and 16.

51. The method of any one of claims 41-50, wherein cells are expanded between (i) and (ii), after (ii) or a combination thereof.

52. The method of claim 51, wherein expansion comprising culturing the cells in media optionally X-VIVO 15 medium comprising IL-2 optionally 500U / ml and / or AB serum optionally 10%.

53. The method of any one of claims 41-51, wherein the nucleic acid is the nucleic acid construct(s) of any one of claims 12-21.

54. A nucleic acid or polypeptide comprising the nucleic acid or amino acid sequence according to any one of SEQ ID NOS:1-10 or 13-23. 14245733510.1

Images