Engineered receptors for activation of regulatory t-cells

Abstract

Compositions and methods for immunotherapy are provided. In some embodiments, a composition includes an engineered regulatory T-cell (Treg), where the engineered Treg expresses a chimeric cytokine receptor (CCR). The CCR can include an activator binding domain configured to bind an activator, where the activator is an exogenous small molecule; a transmembrane domain; and an intracellular domain, where at least one of the transmembrane domain or the intracellular domain comprises or is derived from an interleukin 2 receptor (IL2R) domain.

Description

[0001]Fortem Ref. No. DCT.010WO ENGINEERED RECEPTORS FOR ACTIVATION OF REGULATORY T-CELLS CROSS-REFERENCE TO RELATED APPLICATION(S) The present application claims the benefit of priority to U.S. Provisional Application No. 63 / 656,503, filed June 5, 2024, which is incorporated by reference herein in its entirety. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The present application contains an electronic Sequence Listing in XML file format named “DCT_010WO_SL,” created on May 15, 2025, and having a size of 42.9 kilobytes, the contents of which are incorporated by reference herein in their entirety. TECHNICAL FIELD The present technology relates to immunotherapy and, in particular, to engineered receptors for activation of regulatory T-cells. BACKGROUND Regulatory T-cells (“Tregs”) are a subpopulation of T-cells having an immunomodulatory function. Due to their ability to induce immunological tolerance, Tregs have been investigated as a therapeutic option for organ transplantation and treatment of autoimmune diseases. Conventional Treg-based immunotherapies typically involve adoptive transfer of Tregs obtained from the patient or a donor. However, it can be challenging to maintain the Treg phenotype during ex vivo expansion and after administration to the patient. Moreover, many conventional Treg-based immunotherapies utilize polyclonal Tregs, which may lack sufficient specificity to the tissue of interest and produce off-target effects such as systemic immunosuppression. BRIEF DESCRIPTION OF THE DRAWINGS Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on illustrating clearly the principles of the present disclosure. FIG. 1 is a schematic illustration of an immune-activating agent directing an engineered Treg to a target cell, in accordance with embodiments of the present technology. Fortem Ref. No. DCT.010WO FIG.2A schematically illustrates examples of engineered single-chain chimeric cytokine receptors (CCRs). FIG.2B schematically illustrates an example of an engineered dual-chain CCR. FIG. 2C schematically illustrates examples of engineered single-chain CCRs with chimeric, tandem, or mutant intracellular domains. FIG. 3A schematically illustrates an example of activation of a single-chain CCR. When an immune-activating agent is not bound to the single-chain CCR (B), the single- chain CCR is undimerized with an endogenous cytokine receptor (A) (top) and the single-chain CCR is in an inactive “off” state. Upon heterodimerization with the endogenous cytokine receptor and binding of the immune-activating agent to the single-chain CCR (bottom), the single-chain CCR is turned “on,” activating intracellular signaling through the intracellular cytokine receptor domains. FIG. 3B schematically illustrates another example of activation of an engineered single-chain CCR. In the “off” state (top), when an immune-activating agent is not bound to either receptor chain of the single-chain CCR (C), the single-chain CCR remains undimerized and is inactive. Upon binding of the immune-activating agent to both receptor chains of the single-chain CCR (bottom), the receptor chains homodimerize and single-chain CCR is turned “on,” activating intracellular signaling through the intracellular cytokine receptor domains. FIG. 3C schematically illustrates an example of activation of an engineered dual-chain CCR. In the “off” state (top), when an immune-activating agent is not bound to either a first cytokine receptor chain (A) or a second cytokine receptor chain (B) of the dual- chain CCR, the chains remain undimerized and are inactive. Upon binding of the immune- activating agent to the first and second cytokine receptor chains (bottom), the first and second cytokine receptor chains heterodimerize with each other and the dual-chain CCR is turned “on,” activating intracellular signaling through the intracellular cytokine receptor domains. FIG. 4A schematically illustrates an example of a domain layout of a CCR. From N-terminus to C-terminus, a CCR may contain a signal peptide (“SP”), an activator binding domain (“ABD”), a hinge, a transmembrane domain, and an intracellular domain. FIG. 4B schematically illustrates an example of a domain layout of an engineered dual-chain CCR. Fortem Ref. No. DCT.010WO FIG. 5A is a schematic illustration of a domain layout of a construct for expression of a CCR. FIG. 5B is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR. FIG. 5C is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR and an anti-DOTA indirect CAR. FIG. 5D is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR and an anti-FITC indirect CAR. FIG. 6 schematically illustrates a process for preparation of engineered Tregs. FIG. 7 is a series of graphs illustrating purity of engineered Tregs. FIG. 8A is a series of graphs showing Treg expansion (top row) and viability (bottom row) over time at various concentrations of IL-2. FIG. 8B is a series of graphs showing Treg viability at Day 14 at various concentrations of IL-2. FIG.9A is a graph illustrating expansion of Tregs with and without the IL-2Rβγ CCR. FIG. 9B is a graph illustrating purity of Tregs with and without the IL-2Rβγ CCR. FIG.10 is a series of graphs illustrating FoxP3+Helios+ coexpression in Tregs. FIG. 11 is a graph showing Treg purity in the presence and absence of CCR activation. FIG. 12A is a series of flow cytometry plots showing expression of memory phenotype markers CD45RA and CCR7 in Tregs with and without the IL-2Rβγ CCR FIG. 12B is a graph illustrating the distribution of Treg memory phenotypes. FIGS.12C and 12D are graphs showing the prevalence of various Treg memory phenotypes. FIGS. 13A and 13B are a series of graphs showing expression of CTLA-4 in Tregs with and without the IL-2Rβγ CCR. Fortem Ref. No. DCT.010WO FIG. 14A is a series of flow cytometry plots showing expression of immunosuppressive markers PD-1 and LAG3 in Tregs. FIG. 14B provides graphs showing the percentage of Tregs expressing PD-1 and LAG3. FIGS. 14C and 14D are a series of graphs showing expression of PD-1 and LAG3 in Tregs with and without the IL-2Rβγ CCR. FIG. 15 schematically illustrates an immunosuppression assay for assessing Treg function. FIG. 16 provides flow cytometry plots illustrating an example of conventional T cell (Tconv) proliferation monitored by CellTraceViolet dilution and impact of Treg- mediated suppression of Tconv proliferation. FIG. 17 is a series of graphs showing Treg suppression of conventional T cell proliferation for Tregs with and without the IL-2Rβγ CCR. FIG. 18 is a series of graphs showing Treg viability in an immunosuppression assay. DETAILED DESCRIPTION The present technology provides compositions for use in immunotherapy, such as regulatory T-cell therapy, and associated methods. In some embodiments, for example, a composition for immunotherapy includes an engineered regulatory T-cell (Treg), where the engineered Treg expresses a chimeric cytokine receptor (CCR). The CCR can include an activator binding domain configured to bind an activator (e.g., an exogenous small molecule), a transmembrane domain, and an intracellular domain. Binding of the activator to the activator binding domain can elicit intracellular signaling that causes activation of Treg activity, such as maintenance of Treg phenotype and / or upregulation of immunosuppressive function. In some embodiments, the transmembrane and / or intracellular domains of the CCR are based on the transmembrane and / or intracellular domains of the interleukin 2 receptor (IL2R), respectively. The engineered Tregs described herein may be administered to a subject in conjunction with an immune-activating agent including the activator coupled to a targeting moiety. The targeting moiety can bind to a marker on a target cell, such as an autoantigen on a normal cell or on a cell of transplanted tissue or organ of the subject, or an antigen expressed by an inflammatory immune cell that is activated against an autoantigen. Accordingly, the Fortem Ref. No. DCT.010WO engineered Treg may be directed to the target cell via binding of the targeting moiety to the marker on the target cell and via binding of the CCR to the activator. Moreover, the immunomodulatory function of the engineered Treg can be activated by the binding of the CCR to the activator. This approach can be used for controllable induction of Treg-mediated immune tolerance for treatment of disease or conditions such as autoimmune diseases and organ transplantation. The compositions and methods described herein can provide many advantages compared to conventional approaches to Treg therapy. For example, engineered Tregs with a CCR that can be controllably directed to a cell of interest can improve the specificity and efficacy of Treg therapy, while also avoiding undesirable side effects associated with off-target Treg activation such as systemic immunosuppression. Moreover, the CCR can be designed to activate intracellular signaling pathways that are favorable for Treg survival, maintenance of Treg phenotype, conversion to Treg memory phenotypes, etc., to provide a more durable and robust immunomodulatory effect. Embodiments of the present disclosure will be described more fully hereinafter with reference to the accompanying drawings in which example embodiments are shown. Embodiments of the claims may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. The examples set forth herein are non-limiting examples and are merely examples among other possible examples. The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed present technology. Embodiments under any one heading may be used in conjunction with embodiments under any other heading. I. Engineered Regulatory T-Cells The present technology provides regulatory T-cells (“Tregs” or “Treg cells”) that express one or more engineered receptors. Tregs are a subpopulation of T-cells that have immunomodulatory functions, such as suppressing activation of the immune system and maintaining immune tolerance to autoantigens. Characteristics of Tregs include expression of CD3, CD4, CD25, and FOXP3, and / or low or negative expression of CD127. Tregs can be categorized into natural Tregs, which develop in the thymus and are delivered to the periphery, and induced Tregs, which develop in the periphery under certain stimulation conditions. Tregs can suppress immune responses through various mechanisms, including direct interaction with other immune cells and producing immunosuppressive cytokines (e.g., interleukin 10 (IL10), Fortem Ref. No. DCT.010WO interleukin 35 (IL35), transforming growth factor-beta (TGFβ)). For instance, antigen- activated Tregs can suppress colocalized T-cells regardless of their antigen specificity via bystander suppression. Tregs can also convert T-cells into induced Tregs by secretion of immunosuppressive cytokines and / or by interactions with dendritic cells. In some embodiments, an engineered Treg of the present technology expresses at least one engineered receptor that facilitates targeting of the Treg to a target cell in a subject. The target cell can be any cell for which induction and / or maintenance of immune tolerance is desirable, such as a healthy cell of the subject, a cell of a donor tissue that has been transplanted into the subject, etc. In some embodiments, the engineered Treg is administered to the subject along with an immune-activating agent that directs the engineered Treg to the target cell. The immune-activating agent can include a targeting moiety that binds to the target cell (e.g., via recognition of a marker expressed by the target cell) and an activator that is recognized by the engineered receptor of the Treg. Accordingly, the Treg can be targeted to a tissue of interest via binding of the targeting moiety to the target cell and binding of the engineered receptor to the activator, thereby allowing the Treg to exert its immunomodulatory function at the location of the tissue. In some embodiments, binding of the activator to the engineered receptor also causes activation of Treg activity, such as maintenance of a desired phenotype (e.g., Treg phenotype), conversion to a desired phenotype (e.g., Treg memory phenotype), activation of cytokine signaling pathways (e.g., STAT5 signaling), maintenance of Treg immunosuppressive function, upregulation of immunosuppressive markers and / or cytokines (e.g., IL10, IL35, TGFβ, CTLA-4, PD-1, LAG3, GARP, CD39), and / or improved cell proliferation and survival. In some embodiments, binding of the activator to the engineered receptor causes upregulation of FOXP3, Helios, IL10, IL35, TGFβ, CTLA-4, PD-1, LAG3, and / or CCR7. FIG. 1 is a schematic illustration of an immune-activating agent 100 directing an engineered Treg 102 to a target cell 104, in accordance with embodiments of the present technology. The immune-activating agent 100 can include a targeting moiety 106 (e.g., an antibody or antibody fragment) coupled to an activator 108 (e.g., a small molecule). The targeting moiety 106 can bind to a surface marker 110 expressed by the target cell 104. The Treg 102 can express an engineered receptor 112 that binds to the activator 108 of the immune- activating agent 100. The binding interactions shown in FIG. 1 can cause activation of the immunomodulatory function of the Treg 102. Fortem Ref. No. DCT.010WO In some embodiments, the surface marker 110 is an autoantigen and the target cell 104 is a cell against which immune tolerance is desired. The autoantigen can be an antigen associated with a normal, healthy cell of a subject, or an antigen associated with a cell for which immune tolerance is otherwise desirable (e.g., a cell of a transplanted organ or tissue). For example, the autoantigen can be carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein (e.g., citrullinated vimentin), a carbamylated protein, Factor VIII (FVIII), GAD65 beta- cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. The binding interactions shown in FIG. 1 can cause activation of the Treg 102 to induce immune tolerance to the target cell 104. In some embodiments, the surface marker 110 is an inflammatory marker and the target cell 104 is an autoreactive inflammatory immune cell. For instance, the inflammatory marker can be interleukin 23 receptor (IL23R) or CD83. In such embodiments, the binding interactions shown in FIG. 1 can cause activation of the Treg 102 to suppress the activation of the target cell 104. Examples of engineered receptors that may be expressed by a Treg of the present technology are provided in Sections I.A and I.B below, examples of immune-activating agents that may be used in combination with a Treg of the present technology are provided in Section II below, and additional examples of antigens that may be recognized by an immune- activating agent of the present technology are provided in Section II below. A. Chimeric Cytokine Receptors (CCRs) In some embodiments, an engineered Treg of the present technology expresses a CCR. As described herein, a CCR (which may also be referred to as a small molecule activated receptor (SMAR)) may be engineered to activate an intracellular response (e.g., a cytokine signaling pathway) upon binding of an activator to the CCR. A CCR of the present technology may be expressed on its own or in conjunction with another receptor (e.g., a CAR) to produce an immunotherapeutic effect (e.g., an immunosuppressive effect). In some embodiments, a Treg of the present technology includes a CCR and a CAR. In some embodiments, a Treg of the present technology includes a CCR without a CAR. In some embodiments, a CCR includes an activator binding domain, a transmembrane domain, and an intracellular signaling domain. The activator binding domain may bind an activator to activate the intracellular signaling domain. In some embodiments, the Fortem Ref. No. DCT.010WO activator binding domain is a small molecule binding domain that binds a small molecule (e.g., fluorescein or a fluorescein derivative (e.g., FITC, tetraxetan (DOTA), biotin or linker-specific biotin, or MPOB). Additional examples of activators are provided in Section II below. The activation signal may be communicated through the transmembrane domain to the intracellular domain in order to convert an extracellular stimulus (e.g., binding of the activator) to an intracellular effect (e.g., activation of a cytokine signaling pathway). In some embodiments, the intracellular effect is activation of a cytokine signaling pathway that is associated with development and / or maintenance of a Treg phenotype. For instance, the intracellular effect can include activation of a STAT5 signaling pathway to upregulate and / or stabilize expression of FOXP3, which may be considered a “master” transcription factor for Tregs. STAT5 is downstream of the interleukin 2 (IL2) receptor and directly binds cis elements in the FOXP3 promoter and enhancer. Without wishing to be bound by theory, it is hypothesized that a CCR including transmembrane and / or intracellular domains derived from the IL2 receptor can activate the STAT5 signaling pathway, similar to native IL2 signaling. In some embodiments, the intracellular effect is upregulation of markers associated with Treg phenotype and / or stability, such as FOXP3 and / or Helios. In some embodiments, the intracellular effect is upregulation of immunosuppressive cytokines and / or markers, such as IL10, IL35, TGFβ, CTLA-4, PD-1, LAG3, GARP, or CD39. In some embodiments, the intracellular effect is upregulation of markers associated with Treg memory phenotypes (e.g., Treg stem cell memory (Tscm) or Treg central memory (Tcm) phenotypes), such as CCR7. In some embodiments, the CCR may further include a hinge connecting the activator binding domain to the transmembrane domain. A hinge may increase flexibility of the CCR, which may reduce spatial constraints between the activator binding domain and the activator. The CCR may further include a signal peptide to direct expression of the CCR to the endoplasmic reticulum (ER). In some embodiments, a signal peptide present at the N-terminus of the protein may direct the protein to be synthesized in the ER membrane and subsequently trafficked to the plasma membrane as a transmembrane protein. A CCR of the present technology may include a domain (e.g., an intracellular signaling domain, a transmembrane domain, a hinge, a signal peptide, or combinations thereof) derived from an endogenous cytokine receptor, such as the IL2 receptor. In some embodiments, a CCR may include a domain derived from an interleukin 2 receptor subunit α (IL2Rα), an Fortem Ref. No. DCT.010WO interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ, or combinations thereof. Examples of CCRs and their associated polynucleotide sequences are provided in Table 1. Table 1: CCRs CCR SEQ ID Sequence NO IL2Rα SEQ ID MDSYLLMWGLLTFIMVPGCQADVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNG CCR NO: 1 NTYLRWYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTLKINRVEAEDLG VYFCSQSTHVPWTFGGGTKLEIKSSADDAKKDAAKKDDAKKDDAKKDGGVKLD ETGGGLVQPGGAMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRNKPYN YETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDTGIYYCTGASYGMEYLGQG TSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD VAVAGCVFLLISVLLLSGL TWQRRQRKSRRTI IL2Rβ SEQ ID MAAPALSWRLPLLILLLPLATSWASADVVMTQTPLSLPVSLGDQASISCRSSQSLV CCR NO: 2 HSNGNTYLRWYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTLKINRVEA EDLGVYFCSQSTHVPWTFGGGTKLEIKSSADDAKKDAAKKDDAKKDDAKKDGG VKLDETGGGLVQPGGAMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRN KPYNYETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDTGIYYCTGASYGMEYL GQGTSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIPW LGHLLVGLSGAFGFIILVYLLINCRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGD VQKWLSSPFPSSSFSPGGLAPEISPLEVLERDKVTQLLLQQDKVPEPASLSSNHSLT SCFTNQGYFFFHLPDALEIEACQVYFTYDPYSEEDPDEGVAGAPTGSSPQPLQPLS GEDDAYCTFPSRDDLLLFSPSLLGGPSPPSTAPGGSGAGEERMPPSLQERVPRDWD PQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPREGVSFPWSRPPGQGEFRA LNARLPLNTDAYLSLQELQGQDPTHLV IL2Rγ SEQ ID MLKPSLPFTSLLFLQLPLLGVGDVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNG CCR NO: 3 NTYLRWYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTLKINRVEAEDLG VYFCSQSTHVPWTFGGGTKLEIKSSADDAKKDAAKKDDAKKDDAKKDGGVKLD ETGGGLVQPGGAMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRNKPYN YETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDTGIYYCTGASYGMEYLGQG TSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDVVISVG SMGLIISLLCVYFWLERTMPRIPTLKNLEDLVTEYHGNFSAWSGVSKGLAESLQPD YSERLCLVSEIPPKGGALGEGPGASPCNQHSPYWAPPCYTLKPET IL2Rβ / SEQ ID MAAPALSWRLPLLILLLPLATSWASADVVMTQTPLSLPVSLGDQASISCRSSQSLV γ CCR NO: 4 HSNGNTYLRWYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTLKINRVEA EDLGVYFCSQSTHVPWTFGGGTKLEIKSSADDAKKDAAKKDDAKKDDAKKDGG VKLDETGGGLVQPGGAMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRN KPYNYETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVEDTGIYYCTGASYGMEYL GQGTSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIPW LGHLLVGLSGAFGFIILVYLLINCRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGD VQKWLSSPFPSSSFSPGGLAPEISPLEVLERDKVTQLLLQQDKVPEPASLSSNHSLT SCFTNQGYFFFHLPDALEIEACQVYFTYDPYSEEDPDEGVAGAPTGSSPQPLQPLS GEDDAYCTFPSRDDLLLFSPSLLGGPSPPSTAPGGSGAGEERMPPSLQERVPRDWD PQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPREGVSFPWSRPPGQGEFRA LNARLPLNTDAYLSLQELQGQDPTHLVTGSGATNFSLLKQAGDVEENPGPAMLKP SLPFTSLLFLQLPLLGVGDVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLR WYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTLKINRVEAEDLGVYFCS QSTHVPWTFGGGTKLEIKSSADDAKKDAAKKDDAKKDDAKKDGGVKLDETGGG LVQPGGAMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRNKPYNYETYYS DSVKGRFTISRDDSKSSVYLQMNNLRVEDTGIYYCTGASYGMEYLGQGTSVTVST TTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDVVISVGSMGLIISL LCVYFWLERTMPRIPTLKNLEDLVTEYHGNFSAWSGVSKGLAESLQPDYSERLCL Fortem Ref. No. DCT.010WO CCR SEQ ID Sequence NO VSEIPPKGGALGEGPGASPCNQHSPYWAPPCYTLKPETGSGEGRGSLLTCGDVEEN PGPWEMPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSDGPTQQL TWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKA WQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWT HVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTM SFHLEITARPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQRALVLRRKR KRMTDPTRRF IL2Rα SEQ ID ATGGACAGCTACCTGCTGATGTGGGGCCTGCTGACCTTCATCATGGTGCCTGG CCR NO: 5 CTGTCAGGCCGACGTGGTCATGACACAGACACCTCTGAGCCTGCCTGTGTCTC TGGGAGATCAGGCCAGCATCAGCTGCAGATCTAGCCAGAGCCTGGTGCACAG CAACGGCAACACCTACCTGCGGTGGTATCTGCAGAAGCCCGGCCAGTCTCCTA AGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGTGCCCGATAGATTT TCTGGCAGCGGCTCTGGCACCGACTTCACCCTGAAGATCAATAGAGTGGAAGC CGAGGACCTGGGCGTGTACTTCTGTAGCCAGTCTACCCACGTGCCATGGACCT TTGGCGGCGGAACAAAGCTGGAAATCAAGAGCAGCGCCGACGACGCCAAGAA GGACGCCGCTAAGAAGGATGACGCCAAAAAAGACGATGCCAAAAAGGATGG CGGCGTGAAGCTGGACGAAACAGGCGGAGGACTTGTTCAGCCTGGCGGAGCC ATGAAGCTGAGCTGTGTGACCAGCGGCTTCACCTTCGGCCACTACTGGATGAA CTGGGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGTCGCCCAGTTCAGA AACAAGCCCTACAACTACGAAACCTACTACAGCGACAGCGTGAAGGGCAGAT TCACCATCAGCCGGGACGACAGCAAGTCCAGCGTGTACCTGCAGATGAACAA CCTGCGCGTGGAAGATACCGGCATCTACTACTGTACCGGCGCCAGCTACGGCA TGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTACAACAACCCCTGCT CCTCGGCCTCCTACACCAGCTCCTACAATTGCCAGCCAGCCACTGTCTCTGAG GCCCGAAGCTTGTAGACCTGCTGCAGGCGGAGCCGTGCATACAAGAGGACTG GACTTCGCCTGTGATGTGGCCGTGGCCGGATGTGTGTTTCTGCTGATCTCTGTG CTGCTGCTGAGCGGCCTGACTTGGCAAAGACGGCAGAGAAAGAGCCGGCGGA CCATCTGATAA IL2Rβ SEQ ID ATGGCTGCTCCAGCTCTGTCTTGGAGACTGCCCCTGCTGATTCTGCTGCTGCCT CCR NO: 6 CTGGCTACATCTTGGGCCTCTGCCGACGTGGTCATGACACAGACACCACTGAG CCTGCCTGTGTCTCTGGGAGATCAGGCCAGCATCAGCTGCAGATCCAGCCAGT CTCTGGTGCACAGCAACGGCAACACCTACCTGCGGTGGTATCTGCAGAAGCCC GGCCAGTCTCCTAAGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGT GCCCGATAGATTTTCTGGCAGCGGCTCTGGCACCGACTTCACCCTGAAGATCA ATAGAGTGGAAGCCGAGGACCTGGGCGTGTACTTCTGTAGCCAGTCTACCCAC GTGCCATGGACCTTTGGCGGCGGAACAAAGCTGGAAATCAAGAGCAGCGCCG ACGACGCCAAGAAGGACGCCGCTAAGAAGGATGACGCCAAAAAAGACGATG CCAAAAAGGATGGCGGCGTGAAGCTGGACGAAACAGGCGGAGGACTTGTTCA GCCTGGCGGAGCCATGAAGCTGAGCTGTGTGACCAGCGGCTTCACCTTCGGCC ACTACTGGATGAACTGGGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGT CGCCCAGTTCAGAAACAAGCCCTACAACTACGAAACCTACTACAGCGACAGC GTGAAGGGCAGATTCACCATCAGCCGGGACGACAGCAAGTCCAGCGTGTACC TGCAGATGAACAACCTGCGCGTGGAAGATACCGGCATCTACTACTGTACCGGC GCCAGCTACGGCATGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTAC AACAACCCCTGCTCCTCGGCCTCCTACACCAGCTCCTACAATTGCCAGCCAGC CACTGTCTCTGAGGCCCGAAGCTTGTAGACCTGCTGCAGGCGGAGCCGTGCAT ACAAGAGGACTGGATTTCGCCTGCGACATCCCCTGGCTGGGACATCTGCTTGT TGGACTGTCTGGCGCCTTCGGCTTCATCATCCTGGTGTATCTGCTGATCAACTG CCGGAACACAGGCCCTTGGCTGAAGAAAGTGCTGAAGTGCAACACCCCTGAT CCGAGCAAGTTCTTTAGCCAGCTGAGCAGCGAGCATGGCGGCGACGTTCAGA AATGGCTGTCTAGCCCATTTCCTAGCAGCAGCTTCAGCCCAGGTGGACTGGCC CCTGAGATTAGCCCTCTGGAAGTGCTGGAACGGGACAAAGTGACCCAGCTGCT CCTCCAGCAGGATAAGGTGCCAGAACCTGCCAGCCTGTCCAGCAATCACAGCC TGACCAGCTGCTTTACCAACCAGGGCTACTTCTTCTTCCATCTGCCTGACGCTC TGGAAATCGAGGCCTGCCAGGTGTACTTCACCTACGATCCCTACAGCGAAGAG Fortem Ref. No. DCT.010WO CCR SEQ ID Sequence NO GACCCCGATGAAGGTGTTGCTGGCGCCCCTACAGGATCTTCTCCACAGCCTCT GCAACCTCTGAGCGGCGAGGATGATGCCTACTGCACCTTTCCAAGCAGGGACG ACCTGCTCCTGTTCAGCCCATCTCTGCTCGGAGGACCATCTCCTCCATCTACAG CTCCAGGCGGATCTGGCGCTGGCGAGGAAAGAATGCCACCTAGCCTGCAAGA GCGGGTGCCCAGAGATTGGGATCCTCAACCTCTCGGCCCTCCAACACCTGGCG TGCCAGATCTCGTGGACTTTCAGCCTCCTCCAGAGCTGGTGCTGAGAGAAGCT GGCGAAGAAGTGCCAGACGCTGGCCCTAGAGAGGGCGTTAGCTTTCCTTGGA GCAGACCTCCTGGACAGGGCGAGTTTAGGGCCCTGAATGCAAGACTGCCTCTG AACACCGACGCCTACCTGTCTCTGCAAGAACTGCAGGGACAAGACCCCACAC ACCTGGTGTAATGA IL2Rγ SEQ ID ATGCTGAAGCCCAGCCTGCCTTTTACCAGCCTGCTGTTCCTGCAGCTGCCTCTG CCR NO: 7 CTTGGCGTGGGAGATGTGGTCATGACACAGACCCCACTGAGCCTGCCTGTGTC TCTGGGAGATCAGGCCAGCATCAGCTGCAGATCTAGCCAGAGCCTGGTGCACA GCAACGGCAACACCTACCTGCGGTGGTATCTGCAGAAGCCCGGCCAGTCTCCT AAGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGTGCCCGATAGATT TTCTGGCAGCGGCTCTGGCACCGACTTCACCCTGAAGATCAATAGAGTGGAAG CCGAGGACCTGGGCGTGTACTTCTGTAGCCAGTCTACCCACGTGCCATGGACC TTTGGCGGCGGAACAAAGCTGGAAATCAAGAGCAGCGCCGACGACGCCAAGA AGGACGCCGCTAAGAAGGATGACGCCAAAAAAGACGATGCCAAAAAGGATG GCGGCGTGAAGCTGGACGAAACAGGCGGAGGACTTGTTCAGCCTGGCGGAGC CATGAAGCTGAGCTGTGTGACCAGCGGCTTCACCTTCGGCCACTACTGGATGA ACTGGGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGTCGCCCAGTTCAG AAACAAGCCCTACAACTACGAAACCTACTACAGCGACAGCGTGAAGGGCAGA TTCACCATCAGCCGGGACGACAGCAAGTCCAGCGTGTACCTGCAGATGAACA ACCTGCGCGTGGAAGATACCGGCATCTACTACTGTACCGGCGCCAGCTACGGC ATGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTACAACAACCCCTGC TCCTCGGCCTCCTACACCAGCTCCTACAATTGCCAGCCAGCCACTGTCTCTGAG GCCCGAAGCTTGTAGACCTGCTGCAGGCGGAGCCGTGCATACAAGAGGACTG GACTTCGCCTGCGACGTGGTCATCTCTGTGGGCTCTATGGGCCTGATCATCTCC CTGCTGTGTGTGTACTTTTGGCTGGAACGGACCATGCCTCGGATCCCCACACTG AAGAACCTGGAAGATCTGGTCACCGAGTACCACGGCAACTTCAGTGCTTGGAG CGGCGTGTCAAAAGGACTGGCCGAAAGCCTGCAGCCTGACTACTCCGAGAGA CTGTGCCTGGTGTCTGAGATCCCTCCTAAAGGCGGCGCTCTCGGAGAAGGACC TGGTGCCTCTCCATGCAATCAGCACAGCCCTTATTGGGCCCCTCCTTGCTACAC CCTGAAACCTGAGACATGATGA IL2Rβ / SEQ ID ATGGCTGCTCCAGCTCTGTCTTGGAGACTGCCCCTGCTGATTCTGCTGCTGCCT γ CCR NO: 8 CTGGCTACATCTTGGGCCTCTGCCGACGTGGTCATGACACAGACACCACTGAG CCTGCCTGTGTCTCTGGGAGATCAGGCCAGCATCAGCTGCAGATCCAGCCAGT CTCTGGTGCACAGCAACGGCAACACCTACCTGCGGTGGTATCTGCAGAAGCCC GGCCAGTCTCCTAAGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGT GCCCGATAGATTTTCTGGCAGCGGCTCTGGCACCGACTTCACCCTGAAGATCA ATAGAGTGGAAGCCGAGGACCTGGGCGTGTACTTCTGTAGCCAGTCTACCCAC GTGCCATGGACCTTTGGCGGCGGAACAAAGCTGGAAATCAAGAGCAGCGCCG ACGACGCCAAGAAGGACGCCGCTAAGAAGGATGACGCCAAAAAAGACGATG CCAAAAAGGATGGCGGCGTGAAGCTGGACGAAACAGGCGGAGGACTTGTTCA GCCTGGCGGAGCCATGAAGCTGAGCTGTGTGACCAGCGGCTTCACCTTCGGCC ACTACTGGATGAACTGGGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGT CGCCCAGTTCAGAAACAAGCCCTACAACTACGAAACCTACTACAGCGACAGC GTGAAGGGCAGATTCACCATCAGCCGGGACGACAGCAAGTCCAGCGTGTACC TGCAGATGAACAACCTGCGCGTGGAAGATACCGGCATCTACTACTGTACCGGC GCCAGCTACGGCATGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTAC AACAACCCCTGCTCCTCGGCCTCCTACACCAGCTCCTACAATTGCCAGCCAGC CACTGTCTCTGAGGCCCGAAGCTTGTAGACCTGCTGCAGGCGGAGCCGTGCAT ACAAGAGGACTGGATTTCGCCTGCGACATCCCCTGGCTGGGACATCTGCTTGT TGGACTGTCTGGCGCCTTCGGCTTCATCATCCTGGTGTATCTGCTGATCAACTG CCGGAACACAGGCCCTTGGCTGAAGAAAGTGCTGAAGTGCAACACCCCTGAT Fortem Ref. No. DCT.010WO CCR SEQ ID Sequence NO CCGAGCAAGTTCTTTAGCCAGCTGAGCAGCGAGCATGGCGGCGACGTTCAGA AATGGCTGTCTAGCCCATTTCCTAGCAGCAGCTTCAGCCCAGGTGGACTGGCC CCTGAGATTAGCCCTCTGGAAGTGCTGGAACGGGACAAAGTGACCCAGCTGCT CCTCCAGCAGGATAAGGTGCCAGAACCTGCCAGCCTGTCCAGCAATCACAGCC TGACCAGCTGCTTTACCAACCAGGGCTACTTCTTCTTCCATCTGCCTGACGCTC TGGAAATCGAGGCCTGCCAGGTGTACTTCACCTACGATCCCTACAGCGAAGAG GACCCCGATGAAGGTGTTGCTGGCGCCCCTACAGGATCTTCTCCACAGCCTCT GCAACCTCTGAGCGGCGAGGATGATGCCTACTGCACCTTTCCAAGCAGGGACG ACCTGCTCCTGTTCAGCCCATCTCTGCTCGGAGGACCATCTCCTCCATCTACAG CTCCAGGCGGATCTGGCGCTGGCGAGGAAAGAATGCCACCTAGCCTGCAAGA GCGGGTGCCCAGAGATTGGGATCCTCAACCTCTCGGCCCTCCAACACCTGGCG TGCCAGATCTCGTGGACTTTCAGCCTCCTCCAGAGCTGGTGCTGAGAGAAGCT GGCGAAGAAGTGCCAGACGCTGGCCCTAGAGAGGGCGTTAGCTTTCCTTGGA GCAGACCTCCTGGACAGGGCGAGTTTAGGGCCCTGAATGCAAGACTGCCTCTG AACACCGACGCCTACCTGTCTCTGCAAGAACTGCAGGGACAAGACCCCACAC ACCTGGTGACTGGATCTGGAGCAACAAACTTCTCACTACTCAAACAAGCAGGT GACGTGGAGGAGAATCCCGGGCCTGCCATGCTGAAGCCCAGCCTGCCTTTTAC CAGCCTGCTGTTCCTGCAGCTGCCTCTGCTTGGCGTGGGAGATGTGGTCATGA CACAGACCCCACTGAGCCTGCCTGTGTCTCTGGGAGATCAGGCCAGCATCAGC TGCAGATCTAGCCAGAGCCTGGTGCACAGCAACGGCAACACCTACCTGCGGTG GTATCTGCAGAAGCCCGGCCAGTCTCCTAAGGTGCTGATCTACAAGGTGTCCA ACAGAGTGTCCGGCGTGCCCGATAGATTTTCTGGCAGCGGCTCTGGCACCGAC TTCACCCTGAAGATCAATAGAGTGGAAGCCGAGGACCTGGGCGTGTACTTCTG TAGCCAGTCTACCCACGTGCCATGGACCTTTGGCGGCGGAACAAAGCTGGAAA TCAAGAGCAGCGCCGACGACGCCAAGAAGGACGCCGCTAAGAAGGATGACGC CAAAAAAGACGATGCCAAAAAGGATGGCGGCGTGAAGCTGGACGAAACAGG CGGAGGACTTGTTCAGCCTGGCGGAGCCATGAAGCTGAGCTGTGTGACCAGCG GCTTCACCTTCGGCCACTACTGGATGAACTGGGTCCGACAGAGCCCTGAGAAA GGCCTGGAATGGGTCGCCCAGTTCAGAAACAAGCCCTACAACTACGAAACCT ACTACAGCGACAGCGTGAAGGGCAGATTCACCATCAGCCGGGACGACAGCAA GTCCAGCGTGTACCTGCAGATGAACAACCTGCGCGTGGAAGATACCGGCATCT ACTACTGTACCGGCGCCAGCTACGGCATGGAATATCTCGGCCAGGGCACCAGC GTGACCGTGTCTACAACAACCCCTGCTCCTCGGCCTCCTACACCAGCTCCTACA ATTGCCAGCCAGCCACTGTCTCTGAGGCCCGAAGCTTGTAGACCTGCTGCAGG CGGAGCCGTGCATACAAGAGGACTGGACTTCGCCTGCGACGTGGTCATCTCTG TGGGCTCTATGGGCCTGATCATCTCCCTGCTGTGTGTGTACTTTTGGCTGGAAC GGACCATGCCTCGGATCCCCACACTGAAGAACCTGGAAGATCTGGTCACCGAG TACCACGGCAACTTCAGTGCTTGGAGCGGCGTGTCAAAAGGACTGGCCGAAA GCCTGCAGCCTGACTACTCCGAGAGACTGTGCCTGGTGTCTGAGATCCCTCCT AAAGGCGGCGCTCTCGGAGAAGGACCTGGTGCCTCTCCATGCAATCAGCACA GCCCTTATTGGGCCCCTCCTTGCTACACCCTGAAACCTGAGACAGGCTCCGGC GAGGGCAGGGGAAGTCTTCTAACATGCGGGGACGTGGAGGAAAATCCCGGCC CATGGGAAATGCCTCCTCCTCGGCTGCTGTTCTTCCTGCTGTTTCTGACCCCTA TGGAAGTGCGGCCCGAGGAACCTCTGGTGGTCAAAGTTGAAGAGGGCGACAA CGCCGTGCTGCAGTGTCTGAAGGGCACATCTGATGGCCCCACACAGCAGCTGA CCTGGTCTAGAGAGAGCCCTCTGAAGCCCTTCCTGAAGCTGTCTCTGGGACTG CCTGGACTGGGCATCCATATGAGGCCTCTGGCCATCTGGCTGTTCATCTTCAAC GTGTCCCAGCAGATGGGCGGCTTCTACCTGTGTCAACCTGGACCTCCAAGCGA GAAGGCTTGGCAGCCTGGCTGGACCGTGAATGTGGAAGGATCCGGCGAGCTG TTCCGGTGGAATGTGTCTGATCTCGGCGGCCTCGGATGCGGCCTGAAGAATAG ATCTAGCGAGGGCCCTAGCAGCCCCAGCGGAAAACTGATGAGCCCCAAGCTG TACGTGTGGGCCAAAGACAGACCCGAGATTTGGGAGGGCGAGCCTCCTTGTCT GCCTCCTAGAGACAGCCTGAACCAGAGCCTGAGCCAGGACCTGACAATGGCC CCTGGATCTACACTGTGGCTGAGCTGTGGCGTGCCACCTGACAGTGTGTCTAG AGGCCCTCTGTCTTGGACCCACGTGCACCCTAAGGGCCCTAAGTCTCTGCTGA GCCTGGAACTGAAGGACGACAGGCCCGCCAGAGATATGTGGGTCATGGAAAC AGGCCTGCTGCTGCCTAGAGCCACAGCACAGGATGCCGGCAAGTACTACTGCC ACAGAGGCAACCTGACCATGAGCTTCCACCTGGAAATCACCGCCAGACCTGTC Fortem Ref. No. DCT.010WO CCR SEQ ID Sequence NO CTGTGGCACTGGCTGCTTAGAACCGGCGGCTGGAAAGTGTCTGCCGTGACTCT GGCCTACCTGATCTTCTGCCTGTGTAGCCTCGTGGGCATCCTGCATCTGCAGAG AGCACTGGTCCTGCGGCGGAAGCGGAAGAGAATGACCGATCCTACCAGACGG TTCTGATGA In some embodiments, a CCR may include a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 1 – SEQ ID NO: 4. In some embodiments, a CCR is encoded by a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 5 – SEQ ID NO: 8. In some embodiments, a CCR may include a sequence of any one of SEQ ID NO: 1 – SEQ ID NO: 4. In some embodiments, a CCR is encoded by a sequence of any one of SEQ ID NO: 5 – SEQ ID NO: 8. In some embodiments, a CCR may include a signal peptide of any one of SEQ ID NO: 16 – SEQ ID NO: 21, an activator binding domain of SEQ ID NO: 9, a transmembrane domain of any one of SEQ ID NO: 13 – SEQ ID NO: 15, and / or an intracellular signaling domain of any one of SEQ ID NO: 10 – SEQ ID NO: 12. In some embodiments, a CCR may further include a hinge (e.g., SEQ ID NO: 22), a cleavage sequence (e.g., any one of SEQ ID NO: 24 – SEQ ID NO: 27), a marker (e.g., SEQ ID NO: 23), or combinations thereof. In some embodiments, a CCR may be a single-chain CCR. Examples of single- chain CCRs are illustrated in FIG. 2A, and may include any one of SEQ ID NO: 1 – SEQ ID NO: 3 (based on IL2Rα, IL2Rβ, and IL2Rγ, respectively). A single-chain CCR can be derived from a single cytokine receptor chain (e.g., an α, β, or γ chain). The cytokine receptor chain may be a wild-type cytokine receptor chain, or may be a chimeric or mutant cytokine receptor chain. In some embodiments, the single cytokine receptor chain is capable of initiating signaling via dimerization with an endogenous cytokine receptor chain, e.g., as shown in FIG. 3A. Some cytokine receptor chains are capable of initiating signaling via homodimerization. Thus, in some embodiments, a pair of single-chain CCRs may bind to respective activators and homodimerize with each other to initiate intracellular signaling, e.g., as shown in FIG. 3B. Single-chain CCRs may be used to initiate novel signaling pathways by dimerization with endogenous cytokine receptor chains, depending on how the dimerization occurs and which Fortem Ref. No. DCT.010WO receptor chains are dimerized. Additionally, in some embodiments, production of viral vectors and engineered immune cells may be easier for single-chain CCRs. In some embodiments, a CCR may be a dual-chain CCR. A representative example of a dual-chain CCR is illustrated in FIG. 2B. For example, a dual-chain CCR may include a first CCR of SEQ ID NO: 2 (based on IL2Rβ) and a second CCR of SEQ ID NO: 3 (based on IL2Rγ). A dual-chain CCR can be derived from two cytokine receptor chains (e.g., a combination of α, β, or γ chains), each of which can be independently selected from any of the cytokine receptor chains described herein. For example, a dual-chain CCR including a first cytokine receptor chain derived from IL2Rβ and a second cytokine receptor chain derived from IL2Rγ can mimic the IL2-IL2R signaling pathway. In some embodiments, each chain of a dual- chain CCR may bind to a respective activator and heterodimerize with each other to activate intracellular signaling, e.g., as shown in FIG. 3C. Optionally, a dual-chain CCR can be expressed as a single protein including both cytokine receptor chains. The single protein can be subsequently cleaved (e.g., via the inclusion of a 2A peptide or other cleavage sequence) to produce the two separate cytokine receptor chains. SEQ ID NO: 4 provides an example of a dual-chain CCR that is initially expressed as a single protein. Although FIGS. 3A–3C illustrate the activator as being part of a soluble complex, this is not intended to be limiting, and in other embodiments, the activator can be attached to a surface or other substrate, as described below. In some embodiments, a CCR includes one or more cytokine receptor chains with one or more chimeric, tandem, and / or mutant intracellular domains. Representative examples of single-chain CCRs with chimeric, tandem, and / or mutant intracellular domains are shown in FIG. 1C. For example, a CCR can include a chimeric cytokine receptor chain including a first intracellular domain derived from IL2Rβ and a second intracellular domain derived from IL2Rγ (“chimeric IL2Rβ / γ” in FIG.1C). As another example, a CCR can include a tandem cytokine receptor chain including first and second intracellular domains derived from IL2Rβ (“tandem IL21Rβ / β” in FIG.1C). As yet another example, a CCR can include a mutant cytokine receptor chain including a mutant intracellular domain derived from IL2Rβ (“mutant IL21Rβ” in FIG.1C). A mutant intracellular domain can include one or more mutations relative to the wild-type intracellular domain, such as point mutations, truncations, etc. Optionally, the CCR may exhibit activity (e.g., cytokine signaling activity) without binding of an activator to the activator binding domain, referred to herein as “activator- Fortem Ref. No. DCT.010WO independent activity” or “ligand-independent activity.” Without wishing to be bound by theory, it is hypothesized that activator-independent activity may be due to dimerization of a cytokine receptor chain of a CCR with another cytokine receptor chain (e.g., of the CCR or an endogenous cytokine receptor) that occurs even in the absence of the activator. Dimerization may occur between the extracellular and / or transmembrane domains of the cytokine receptor chains. Activator-independent activity may also occur due to interactions of the CCR with other co-expressed receptors, such as a CAR. Such interactions may comprise physical interactions (e.g., dimerization) as well as interactions in downstream signaling pathways. The strength of activator-independent activity can be increased or decreased by changing the extracellular domain of the CCR, and / or by increasing or decreasing the length of the hinge between domains of the CCR. In some embodiments, activator-independent activity provides similar effects as activation of the CCR (e.g., maintenance of Treg phenotype, conversion to Treg memory phenotype, improved Treg survival and / or proliferation, enhancement of immunosuppression), but with reduced magnitude and / or shorter duration. In some embodiments, activator- independent activity primes the Treg for subsequent activation, e.g., the magnitude and / or duration of the effects following administration of the activator is greater if the Treg has previously exhibited activator-independent activity, versus a Treg that does not exhibit activator-independent activity. In some embodiments, the level of activator-independent activity exhibited by a CCR depends at least partially on the structure of the CCR. For instance, a shorter hinge may be associated with higher levels of activator-independent activity, e.g., due to enhanced dimerization facilitated by the reduced flexibility of the extracellular and / or transmembrane domains of the CCR. The shorter hinge can be no more than 30 amino acids, 25 amino acids, 20 amino acids, 15 amino acids, 10 amino acids, 9 amino acids, 8 amino acids, 7 amino acids, 6 amino acids, 5 amino acids, 4 amino acids, 3 amino acids, 2 amino acids, or 1 amino acid in length. Conversely, a longer hinge may be associated with lower levels of activator- independent activity, e.g., due to reduced dimerization attributable to the increased flexibility of the extracellular and / or transmembrane domains of the CCR. The longer hinge can be at least 20 amino acids, 25 amino acids, 30 amino acids, 35 amino acids, 40 amino acids, 45 amino acids, or 50 amino acids in length. Other structural features that may influence activator- independent activity include the size of the extracellular domain, the size of the transmembrane domain, and / or the size of the intracellular domain. Fortem Ref. No. DCT.010WO The structure of the CCR (e.g., length of the hinge) can be selected to produce a desired level of activator-independent activity. Activator-independent activity can be beneficial, for example, to provide constitutive maintenance of Treg phenotype and / or immunosuppression. Conversely, lower levels of activator-independent activity may be advantageous in situations where switchable control over immunosuppression is desired. 1. Activator Binding Domain A CCR of the present technology may include an activator binding domain. The activator binding domain may be positioned in an extracellular region of the CCR and may be designed to bind an activator (e.g., a small molecule, a peptide, an oligonucleotide, a protein) to activate intracellular signaling through the intracellular signaling domain. The activator can be any of the embodiments described herein, e.g., in Section II below. The activator binding domain can be any protein, protein fragment, or peptide capable of selectively binding the activator. In some embodiments, for example, the activator binding domain may include an antibody (e.g., a monoclonal antibody), an antibody fragment, a single chain variable fragment (scFv), a nanobody, or a peptide. In some embodiments, an activator binding domain may include a fragment of an antibody (e.g., a variable fragment) that binds to a selected activator. Antibodies, antibody fragments, scFvs, and nanobodies may be produced using various methods known in the art to target a specific activator. In some embodiments, the activator binding domain is an scFv, a heavy chain variable domain (VH), or a light chain variable domain (VL) of an antibody, or a VHH antibody that recognizes any of the activators described herein. For example, the activator binding domain can be an scFv, a VH, or a VLof an anti-FITC antibody (e.g., a 4M5.3 anti-FITC antibody). As another example, the activator binding domain can be an scFv, a VH, or a VLof an anti-DOTA antibody (e.g., a C8.2.5 anti-DOTA antibody). In a further example, the activator binding domain can be an scFv, a VH, or a VLof an anti-MPOB antibody. In some embodiments, the activator binding domain may be synthetic (e.g., engineered de novo to bind an activator). In some embodiments, an activator binding domain may be humanized to reduce immunogenicity and prevent an immune reaction to the CCR when administered to a subject (e.g., a human subject). Commercially available small molecule binding domains may be suitable for use as an activator binding domain in a CCR. The activator binding domain may have a molecular weight of from about 1 kDa to about 150 kDa, from about 1 kDa to about 100 kDa, from about 1 kDa to about 90 kDa, Fortem Ref. No. DCT.010WO from about 1 kDa to about 80 kDa, from about 1 kDa to about 70 kDa, from about 1 kDa to about 60 kDa, from about 1 kDa to about 50 kDa, from about 1 kDa to about 40 kDa, from about 1 kDa to about 35 kDa, from about 1 kDa to about 30 kDa, from about 1 kDa to about 25 kDa, from about 1 kDa to about 10 kDa, from about 5 kDa to about 150 kDa, from about 5 kDa to about 100 kDa, from about 5 kDa to about 90 kDa, from about 5 kDa to about 80 kDa, from about 5 kDa to about 70 kDa, from about 5 kDa to about 60 kDa, from about 5 kDa to about 50 kDa, from about 5 kDa to about 40 kDa, from about 5 kDa to about 35 kDa, from about 5 kDa to about 30 kDa, from about 5 kDa to about 25 kDa, from about 5 kDa to about 10 kDa, from about 10 kDa to about 150 kDa, from about 10 kDa to about 100 kDa, from about 10 kDa to about 90 kDa, from about 10 kDa to about 80 kDa, from about 10 kDa to about 70 kDa, from about 10 kDa to about 60 kDa, from about 10 kDa to about 50 kDa, from about 10 kDa to about 40 kDa, from about 10 kDa to about 35 kDa, from about 10 kDa to about 30 kDa, from about 10 kDa to about 25 kDa, from about 20 kDa to about 150 kDa, from about 20 kDa to about 100 kDa, from about 20 kDa to about 90 kDa, from about 20 kDa to about 80 kDa, from about 20 kDa to about 70 kDa, from about 20 kDa to about 60 kDa, from about 20 kDa to about 50 kDa, from about 20 kDa to about 40 kDa, from about 20 kDa to about 35 kDa, or from about 20 kDa to about 30 kDa. For example, the activator binding domain may include an scFv having a molecular weight of about 20 kDa to about 35 kDa. The activator binding domain may include a peptide having a molecular weight of about 1 kDa to about 10 kDa. Examples of activator binding domains that may be used in a CCR and corresponding activators are provided in Table 2. Table 2: Activator Binding Domains Activator SEQ ID NO Sequence Activator Binding Domain anti- SEQ ID NO: 9 DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLR Fluorescein fluorescein WYLQKPGQSPKVLIYKVSNRVSGVPDRFSGSGSGTDFTL or scFv KINRVEAEDLGVYFCSQSTHVPWTFGGGTKLEIKSSADD fluorescein AKKDAAKKDDAKKDDAKKDGGVKLDETGGGLVQPGG derivatives AMKLSCVTSGFTFGHYWMNWVRQSPEKGLEWVAQFRN (e.g., FITC) KPYNYETYYSDSVKGRFTISRDDSKSSVYLQMNNLRVED TGIYYCTGASYGMEYLGQGTSVTVS In some embodiments, a CCR may include an activator binding domain having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% Fortem Ref. No. DCT.010WO sequence identity to SEQ ID NO: 9. In some embodiments, the CCR may include an activator binding domain of SEQ ID NO: 9. In embodiments where the CCR is expressed in a Treg that also expresses an indirect CAR (e.g., as described in Section I.B below), the activator recognized by the CCR may be the same as the activator recognized by the indirect CAR (e.g., the antigen binding domain of the indirect CAR can be the same as the activator binding domain of the CCR). In such embodiments, the indirect CAR may recognize the same epitope on the activator as the CCR, or may recognize a different epitope on the activator than the CCR. Alternatively, the activator recognized by the indirect CAR can be different from the activator recognized by the CCR (e.g., the antigen binding domain of the CAR can be different than the activator binding domain of the CCR). In some embodiments, the antigen binding domain of the indirect CAR binds to a first small molecule, and the activator binding domain of the CCR binds to a second small molecule, where the first small molecule may be the same as or different than the second small molecule. In some embodiments, the antigen binding domain of the indirect CAR binds to a first epitope on a small molecule, and the activator binding domain of the CCR binds to a second epitope on the small molecule, where the first epitope may be the same as or different than the second epitope. 2. Intracellular Domain A CCR of the present technology may include an intracellular domain (also referred to herein as an “intracellular signaling domain”). The intracellular signaling domain may be positioned in an intracellular region of the CCR and may be designed to activate intracellular signaling upon binding of an activator to an extracellular activator binding domain. Optionally, the intracellular signaling domain may exhibit activity independent of binding of the activator to the activator binding domain (activator-independent activity), as described elsewhere herein. The intracellular signaling domain may activate a cytokine signaling pathway, such as a STAT5 pathway and / or other pathway that is downstream of an IL2 receptor. In some embodiments, activation of the cytokine signaling pathway may promote maintenance of a Treg phenotype, improvement of Treg survivability and / or proliferation, and / or upregulation of immunosuppression activity. Alternatively or in combination, activation of the cytokine signaling pathway may promote conversion of the Treg to a Treg memory phenotype (e.g., a central memory phenotype, a stem cell memory phenotype, an effector memory phenotype, or an effector memory re-expressing CD45RA phenotype). Fortem Ref. No. DCT.010WO An intracellular signaling domain may be derived from an endogenous cytokine receptor, such as an IL2 receptor or a TGFβ receptor. For example, an intracellular signaling domain may be derived from an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ), a TGFβ receptor I subunit, or a TGFβ receptor II subunit. In some embodiments, the intracellular signaling domain may include an intracellular domain, a fragment of an intracellular domain, or a variant of an intracellular domain of an endogenous cytokine receptor. For example, the intracellular signaling domain may include an intracellular domain, a fragment of an intracellular domain, or a variant of an intracellular domain of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ), a TGFβ receptor I subunit, or a TGFβ receptor II subunit. The intracellular domain, fragment of the intracellular domain, or variant of the intracellular domain may be capable of activating the cytokine signaling pathway activated by the endogenous cytokine receptor from which it was derived. In some embodiments, an intracellular signaling domain may include a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to an intracellular domain of an endogenous cytokine receptor (e.g., an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ)), a TGFβ receptor I subunit, or a TGFβ receptor II subunit. Examples of intracellular signaling domains that may be used in a CCR are provided in Table 3. Table 3: Intracellular Signaling Domains Receptor SEQ ID NO SequenceIL2RαSEQ ID NO: 10 TWQRRQRKSRRTIIL2RβSEQ ID NO: 11 NCRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGDVQKWLSSPFPSSSFSPGGLAPEISPLEVLERDKVTQLLLQQDKVPEPASLSSNHSLTSCFTNQGYF FFHLPDALEIEACQVYFTYDPYSEEDPDEGVAGAPTGSSPQPLQPLSGED DAYCTFPSRDDLLLFSPSLLGGPSPPSTAPGGSGAGEERMPPSLQERVPR DWDPQPLGPPTPGVPDLVDFQPPPELVLREAGEEVPDAGPREGVSFPWS RPPGQGEFRALNARLPLNTDAYLSLQELQGQDPTHLVIL2RγSEQ ID NO: 12 ERTMPRIPTLKNLEDLVTEYHGNFSAWSGVSKGLAESLQPDYSERLCLVSEIPPKGGALGEGPGASPCNQHSPYWAPPCYTLKPET Fortem Ref. No. DCT.010WO In some embodiments, a CCR may include an intracellular signaling domain having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 10 – SEQ ID NO: 12. In some embodiments, the CCR may include an intracellular signaling domain of any one of SEQ ID NO: 10 – SEQ ID NO: 12. In some embodiments, a CCR includes a single intracellular signaling domain. Alternatively, a CCR can include a plurality of intracellular signaling domains in tandem (e.g., two, three, four, five, or more intracellular domains in tandem). In such embodiments, some or all of the intracellular signaling domains may be the same intracellular signaling domain, or some or all of the intracellular signaling domains may be different intracellular signaling domains. 3. Transmembrane Domain A CCR of the present technology may include a transmembrane domain. The transmembrane domain may connect an intracellular portion and an extracellular portion of the CCR and may be designed to span a cell membrane and transduce a signal from an activator binding domain to an intracellular signaling domain upon binding of an activator to the activator binding domain. A transmembrane domain may be derived from an endogenous cytokine receptor, such as an IL2 receptor. For example, a transmembrane domain may be derived from an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ). In some embodiments, the transmembrane domain may include a transmembrane domain, a fragment of a transmembrane domain, or a variant of a transmembrane domain of an endogenous cytokine receptor. For example, the transmembrane domain may include a transmembrane domain, a fragment of a transmembrane domain, or a variant of a transmembrane domain of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ). The transmembrane domain, fragment of the transmembrane domain, or variant of the transmembrane domain may be capable of activating the cytokine signaling pathway activated by the endogenous cytokine receptor from which it was derived. Fortem Ref. No. DCT.010WO In some embodiments, a transmembrane domain may include a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to a transmembrane domain of an endogenous cytokine receptor (e.g., an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ)). Examples of transmembrane domains that may be used in a CCR are provided in Table 4. Table 4: Transmembrane Domains Receptor SEQ ID NO Sequence IL2Rα SEQ ID NO: 13 VAVAGCVFLLISVLLLSGL IL2Rβ SEQ ID NO: 14 IPWLGHLLVGLSGAFGFIILVYLLI IL2Rγ SEQ ID NO: 15 VVISVGSMGLIISLLCVYFWL In some embodiments, a CCR may include a transmembrane domain having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 13 – SEQ ID NO: 15. In some embodiments, the CCR may include a transmembrane domain of any one of SEQ ID NO: 13 – SEQ ID NO: 15. 4. Signal Peptide A CCR of the present disclosure may include a signal peptide. The signal peptide may be positioned at the N-terminus of the CCR and may be designed to direct expression of the CCR to the endoplasmic reticulum (ER). The CCR may be synthesized in the ER membrane and may be trafficked to the plasma membrane as a transmembrane protein. A signal peptide may be derived from an endogenous cytokine receptor or another type of receptor. For example, signal peptide may be derived from an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ), an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, Fortem Ref. No. DCT.010WO a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), a CD130, an immunoglobulin (e.g., an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA, an IgD, an IgE), a CD8, a CD28, or a GM- CSF. In some embodiments, a signal peptide may include the signal peptide portion of an endogenous cytokine receptor or another receptor. For example, the signal peptide may include the signal peptide portion of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ), an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), a CD130, an immunoglobulin, a CD8, a CD28, or a GM-CSF. In some embodiments, the signal peptide may include a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to a signal peptide of an endogenous cytokine receptor or another receptor (e.g., an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), an interleukin 2 receptor subunit γ (IL2Rγ), an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), an immunoglobulin, a CD8, a CD28, or a CD130). Fortem Ref. No. DCT.010WO In some embodiments, the signal peptide may be a signal peptide from any transmembrane or membrane-bound protein. The signal peptide may be sufficient to direct expression of the CCR to the ER. Examples of signal peptides that may be used in a CCR are provided in Table 5. Table 5: Signal Peptides Receptor SEQ ID NO Sequence IL2Rα SEQ ID NO: 16 MDSYLLMWGLLTFIMVPGCQA IL2Rβ SEQ ID NO: 17 MAAPALSWRLPLLILLLPLATSWASA IL2Rγ SEQ ID NO: 18 MLKPSLPFTSLLFLQLPLLGVG IL7Rα SEQ ID NO: 19 MTILGTTFGMVFSLLQVVSG IL15Rα SEQ ID NO: 20 MAPRRARGCRTLGLPALLLLLLLRPPATRG IL21Rα SEQ ID NO: 21 MPRGWAAPLLLLLLQGGWG In some embodiments, a CCR may include a signal peptide having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 16 – SEQ ID NO: 21. In some embodiments, the CCR may include a signal peptide of any one of SEQ ID NO: 16 – SEQ ID NO: 21. 5. Hinge A CCR of the present technology may comprise a hinge (also referred to herein as a “hinge domain”). The hinge may be positioned between the activator binding domain and the transmembrane domain and may be designed to increase the flexibility of the CCR. Increased flexibility may reduce spatial constraints between the activator binding domain and the activator (e.g., a small molecule activator adhered to a surface), facilitating access to the activator. In some embodiments, the hinge may be engineered to provide a desired distance between the plasma membrane of a cell expressing the CCR and an activator bound to the CCR. In some embodiments, the hinge may be a synthetic peptide designed to provide a desired length, flexibility, or both. In some embodiments, the hinge may be derived from an endogenous transmembrane protein. For example, the hinge may be derived from a CD8 (e.g., a CD8α), a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an inducible T cell costimulatory (ICOS), a CD27, an immunoglobulin (e.g., an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA, an IgD, an IgE), or an EpoR. In some embodiments, the hinge may include a hinge of an Fortem Ref. No. DCT.010WO endogenous transmembrane protein. For example, the hinge may be derived from a hinge of a CD8 (e.g., a CD8α), a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an ICOS, a CD27, an immunoglobulin, or an EpoR. In some embodiments, the signal peptide may include a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to a hinge of an endogenous transmembrane protein (e.g., a CD8 (e.g., a CD8α), a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an ICOS, a CD27, an immunoglobulin, or an EpoR). Examples of hinges that may be used in a CCR are provided in Table 6. Table 6: Hinges Hinge SEQ ID NO Sequence CD8α Hinge SEQ ID NO: 22 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD In some embodiments, a CCR may include a hinge having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to SEQ ID NO: 22. In some embodiments, the CCR may include a hinge of SEQ ID NO: 22. As described herein, the length of the hinge may affect whether the CCR exhibits activator-independent activity. For example, the hinge can be no more than 50 amino acids, 45 amino acids, 40 amino acids, 30 amino acids, 25 amino acids, 20 amino acids, 15 amino acids, 10 amino acids, 9 amino acids, 8 amino acids, 7 amino acids, 6 amino acids, 5 amino acids, 4 amino acids, 3 amino acids, 2 amino acids, or 1 amino acid in length. Alternatively or in combination, the hinge can be at least 1 amino acid, 2 amino acids, 3 amino acids, 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, 10 amino acids, 15 amino acids, 20 amino acids, 25 amino acids, 30 amino acids, 35 amino acids, 40 amino acids, 45 amino acids, or 50 amino acids in length. 6. Additional Components In some embodiments, a CCR of the present technology may include or be co- expressed with one or more additional components. Additional components that may be included in or co-expressed with a CCR are provided in Table 7. Fortem Ref. No. DCT.010WO Table 7: Additional Components Component SEQ ID NO Sequence Truncated SEQ ID NO: 23 MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSD CD19 GPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQ QMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGG LGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLP PRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVH PKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYY CHRGNLTMSFHLEITARPVLWHWLLRTGGWKVSAVTLAYLIFC LCSLVGILHLQRALVLRRKRKRMTDPTRRF P2A peptide SEQ ID NO: 24 GSGATNFSLLKQAGDVEENPGP T2A peptide SEQ ID NO: 25 GSGEGRGSLLTCGDVEENPGP E2A peptide SEQ ID NO: 26 GSGQCTNYALLKLAGDVESNPGP F2A peptide SEQ ID NO: 27 GSGVKQTLNFDLLKLAGDVESNPGP In some embodiments, a CCR may include or be co-expressed with a marker domain. The marker domain may be co-expressed with the cytokine receptor chain(s) of the CCR for purposes of identifying immune cells that are expressing the CCR (“positive cells”), enriching and purifying positive cells, acting as a conditional suicide switch for positive cells, and / or other relevant functions. The marker domain can be truncated (e.g., in the intracellular domain) such that the expressed truncated marker does not have the biological function of the native marker. The marker domain can be any cell surface molecule that is not present on natural T-cells. For example, a CCR may include a CD19 domain (e.g., a truncated CD19 domain of SEQ ID NO: 23), a CD20 domain (e.g., a truncated CD20 domain), a CD22 domain (e.g., a truncated CD22 domain), a CD34 domain (e.g., a truncated CD34 domain), or an EGFR domain (e.g., a truncated EGFR domain). In some embodiments, a CCR may include a marker domain having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to SEQ ID NO: 23. In some embodiments, the CCR may include a marker domain of SEQ ID NO: 23. Alternatively or in combination, the marker domain can be a detection marker, such as a fluorescent protein. For example, a CCR may include EBFP, Sapphire, T-Sapphire, ECFP, mCFP, Cerulean, CyPet, AmCyan1, Midori-Ishi Cyan, mTFP1, GFP, EGFP, AcGFP, TurboGFP, Emerald, Azami Green, ZsGreen, EYFP, Topaz, Venus, mCitrine, yPet, PhiYFP, ZsYellow1, mBanana, Kusabira Orange, mOrange, dTomato, tdTomato, DsRed, DsRed2, DsRed-Express, DsRed-Monomer, mTangerine, mStrawberry, AsRed2, mRFP1, JREd, mCherry, HcRed1, mRaspberry, HcRed-Tandem, mPlum, or AQ143. Fortem Ref. No. DCT.010WO In some embodiments, a construct for expression of a CCR may include a cleavage sequence, such as a 2A self-cleaving peptide sequence (e.g., a P2A peptide of SEQ ID NO: 24, a T2A peptide of SEQ ID NO: 25, a E2A peptide of SEQ ID NO: 26, or a F2A peptide of SEQ ID NO: 27). A 2A self-cleaving peptide sequence (also known as a “2A peptide”) may be included to link a CCR to one or more additional CCRs for co-expression. In some embodiments, a 2A peptide may link a first CCR to a second CCR. For example, a 2A peptide (e.g., of any one of SEQ ID NO: 24 – SEQ ID NO: 27) may link a first cytokine receptor chain (e.g., an IL2Rβ cytokine receptor chain or an IL2Rγ cytokine receptor chain) to a second cytokine receptor chain (e.g., an IL2Rβ cytokine receptor chain or an IL2Rγ cytokine receptor chain) to form a single protein that encompasses both chains of an engineered dual-chain CCR (e.g., a dual-chain CCR of SEQ ID NO: 4). After expression, the protein can be cleaved at the cleavage sequence to produce the separate two cytokine receptor chains of the dual-chain CCR. As another example, a 2A peptide (e.g., of any one of SEQ ID NO: 24 – SEQ ID NO: 27) may be included to link a cytokine receptor chain to a marker domain (e.g., the marker domain of SEQ ID NO: 23) to form a single protein that encompasses the cytokine receptor chain and the marker domain. After expression, the protein can be cleaved at the cleavage sequence to separate the cytokine receptor chain from the marker domain. In some embodiments, a construct for expression of a CCR may include a cleavage sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to SEQ ID NO: 24 – SEQ ID NO: 27. In some embodiments, the construct for expression of the CCR may include a cleavage sequence of SEQ ID NO: 24 – SEQ ID NO: 27. Alternatively or in combination, a construct for expression of a CCR may include an internal ribosome entry site (IRES) to allow for co-expression of an CCR with an additional CCR and / or to a marker domain. In some embodiments, an IRES may link a first CCR to a second CCR in an expression construct, such that the first CCR and the second CCR are translated as separate proteins. In some embodiments, an IRES may link a CCR to a marker domain, such that the CCR and the marker domain are translated as separate proteins. Fortem Ref. No. DCT.010WO B. Chimeric Antigen Receptors (CARs) In some embodiments, a Treg of the present technology includes a CAR (a “CAR Treg”). A CAR may include an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain of the CAR may include an antigen binding domain that binds specifically to an antigen. The antigen binding domain can be any protein, protein fragment, or peptide capable of selectively binding the antigen. In some embodiments, for example, the antigen binding domain may be or include an antibody (e.g., a monoclonal antibody), an antibody fragment, an scFv, a nanobody, or a peptide. In some embodiments, an antigen binding domain may be or include a fragment of an antibody (e.g., a variable fragment) that binds to a selected antigen. Antibodies, antibody fragments, scFvs, and nanobodies may be produced using various methods known in the art to target a specific antigen. In some embodiments, the antigen binding domain may be a VHH antibody, an scFv, a VH, a VL, or a ligand specific for a target antigen. The antigen binding domain of the CAR may bind to a specific epitope of the target antigen. In some embodiments, the CAR is a “direct CAR” having an antigen binding domain that recognizes an antigen expressed by a target cell. A direct CAR may be targeted to a target cell via direct binding of the antigen binding domain to the antigen expressed by the target cell. In some embodiments, the antigen recognized by a direct CAR is an autoantigen or an antigen expressed by an autoreactive inflammatory immune cell. In some embodiments, the CAR may be selected to target an antigen associated with an autoimmune and / or inflammatory disease (e.g., an autoimmune and / or inflammatory disease of the nervous system, joint, eye, skin, etc.). In some embodiments, the CAR may be selected to target an antigen associated with a transplanted organ or tissue. Examples of antigens that may be targeted by a CAR include carcinoembryonic antigen (CEA), CD19, CD83, citrullinated proteins (e.g., citrullinated vimentin), carbamylated proteins, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), and type II collagen. In some embodiments, the CAR is an “indirect CAR” having an antigen binding domain that recognizes an antigen that is not expressed by the target cell of the CAR. For instance, the antigen may be a “synthetic antigen” that is not expressed by normal cells or diseased cells of the subject. An indirect CAR may be targeted to a target cell via an immune- activating agent including (1) an activator that serves as the synthetic antigen and (2) a targeting moiety that binds to an antigen expressed by the target cell (e.g., an autoantigen or antigen Fortem Ref. No. DCT.010WO expressed by an autoreactive inflammatory immune cell). The indirect CAR may bind indirectly to the target cell by binding of the antigen binding domain to the activator of the immune-activating agent, and by binding of the targeting moiety of the immune-activating agents to the antigen expressed by the target cell. The activator and targeting moiety can be any of the embodiments described herein, e.g., in Section II below. In some embodiments, the antigen binding domain of an indirect CAR is a VHH antibody, an scFv, a VH, or a VLof an antibody, or a ligand that recognizes any of the activators described herein. For example, the antigen binding domain can be a VHH antibody, an scFv, a VH, or a VLof an anti-FITC antibody (e.g., a 4M5.3 anti-FITC antibody). As another example, the antigen binding domain can be a VHH antibody, an scFv, a VH, or a VLof an anti-DOTA antibody (e.g., a C8.2.5 anti-DOTA antibody). In a further example, the antigen binding domain can be a VHH antibody, an scFv, a VH, or a VL of an anti-MPOB antibody. In some embodiments, the antigen binding domain of an indirect CAR may be synthetic (e.g., engineered de novo to bind an activator). In some embodiments, the antigen binding domain may be humanized to reduce immunogenicity and prevent an immune reaction to the indirect CAR when administered to a subject (e.g., a human subject). Commercially available small molecule binding domains may be suitable for use as an antigen binding domain in an indirect CAR. The transmembrane domain of the CAR (e.g., a direct CAR or an indirect CAR) may link the extracellular domain to the intracellular domain. In some embodiments, the transmembrane domain may be a transmembrane domain derived from any transmembrane protein. The transmembrane domain may include a transmembrane region of a T-cell receptor (TCR) α chain, TCR β chain, TCR ζ chain, CD28, CD3ε, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, or CD154. For example, the transmembrane domain may include a CD8 transmembrane domain, including a CD8α hinge domain and / or a CD8α transmembrane domain. In some embodiments, the transmembrane domain may be synthetic. For example, a synthetic transmembrane domain may include mostly hydrophobic residues (e.g., glycine, leucine, isoleucine, alanine, valine, proline, methionine, phenylalanine, and tryptophan). In some embodiments, a first peptide linker (e.g., including glycine, serine, or combinations thereof) may connect the transmembrane domain to the extracellular domain. In some embodiments, a second peptide linker (e.g., including glycine, serine, or combinations thereof) may connect the transmembrane domain to the intracellular domain. Fortem Ref. No. DCT.010WO The intracellular domain of the CAR (e.g., a direct CAR or an indirect CAR), also referred to as the cytoplasmic domain, may be capable of activating a specialized immune cell function (e.g., an immune response). For example, the specialized immune cell function of a Treg may include cytolytic activity, cytokine secretion, or both. In some embodiments, the intracellular domain of the CAR may include the intracellular domain of TCR ζ chain, FcRγ, FcRβ, CD3ζ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b, or CD66d. In some embodiments, the intracellular domain of the CAR may include a portion of the intracellular domain of TCR ζ chain, FcRγ, FcRβ, CD3ζ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b, or CD66d sufficient to activate the specialized immune cell function. In some embodiments, the intracellular domain of the CAR includes one or more co-stimulatory domains, such as CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, HVEM (LIGHTR), lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, or B7-H3. In some embodiments, the intracellular domain of the CAR may include a 4-1BB signaling domain, a CD28 signaling domain, and / or a CD3ζ signaling domain. Binding of the antigen to the antigen binding domain of the CAR may initiate signal transduction through the transmembrane domain to the intracellular domain to activate the Treg. For example, binding of the antigen binding domain to an autoantigen may activate the Treg to elicit immune tolerance to the target cell expressing the autoantigen via bystander suppression, secretion of immunosuppressive cytokines, etc. As another example, binding of the antigen binding domain to an antigen on autoreactive inflammatory immune cells (e.g., IL23R) can allow the Treg to suppress immune cell activation against autoantigens by direct interaction mechanism (e.g., CTLA-4, LAG3). Examples of polynucleotide sequences for CARs are provided in Table 3. Table 8: CARs CAR SEQ ID NO Sequence anti-DOTA SEQ ID NO: 28 ATGGCTCTGCCAGTGACAGCTCTGCTGCTTCCTCTGGCTCTCC CAR TGCTGCATGCCGCTAGACCTGAGCAGAAACTCATCTCTGAAG AGGATCTGCACGTGAAACTGCAAGAGTCTGGCCCCGGACTG GTGCAGCCTTCTCAGTCTCTCTCTCTGACCTGTACCGTGTCCG GCTTCAGCCTGACCGATTATGGCGTGCACTGGGTTCGACAAT CCCCAGGCAAAGGACTCGAGTGGCTGGGAGTGATTTGGAGC GGCGGAGGCACAGCCTATAACACAGCCCTGATCAGCAGACT GAACATCTACCGGGACAACTCCAAGAACCAGGTTTTCCTGGA AATGAACTCCCTGCAGGCAGAGGACACCGCCATGTACTACT GCGCCAGAAGAGGCAGCTACCCCTACAATTACTTCGACGCCT GGGGCTGTGGCACAACCGTGACAGTTTCTAGTGGCGGAGGC GGATCTGGTGGTGGTGGTAGCGGTGGCGGAGGATCTCAGGC CGTGGTTATTCAAGAAAGCGCCCTGACAACCCCTCCTGGCGA GACAGTGACACTGACATGTGGCAGCTCTACAGGCGCCGTGA Fortem Ref. No. DCT.010WO CAR SEQ ID NO Sequence CCGCCAGCAATTACGCCAATTGGGTGCAAGAGAAGCCCGAC CACTGCTTCACAGGCCTGATCGGCGGCCACAACAATAGACCT CCAGGCGTGCCAGCTAGATTCAGCGGATCCCTGATCGGAGA CAAGGCCGCTCTGACAATCGCCGGCACACAGACAGAGGACG AGGCCATCTACTTTTGCGCCCTGTGGTACAGCGACCACTGGG TTATCGGCGGAGGAACCAGACTGACAGTGCTGGGCACAACA ACACCCGCACCTAGACCACCAACTCCAGCACCAACAATCGC CTCTCAACCCCTGAGTCTGAGGCCAGAGGCATGCAGACCAG CCGCTGGCGGTGCAGTTCACACTAGAGGACTGGACTTTGCCT GTGACATCTACATCTGGGCCCCTCTGGCTGGAACATGTGGTG TCCTGCTGCTGTCCCTGGTCATCACCCTGTACTGCAAGCGGG GCAGAAAGAAACTGCTGTACATCTTCAAGCAGCCCTTCATGC GGCCCGTGCAGACCACACAAGAGGAAGATGGCTGCTCCTGC AGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAGCTGAGAGT GAAGTTCTCCAGATCTGCCGACGCTCCCGCCTATCAGCAGGG ACAGAACCAGCTGTACAACGAGCTGAACCTGGGGAGAAGAG AAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGAGATCCT GAGATGGGCGGAAAGCCCCAGCGGAGAAAGAATCCTCAAGA GGGCCTGTATAATGAGCTGCAAAAGGACAAGATGGCCGAGG CCTACAGCGAGATCGGAATGAAGGGCGAGCGCAGAAGAGG AAAGGGACACGACGGACTGTACCAGGGCCTGAGCACAGCCA CCAAGGATACCTATGACGCCCTGCACATGCAGGCCCTGCCTC CAAGATGATGA anti- SEQ ID NO: 29 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGC fluorescein TTCTGCATGCCGCCAGACCTGACGTGGTCATGACACAGACAC CAR (second CTCTGAGCCTGCCTGTGTCTCTGGGAGATCAGGCCAGCATCA generation) GCTGCAGATCTAGCCAGAGCCTGGTGCACAGCAACGGCAAC ACCTACCTGCGGTGGTATCTGCAGAAGCCCGGCCAGTCTCCT AAGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGT GCCCGATAGATTTTCTGGCAGCGGCTCTGGCACCGACTTCAC CCTGAAGATCAATAGAGTGGAAGCCGAGGACCTGGGCGTGT ACTTCTGTAGCCAGTCTACCCACGTGCCATGGACCTTTGGCG GCGGAACAAAGCTGGAAATCAAGAGCAGCGCCGACGACGCC AAGAAGGACGCCGCTAAGAAGGATGACGCCAAAAAAGACG ATGCCAAAAAGGATGGCGGCGTGAAGCTGGACGAAACAGGC GGAGGACTTGTTCAGCCTGGCGGAGCCATGAAGCTGAGCTG TGTGACCAGCGGCTTCACCTTCGGCCACTACTGGATGAACTG GGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGTCGCCC AGTTCAGAAACAAGCCCTACAACTACGAAACCTACTACAGC GACAGCGTGAAGGGCAGATTCACCATCAGCCGGGACGACAG CAAGTCCAGCGTGTACCTGCAGATGAACAACCTGCGCGTGG AAGATACCGGCATCTACTACTGTACCGGCGCCAGCTACGGCA TGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTACAA CAACCCCTGCTCCTCGGCCTCCTACACCAGCTCCTACAATTG CCAGCCAGCCACTGTCTCTGAGGCCCGAAGCTTGTAGACCTG CTGCAGGCGGAGCCGTGCATACAAGAGGACTGGATTTCGCC TGCGACTTCTGGGTGCTCGTGGTTGTTGGCGGAGTGCTGGCT TGTTACTCCCTGCTGGTTACCGTGGCCTTCATCATCTTTTGGG TCAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAG CCCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGG CTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCG AGCTGAGAGTGAAGTTCAGCAGATCCGCCGACGCTCCTGCCT ATCAGCAGGGACAGAACCAGCTGTACAACGAGCTGAACCTG GGGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAG GCAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAG AATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAA GATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGC GCAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTG Fortem Ref. No. DCT.010WO CAR SEQ ID NO Sequence AGCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCA GGCCCTGCCACCTAGATGATGA anti- SEQ ID NO: 30 ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGC fluorescein TTCTGCATGCCGCCAGACCTGACGTGGTCATGACACAGACAC CAR (third CTCTGAGCCTGCCTGTGTCTCTGGGAGATCAGGCCAGCATCA generation) GCTGCAGATCTAGCCAGAGCCTGGTGCACAGCAACGGCAAC ACCTACCTGCGGTGGTATCTGCAGAAGCCCGGCCAGTCTCCT AAGGTGCTGATCTACAAGGTGTCCAACAGAGTGTCCGGCGT GCCCGATAGATTTTCTGGCAGCGGCTCTGGCACCGACTTCAC CCTGAAGATCAATAGAGTGGAAGCCGAGGACCTGGGCGTGT ACTTCTGTAGCCAGTCTACCCACGTGCCATGGACCTTTGGCG GCGGAACAAAGCTGGAAATCAAGAGCAGCGCCGACGACGCC AAGAAGGACGCCGCTAAGAAGGATGACGCCAAAAAAGACG ATGCCAAAAAGGATGGCGGCGTGAAGCTGGACGAAACAGGC GGAGGACTTGTTCAGCCTGGCGGAGCCATGAAGCTGAGCTG TGTGACCAGCGGCTTCACCTTCGGCCACTACTGGATGAACTG GGTCCGACAGAGCCCTGAGAAAGGCCTGGAATGGGTCGCCC AGTTCAGAAACAAGCCCTACAACTACGAAACCTACTACAGC GACAGCGTGAAGGGCAGATTCACCATCAGCCGGGACGACAG CAAGTCCAGCGTGTACCTGCAGATGAACAACCTGCGCGTGG AAGATACCGGCATCTACTACTGTACCGGCGCCAGCTACGGCA TGGAATATCTCGGCCAGGGCACCAGCGTGACCGTGTCTACAA CAACCCCTGCTCCTCGGCCTCCTACACCAGCTCCTACAATTG CCAGCCAGCCACTGTCTCTGAGGCCCGAAGCTTGTAGACCTG CTGCAGGCGGAGCCGTGCATACAAGAGGACTGGATTTCGCC TGCGACTTCTGGGTGCTCGTGGTTGTTGGCGGAGTGCTGGCT TGTTACTCCCTGCTGGTTACCGTGGCCTTCATCATCTTTTGGG TCCGAAGCAAGCGGAGCCGGCTGCTGCACAGCGACTACATG AACATGACCCCTAGACGGCCCGGACCTACCAGAAAGCACTA CCAGCCTTACGCTCCTCCTAGAGACTTCGCCGCCTACAGATC CAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGC CCTTCATGCGGCCCGTGCAGACCACACAAGAGGAAGATGGC TGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGA GCTGAGAGTGAAGTTCAGCAGATCCGCCGACGCTCCTGCCTA TCAGCAGGGACAGAACCAGCTGTACAACGAGCTGAACCTGG GGAGAAGAGAAGAGTACGACGTGCTGGACAAGCGGAGAGG CAGAGATCCTGAGATGGGCGGAAAGCCCCAGCGGAGAAAGA ATCCTCAAGAGGGCCTGTATAATGAGCTGCAGAAAGACAAG ATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCG CAGAAGAGGCAAGGGACACGATGGACTGTACCAGGGCCTGA GCACCGCCACCAAGGATACCTATGATGCCCTGCACATGCAG GCCCTGCCACCTAGATGATGA In some embodiments, a CAR is encoded by a sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 87%, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or about 100% sequence identity to any one of SEQ ID NO: 28 – SEQ ID NO: 30. In some embodiments, the CAR is encoded by a sequence of any one of SEQ ID NO: 28 – SEQ ID NO: 30. Fortem Ref. No. DCT.010WO C. Vectors The present technology provides polynucleotides encoding one or more engineered receptors described herein (e.g., a CCR, a CAR, or both). A polynucleotide may include an RNA sequence or a DNA sequence encoding an engineered receptor, or an RNA sequence or a DNA sequence reverse complementary to a sequence encoding an engineered receptor. In some embodiments, the polynucleotide encoding the engineered receptor may be part of a polynucleotide construct (also referred to herein as a polynucleotide expression cassette) capable of expressing the engineered receptor in a cell (e.g., an immune cell). The polynucleotide expression cassette can be a plasmid, a cosmid, a viral vector, or a combination thereof. The polynucleotide expression cassette may include a promoter, an open reading frame (e.g., encoding the engineered receptor), a 3’ untranslated region, or combinations thereof. In some embodiments, the polynucleotide expression cassette may include two or more open reading frames. For example, the polynucleotide expression cassette may include a first open reading frame encoding a CCR and a second open reading frame encoding a CAR. The expression cassette may further include an origin of replication, a restriction endonuclease site, a selectable marker, or combinations thereof. The expression cassette may be capable of expressing a CCR, a CAR, or both in a cell (e.g., an immune cell). In some embodiments, the cell may be a mammalian cell (e.g., a human cell). For example, the cell may be a human T-cell. A polynucleotide or polynucleotide expression cassette may be obtained using recombinant methods known in the art. Alternatively or in addition, the polynucleotide or polynucleotide expression cassette may be generated synthetically. The polynucleotide expression cassette can also encode elements for gene editing, nucleases, reverse transcriptases, integrases, recombinases, and combinations thereof. As non-limiting examples, a nuclease encoded by the polynucleotide expression cassette can include a zinc finger nuclease, a transcription activator-like effector nuclease (TALEN), a Cas3 nuclease, a Cas9 nuclease, a CRISPR / Cas12 nuclease, a CRISPR / Cas14 nuclease, a Fok1 nuclease, or a combination thereof. The polynucleotide expression cassette can also encode additional transcripts and proteins which further affect cell phenotype, such as small interfering RNA (siRNA), microRNA (miRNA), short hairpin RNA (shRNA), ribozymes, transcription factors, or immunomodulatory elements. Fortem Ref. No. DCT.010WO In some embodiments, a polynucleotide expression cassette for expressing two or more proteins may include a cleavage sequence, such as a 2A self-cleaving peptide sequence (e.g., a P2A peptide, a T2A peptide, a E2A peptide, or a F2A peptide). For instance, a 2A peptide may be included to link a CCR to a CAR for co-expression. After expression, the protein can be cleaved at the cleavage sequence to separate the CCR from the CAR as separate proteins. at the cleavage sequence to separate the cytokine receptor chain from the marker domain. Alternatively or in combination, a polynucleotide expression cassette for expressing two or more proteins may include an IRES. For instance, an IRES may be included to link a CCR to a CAR for co-expression, such that the CCR and the CAR are translated as separate proteins. Also provided herein are vectors including the polynucleotide expression cassette. The vector may be capable of delivering the polynucleotide expression cassette to a target cell (e.g., an immune cell). Upon delivery, a protein encoded by the polynucleotide expression cassette (e.g., a CCR, a CAR, or combinations thereof) may be expressed in the cell. In some embodiments, the polynucleotide expression cassette is encoded within a viral vector. In some embodiments, the viral vector is a lentiviral vector, an adeno-associated viral vector, a vaccinia viral vector, a poxvirus viral vector, a herpes viral vector, an alphavirus viral vector, gamma retrovirus, a polyoma viral vector, or a combination thereof. In some embodiments, the viral vector is a gamma retrovirus, an adeno-associated viral vector or a lentiviral vector. In some embodiments, the viral vector is a lentiviral vector. In some embodiments, the viral vector has a titer of between about 106and about 109virions per ml. In some embodiments, transfection includes delivery of nonviral vectors (e.g., in a lipid or chitosan nanoparticles or with a colloidal dispersion system). A vector encoding an engineered receptor may be generated and delivered to an immune cell using standard cloning and gene delivery protocols, for example as described in Sambrook et al. (2001, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), which is herein incorporated by reference. A vector may encode a selectable marker, a reporter gene, or both to facilitate selection of cells (e.g., immune cells) successfully transfected and expressing a protein encoded by the expression cassette. Fortem Ref. No. DCT.010WO D. Methods for Manufacturing Immune Cells 1. Collection An immune cell to be engineered (e.g., to express a CCR, a CAR, or both) may be obtained from a subject. Immune cells may be obtained from blood (e.g., peripheral blood mononuclear cells), bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, tumors, or combinations thereof collected from the subject. Immune cells may be collected from a subject using any technique known in the art (e.g., Ficoll separation or apheresis). In some embodiments, immune cells collected from a subject may include T-cells, monocytes, granulocytes, B-cells, other nucleated white blood cells, red blood cells, platelets, or combinations thereof. In some embodiments, immune cells (e.g., T-cells, Tregs, B-cells, NK cells, macrophages, γδ T-cells, or combinations thereof) may be collected from a donor. The cells may be obtained from blood (e.g., peripheral blood mononuclear cells), bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, tumors, or combinations thereof collected from the subject. Immune cells (e.g., precursors to engineered immune cells of the present technology) may be collected from a subject using any technique known in the art (e.g., Ficoll separation). In some embodiments, the precursor cells are collected from blood, for example through apheresis, leukapheresis, or buffy coat preparation. In some embodiments, precursor cells (e.g., cells to be engineered to express a CCR, a CAR, or both) are immune cells collected from a donor. The immune cells can be of a single type, or can be a heterogeneous collection of cells. The immune cells can include T- cells, Tregs, B-cells, natural killer cells (NK cells), FcεRIγ deficient NK cells (g-NK cells), macrophages, monocytes, basophils, eosinophils, neutrophils, megakaryocytes, thrombocytes, or combinations thereof. The immune cells can be enriched for specific cell types. For many of the methods disclosed herein, blood-derived immune cells are separated from other whole blood components, for example through monocyte depletion, centrifugation, filtration, or clotting. The immune cells can also be subjected to positive or negative selection for certain cell types. In some embodiments, immune cells from a donor are separated from other peripheral blood mononuclear cells (PBMCs) through depletion of surface markers expressed by non-target cell populations, such as CD127 and / or CD8, and through positive selection for surface markers Fortem Ref. No. DCT.010WO expressed by a target cell population, such as CD3, CD4, and / or CD25. In specific cases, the immune cells are depleted of memory (e.g., central memory T cells, effector memory T cells, virtual memory T cells, memory B cells, etc.) and / or effector cells. In some embodiments, the immune cells are enriched for a particular type of T or B cell, such as Tregs. In some embodiments, after enrichment, the immune cells are at least 80%, 85%, 90%, 95%, 99%, or 99.9% Tregs. As a nonlimiting example, immune cell enrichment can include selectively binding one or more cell type-specific surface markers on a magnetically separatable bead or on a column. In some embodiments, the immune cells are of a single cell type. In some embodiments, the immune cells are obtained through leukapheresis, bone marrow biopsy, or a combination thereof. In some embodiments, the immune cells include at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% naïve T cells and naïve B cells as a percentage of total cell population, e.g., prior to contacting the immune cells with the activator. The precursor cells can also include a totipotent, pluripotent, multipotent, or oligopotent cell. In many such cases, the precursor cells include immune precursor cells, such as common myeloid progenitor cells, granulocyte progenitor cells, myeloblasts, monocytes, common lymphoid progenitor cells, lymphoid progenitor cells, progenitor B cells, or combinations thereof. In some embodiments, the precursor cells include a stem cell, such as a tetraploid reprogrammed cell, an induced pluripotent stem cell, an embryoblast, a lymphoid stem cell, or a myeloid stem cell. 2. Transfection The immune cells may be isolated and transfected with a polynucleotide expression cassette encoding one or more engineered receptors (e.g., a CCR and / or a CAR), thereby engineering the immune cell to express the engineered receptor(s). The polynucleotide expression cassette can be a plasmid, a cosmid, a viral vector, or a combination thereof. The polynucleotide expression cassette can be naked or delivered via a viral vector or a nonviral vector. A polynucleotide expression cassette may be introduced into a target cell using physical or chemical means. In some embodiments, a polynucleotide expression cassette may be introduced into a target cell using calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. In some embodiments, the polynucleotide expression cassette may be introduced using colloidal dispersion systems (e.g., Fortem Ref. No. DCT.010WO macromolecule complexes), nanocapsules, microspheres, beads, lipid-based systems (e.g., oil- in-water emulsions, micelles, mixed micelles, liposomes), and the like. Additional transfection methods are described in Sambrook et al. (2001, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, the immune cells are contacted to a receptor agonist concurrently with and / or prior to transfection. In some embodiments, the receptor agonist is selected from the group consisting of granulocyte macrophage-colony stimulating factor (GM- CSF), stem cell factor (SCF), interleukin 1 (IL1), interleukin 2 (IL2), interleukin -3 (IL3), a CD3 agonist, a CD4 agonist, a CD8 agonist, a CD16 agonist, a CD23 agonist, a CD28 agonist, a CD47 agonist, a CD80 agonist, a CD113 agonist, a CD131 agonist, a CD137 agonist, an HLA-E agonist, a 41BBL agonist, and a combination thereof. In some embodiments, the receptor agonist is selected from the group consisting of a CD3 agonist, a CD23 agonist, a CD28 agonist, an IL2 receptor agonist, and a combination thereof. In some embodiments, the CD3 agonist is an antigen. In some embodiments, the receptor agonist is coupled to a substrate. In some embodiments, the substrate includes a peptide, an antibody, a minibody, a nanobody, a fragment antigen-binding, a nanoparticle, a microparticle, a polymer matrix, a surface, a surface functionalization (e.g., a dextran polymer functionalized with the activator), a carbon nanomaterial, a quantum dot, a surface, or a combination thereof. In some embodiments, the substrate is contacted to the immune cells at a ratio of between about 50:1 and about 1:1 (substrate to immune cells). In some embodiments, the immune cells are contacted with a CD3 agonist and a CD28 agonist prior to transfection. In some embodiments, the immune cells are contacted with IL2 prior to transfection. In some embodiments, the immune cells are contacted with IL2 during transfection. In some embodiments, the immune cells are expanded by about 2-fold, about 5-fold, about 10-fold, about 25-fold, about 50-fold, or about 100-fold prior to transfection and the contacting to the substrate. In some embodiments, the immune cells are expanded by between about 2-fold and about 10-fold, by between about 2-fold and about 25- fold, by between about 5-fold and about 50-fold, or by between about 10-fold and about 100- fold prior to transfection and the contacting to the substrate. Following transfection, the immune cells can be fractionated on a substrate. In some embodiments, the immune cells are collected on a substrate that is functionalized with an activator (e.g., a species which binds to an activator binding domain of a CCR), which may also be used to perform ex vivo activation of the immune cells as described herein. Activator functionalized substrates (e.g., test tube surfaces, cell culture flasks, cell culture bags, cell Fortem Ref. No. DCT.010WO culture plates, G-rex bioreactors, CentriCult chambers, cassettes, column materials, beads such as magnetically separatable beads) can selectively bind cells which express engineered receptors. Alternatively, or in addition thereto, immune cells can be collected on substrates functionalized with agents which bind engineered (e.g., CCR) or native (e.g., phenotype- specific immune cell markers, such as CD45RA or CCR7) receptors. A method can include separating immune cells which express a particular engineered receptor from immune cells which do not express the receptor by binding the receptor to a substrate. Unbound cells can then be washed or removed, while the receptor-expressing immune cells can be collected from the substrate. Alternatively, the substrate (along with bound immune cells) can be separated from unbound immune cells, for example through gravimetric or magnetic separation. In some embodiments, immune cells are fractionated by cell phenotype. During such processes, subsets of the engineered immune cell population which express a particular cell marker (e.g., CCR7 or CD45RA) can be captured and separated from subsets of the engineered immune cell population which do not express the cell marker. For example, T-cells can be separated from non-T-cells of the immune cell population through CD3 affinity collection. In some embodiments, a method includes selecting memory T cells from an immune cell population, for example by collecting CCR7+ and / or CCR7+ / CD45RA+ cells from the immune cell population. 3. Activation Optionally, immune cells expressing a CCR may be activated ex vivo by contacting the cells with an activator. Activating the immune cells may promote maintenance of a desired phenotype, such as a Treg phenotype, and / or conversion to a desired phenotype, such as a Treg memory cell phenotype. As a result, an activated population of engineered immune cells may have a higher proportion of Treg phenotypes and / or Treg memory phenotypes (e.g., stem-cell memory phenotypes and central memory phenotypes) than a population of engineered immune cells that has not been activated. In some embodiments, activation is performed on engineered immune cells ex vivo prior to administration to a subject, e.g., by exposure to an activator bound to a substrate, such as a surface (e.g., a plate surface), a bead (e.g., a polystyrene paramagnetic bead), a carrier protein (e.g., an antibody), a carrier polymer (e.g., a synthetic polymer, a biopolymer), a carrier nucleic acid (e.g., an oligonucleotide, a polynucleotide), or combinations thereof. The immune cells can be exposed to the activator for at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 Fortem Ref. No. DCT.010WO hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, or 24 hours. Ex vivo activation may be performed at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, or 24 hours before administration of the engineered immune cells to the subject. The concentration of the activator for ex vivo activation can be within a range from 1 nM to 1000 nM, 1 nM to 500 nM, 1 nM to 100 nM, 1 nM to 50 nM, 1 nM to 10 nM, 10 nM to 1000 n, 10 nM to 500 nM, 10 nM to 100 nM, 10 nM to 50 nM, 50 nM to 1000 nM, 50 nM to 500 nM, 50 nM to 100 nM, 100 nM to 1000 nM, 100 nM to 500 nM, or 500 nM to 1000 nM. Following ex vivo activation, the substrate-bound activator may be removed from the immune cells, e.g., by cleaving the activator from the substrate (e.g., via disulfide reduction, pH-based cleavage, photocleavage, protease cleavage) and / or mechanical disruption. Additional details and examples of compositions and methods for immune cell activation that are applicable to the present technology are provided in International Application No. PCT / US2023 / 082604, the disclosure of which is incorporated by reference herein in its entirety. E. Compositions of Engineered Immune Cells Further provided herein are compositions including engineered immune cells (e.g., engineered Tregs) suitable for administration to a subject in need thereof. The engineered immune cells or precursor cells thereof may be cultured and formulated for delivery to a subject (e.g., a donor of precursors of the engineered immune cells). In some embodiments, precursor cells are cultured prior to transfection with a polynucleotide encoding an engineered receptor. In such cases, the precursor cells can be activated, differentiated, and / or expanded. The cells can be further cultured following transfection, for example, to further expand the cells or to affect terminal differentiation. In some embodiments, precursor cells are transfected with a CCR and / or a CAR prior to culturing, as described herein. An engineered immune cell composition can be formulated with a solution tolerated by the immune cells. The immune cells are formulated with a solution of biological origin, such as plasma; a synthetic solution, such as saline, Ringer’s solution, dextrose solution, phosphate buffered saline; water; or a combination thereof. The formulation can also include a nonaqueous vehicle, such as ethyl oleate or a fatty acid triglyceride. An engineered immune cell composition can include a pharmaceutically acceptable carrier, diluent, or excipient. In some embodiments, the composition includes a Fortem Ref. No. DCT.010WO viscosity-enhancing agent (e.g., sodium carboxymethylcellulose, dextran, or glycerol). In some embodiments, the composition includes an isotonicity imparting agent, such as sodium chloride, potassium chloride, or monosodium phosphate. In some embodiments, the composition includes a stabilizing agent, such as carboxymethyl cellulose, alginate, polyethylene glycol, or a polyol. In some embodiments, the composition includes a preservative, such as thimerosal, m- or o-cresol, formalin or benzyl alcohol. In some embodiments, the composition includes an adjuvant, such as aluminum hydroxide. In some embodiments, the composition includes a buffer, such as bicarbonate, TRIS, HEPES, MOPS, CHES, CHAPS, or phosphate buffered saline. Engineered immune cell compositions can either be liquid injectables or solids which can be taken up in a suitable liquid as a suspension or solution for injection. Thus, in a non-liquid formulation, the excipient can include, for example, dextrose, human serum albumin, and / or preservatives to which sterile water or saline can be added prior to administration. II. Activators An activator may activate an engineered Treg of the present technology by binding to an engineered receptor of the Treg, such as a CCR or an indirect CAR. The activator may be a small molecule, a peptide, an oligonucleotide, or a protein. In some embodiments, an activator may be selected to have low toxicity, low immunogenicity, low cross-reactivity, or combinations thereof to reduce unfavorable side effects when administered to a subject (e.g., a human subject). For instance, the activator can be a molecule that is non-toxic to humans, included in an Inactive Ingredients Database, or both. In some embodiments, the activator is an exogenous activator (e.g., an exogenous small molecule, an exogenous peptide, an exogenous oligonucleotide, or an exogenous protein) that is not naturally present in a target environment (e.g., a human subject) to prevent activation of the engineered receptor in the absence of an external stimulus (e.g., administration of the activator), prevent cross-reactivity of the activator with other biological components, and to enable dynamic control of receptor signaling. A small molecule activator can have a molecular weight less than or equal to 5 kDa, 4 kDa, 3 kDa, 2 kDa, 1 kDa, 500 Da, 200 Da, or 100 Da; and / or can have a molecular weight within a range from 50 Da to 500 Da, 100 Da to 500 Da, 100 Da to 1 kDa, 200 Da to 500 Da, 500 Da to 1 kDa, 1 kDa to 2 kDa, 1 kDa to 5 kDa, or 2 kDa to 5 kDa. Examples of Fortem Ref. No. DCT.010WO small molecule activators (e.g., haptens) that may be used to activate an engineered receptor include fluorophores (e.g., fluorescein, fluorescein derivatives, indocyanines, indocyanine derivatives, cyanines, cyanine derivatives), chelators (e.g., DOTA), or other small molecules. For example, the fluorescein derivative may be fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, or 6-FAM phosphoramidite. In some embodiments, the activator is selected from the group consisting of fluorescein, fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5- carboxamide, fluorescein-6-carboxamide, 6-FAM phosphoramidite, topiramate hemisuccinate, creatine, acetaminophen, ketamine, propofol, lidocaine, ractopamine, salicylate, salicylic acid, sulfasalazine, dapsone, albendazole, ivermectin, levamisole, permethrin, pyrantel, thiabendazole, procainamide, sulfamethazine, amikacin, amoxicillin, ampicillin, cefazolin, cefuroxime, cephalexin, chloramphenicol, chloramphenicol, ciprofloxacin, clenbuterol, cloxacillin, colistin A, dicloxacillin, enrofloxacin, furaltadone, gentamicin, gentamicin, kanamycin, kanamycin, kincomycin, lincomycin, metronidazole, nafcillin, nalidixic acid, neomycin, neomycin, nitrofurazone, norfloxacin, ofloxacin, oxacillin, spectinomycin, streptomycin, streptomycin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadimidine, sulfametoxydiazine, sulfanilamide, trimethoprim, carbamazepine, ethosuximide, lamotrigine, primidone, cetirizine, chlorpheniramine, diphenhydramine, doxylamine, promethazine, sulfadimethoxine, benzothiazinone, butylated hydroxytoluene, tripelennamine, chlorpromazine, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, ribavirin, meprobamate, acebutolol, atenolol, penbutolol, warfarin, salmeterol, aflatoxin B1, tetraxetan (DOTA), 4-[(6-methylpyrazin-2-yl) oxy]benzoate (MPOB), biotin, melamine, methotrexate, amphetamine, diethylpropion, dextromethorphan, pseudoephedrine, dihydrochlorothiazide, hydrochlorothiazide, clonazepam, diazepam, nitrazepam, rhodamine B, fluorescent brightener Ksn, zearalenone, Sudan Red1, acetaminophen, acrylamide, benzoic acid, benzophenone, benzothiazine, mercaptobenzothiazole, erythrosine, Sudan, tartrazine, erythromycin, sirolimus, atropine, ethyl glucuronide, aflatoxin M1, methocarbamol, fentanyl, hydromorphone, morphine, remifentanil, tapentadol, tramadol, pregabalin, gabapentin, amitriptyline, desipramine, imipramine, nortriptyline, venlafaxine, dinitrophenyl, His-tag, PEG methoxy group, etodolac, ibuprofen, ketoprofen, meclofenamic acid, phenylbutazone, acetyl salicylic acid, acetamiprid, acetochlor, carbadazim, carbaryl, chlorothalonil, chlorpyrifos, fenpropathrin, imazalil, imidacloprid, parathion, abscisic acid, dibutyl phthalate, clonazepam, Fortem Ref. No. DCT.010WO lorazepam, oxazepam, phenobarbital, secobarbital, zaleplon, zolpidem, trazodone, fluoxetine, fluvoxamine, cortisone, dexamethasone, dihydrotestosterone, fluocinolone, methylprednisolone, prednisolone, stanozolol, triamcinolone, mazindol, methamphetamine, methylphenidate, modafinil, chrysoidine, deoxynivalenol, fumonisin, microcystin Lr, ochratoxin, sterigmatocystin, T-2 toxin, sildenafil, tadalafil, scopolamine, florfenicol, pirlimycin, and sulfaquinoxaline. In some embodiments, an activator may be used to activate an engineered Treg expressing a CCR. For example, the activator may be used to promote maintenance of a desired phenotype (e.g., Treg phenotype), conversion to a desired phenotype (e.g., Treg memory phenotype), activation of cytokine signaling pathways (e.g., STAT5 signaling), upregulation of immunosuppressive markers and / or cytokines (e.g., IL10, IL35, TGFβ, CTLA-4, PD-1, LAG3, GARP, CD39), and / or improved cell proliferation and survival. Activation may be performed ex vivo (e.g., during immune cell manufacturing) or in vivo (e.g., during immune cell therapy treatment). In some embodiments, activation is performed both ex vivo and in vivo. In some embodiments, activation is performed ex vivo but not in vivo. In some embodiments, activation is performed in vivo but not ex vivo. In some embodiments, activation is not performed either ex vivo or in vivo, such that the CCR relies primarily or entirely on activator- independent activity for its effect. For ex vivo activation, the activator may be conjugated (e.g., via covalent or non-covalent linkages) or otherwise attached (e.g., adsorbed, adhered) to a substrate, such as a surface (e.g., a plate surface), a bead (e.g., a polystyrene paramagnetic bead), a carrier protein (e.g., an antibody), a carrier polymer (e.g., a synthetic polymer, a biopolymer), a carrier nucleic acid (e.g., an oligonucleotide, a polynucleotide), or combinations thereof. For example, the activator may be conjugated to a carrier protein by classical stochastic cysteine and lysine conjugations, or through a site-specific conjugation technology. In some embodiments, the activator may be adhered to a surface, and engineered Tregs expressing the CCR may be added to the surface to activate the Tregs. In some embodiments, the activator may be adsorbed to beads, and the beads may be added to a suspension of engineered Tregs to activate the Tregs. The beads may be removed prior to administration of the engineered Tregs to a subject. Additional examples of techniques for ex vivo activation are provided in International Patent Application No. PCT / US2023 / 082604, which is incorporated herein by reference in its entirety. For in vivo activation, the activator may be part of an immune-activating agent that is administered to the subject. An immune-activating agent can include an activator that Fortem Ref. No. DCT.010WO binds to an engineered immune cell and a targeting moiety that binds to a target for the immune cell (e.g., a cell for which immune tolerance is desirable). The targeting moiety can be a carrier protein, such as an antibody, an antibody fragment, a single chain variable fragment (scFv), a nanobody, or a peptide. In some embodiments, the targeting moiety (e.g., carrier protein) may be humanized to reduce immunogenicity. The activator can be conjugated (e.g., via covalent or non-covalent linkages) to the targeting moiety to form the immune-activating agent. For example, the activator may be conjugated to the targeting moiety (e.g., carrier protein) by classical stochastic cysteine and lysine conjugations, or through a site-specific conjugation technology. The immune-activating agent (e.g., activator-carrier protein conjugate) may be administered to a subject who has been or will be treated with engineered Tregs expressing the CCR. In some embodiments, the targeting moiety may be an antibody, antibody fragment, scFv, nanobody, peptide, etc., that binds to an antigen of interest, such as an autoantigen or an antigen expressed by an inflammatory immune cell. For example, the autoantigen may be carcinoembryonic antigen (CEA), CD19, CD83, citrullinated proteins (e.g., citrullinated vimentin), carbamylated proteins, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. For instance, examples of antibody fragments that target citrullinated proteins are described in U.S. Patent Application Publication No. 2023 / 0080155. As another example, the antigen expressed by the inflammatory immune cell can be IL23R or CD83. Targeting moieties such as antibodies, antibody fragments, scFvs, nanobodies, peptides, etc., that recognize an antigen of interest may be obtained from commercial sources or generated in accordance with techniques known to those of skill in the art. In some embodiments, the targeting moiety recognizes an antigen associated with an autoimmune and / or inflammatory disease of the nervous system (e.g., multiple sclerosis), such as myelin basic protein, myelin associated glycoprotein, myelin oligodendrocyte glycoprotein, proteolipid protein, oligodendrocyte myelin oligoprotein, myelin associated oligodendrocyte basic protein, oligodendrocyte specific protein, heat shock proteins, NOGO A, glycoprotein Po, peripheral myelin protein 22, or 2’3’-cyclic nucleotide 3’-phosphodiesterase. In some embodiments, the targeting moiety recognizes an antigen associated with an autoimmune and / or inflammatory disease of a joint (e.g., rheumatoid arthritis), such as Fortem Ref. No. DCT.010WO citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen, citrulline- substituted cyclic and linear filaggrin peptides, collagen peptides (e.g., type I, II, III, IV, or V), human cartilage glycoprotein 39 peptides, heat shock proteins, heterogeneous nuclear ribonucleoprotein (hnRNP) A2 peptides, hnRNP Bl, hnRNP D, Ro60 / 52, BiP, keratin, vimentin, fibrinogen, annexin V, glucose 6 phosphate isomerase, acetyl-calpastatin, pyruvate dehydrogenase, aldolase, topoisomerase I, snRNP, PARP, Scl-70, Scl-lOO, phospholipid antigens (e.g., anionic cardiolipin and phosphatidylserine, neutrally charged phosphatidylethanolamine and phosphatidylcholine), matrix metalloproteinase, fibrillin, or aggrecan. In some embodiments, the targeting moiety recognizes an antigen associated with an autoimmune and / or inflammatory disease of the eye, such as citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen, type II collagen, retinal arrestin, S- arrestin, interphotoreceptor retinoid-binding proteins, beta-crystallin B1, retinal proteins, or choroid proteins. In some embodiments, the targeting moiety recognizes a human heat shock protein (HSP) antigen, such as HSP60, HSP70, or HSP90. In some embodiments, the targeting moiety recognizes an antigen associated with an autoimmune and / or inflammatory disease of the skin, such as a keratinocyte antigen, an antigen present in the dermis or epidermis, a melanocyte antigen (e.g., melanin, tyrosinase), desmoglein (e.g., desmoglein 1 or 3), BP180, BP230, plectin, integrins (e.g., integrin α4β6), collagens (e.g., type VII collagen), laminins (e.g., laminin 332, laminin γ1), plakins (e.g., envoplakin, periplakin, desmoplakin), keratins (e.g., KRT5, KRT8, KRT15, KRT17, KRT31), keratin filament-associated proteins, filaggrin, comeodesmosin, or elastin. In some embodiments, the targeting moiety recognizes an antigen associated with rejection of a transplanted organ / tissue or graft versus host disease, such as the major histocompatibility complex (MHC) specific to the transplanted organ / tissue or to the host, β2- microglobulin, antigens from ABO system, antigens from rhesus system, isohemagglutinins, HLA-DR, HLA-B, HLA-A, minor histocompatibility antigens (e.g., HLA-E, HLA-F and HLA-G), HLAs corresponding to MHC class I (A, B, and C), HLAs corresponding to MHC class II (e.g., DP, DM, DOA, DOB, DQ, and DR), or HLAs corresponding to MHC class III (e.g., components of the complement system). In some embodiments, the antigen is an HLA- A2 cell surface protein. Fortem Ref. No. DCT.010WO Binding of the immune-activating agent to the antigen and to the CCR may recruit the engineered Treg to a target cell. In some embodiments, the immune cell is also engineered to express a CAR for an antigen of the target cell, which may or may not be the same as the antigen recognized by the immune-activating agent. Accordingly, binding of the immune-activating agent to its respective antigen may facilitate and / or enhance binding of the CAR to its respective antigen, which in turn may facilitate activation of the CAR and the immunomodulatory function of the Treg. In some embodiments, it may be important or even necessary for the activator to be attached to a surface to effectively activate Tregs expressing the CCR. For example, the use of such “surface-bound activators” may be beneficial for producing tissue-specific activation of the engineered Tregs. The surface can be the surface of a container (e.g., a plate, tube, bag, bioreactor, chamber, cassette, column), the surface of a bead (e.g., a microparticle, a microsphere), the surface of another cell (e.g., a target cell), or any other surface having a high degree of rigidity compared to the engineered Treg. The surface can be an organic surface, an inorganic surface, or a combination thereof. The activator can be directly attached to the surface, or can be indirectly attached to the surface via a carrier (e.g., a carrier protein, a carrier polymer, a carrier oligonucleotide, or any other bifunctional molecule capable of attaching to both the activator and to the surface). In some embodiments, a plurality of activators are attached to the surface at a sufficiently high density such that binding of two cytokine receptor chains to two proximate activators causes dimerization of the two cytokine receptor chains (e.g., homodimerization of two single-chain CCRs or heterodimerization of the two cytokine receptor chains of a dual-chain CCR). In other embodiments, however, the engineered Tregs may be activated by an activator that is not bound to any surface. For example, the activator can be provided as part of a free-floating, soluble activator-carrier complex. In some embodiments, the activator-carrier complex includes at least two activators such that binding of two cytokine receptor chains to two proximate activators causes dimerization of the two cytokine receptor chains (e.g., homodimerization of two single-chain CCRs or heterodimerization of the two cytokine receptor chains of a dual-chain CCR). Moreover, the engineered Tregs may also exhibit activator-independent activity in that signaling of the CCR may be initiated even in the absence of the activator, as described elsewhere herein. Fortem Ref. No. DCT.010WO III. Therapeutic Methods The engineered Tregs of the present technology may be administered to a subject to treat a disease or condition of the subject, such a disease or condition in which induction, restoration, and / or maintenance of immune tolerance is desirable. In some embodiments, the disease or condition is an autoimmune disease, such as Addison’s disease, amyotrophic lateral sclerosis (ALS), arthritis (e.g., rheumatoid arthritis), asthma, autoimmune atrophic gastritis, autoimmune hemolytic anemia, autoimmune uveitis, chronic action hepatitis, diabetes (e.g., insulin dependent diabetes mellitus, type I diabetes mellitus, type II diabetes mellitus), fibrotic disease (e.g., cystic fibrosis, systemic sclerosis, cardiac and liver fibrosis), Goodpasture syndrome, graft versus host disease (GvHD), Graves’ disease, Hashimoto’s thyroiditis, idiopathic thrombocytopenia, inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis), inclusion body myositis, hemophilia, lupus (e.g., lupus erythematosus, lupus nephritis), mixed connective tissue disease, multiple sclerosis (MS), myasthenia gravis, pemphigus, pernicious anemia, polymyositis, primary biliary cirrhosis, primary myxedema, psoriasis, scleroderma, Sjogren’s syndrome, sympathetic ophthalmia, and vitiligo. In some embodiments, the disease or condition is an inflammatory disease, such as arthritis; rheumatoid arthritis; ankylosing spondylitis; osteoarthritis; psoriatic arthritis; juvenile idiopathic arthritis; juvenile rheumatoid arthritis; arthritis uratica; gout; chronic polyarthritis; periarthritis humeroscapularis; cervical arthritis; lumbosacral arthritis; enteropathic arthritis; ankylosing spondylitis; asthma; dermatitis; psoriasis; scleroderma; polymyositis; dermatomyositis; juvenila dermatomyositis; primary biliary cirrhosis; fibrosis; cystic fibrosis; pulmonary fibrosis; cirrhosis; endomyocardial fibrosis; dediastinal fibrosis; myelofibrosis; retroperitoneal fibrosis; nephrogenic fibrosis; keloids; scleroderma; arthrofibrosis; post transplantation late and chronic solid organ rejection; multiple sclerosis; systemic lupus erythematosus; lupus nephritis; pemphigus; pemphigus vulgaris; pemphigus herpetiformis; pemphigus vegetans; IgA pemphigus; pemphigus erythematosus; bullous pemphigoid; pemphigoid gestationis; mucous membrane dermatosis; pemphigoid nodularis; linear IgA bullous dermatosis; bullous lichen planus; epidermolysis bullosa acquisita; autoimmune diabetes; diabetic retinopathy; diabetic nephropathy; diabetic vasculopathy; ocular inflammation; uveitis; rhinitis; ischemia-reperfusion injury; post-angioplasty restenosis; chronic obstructive pulmonary disease; glomerulonephritis; Graves’ disease; gastrointestinal allergies; conjunctivitis; atherosclerosis; coronary artery disease; angina; small artery disease; Fortem Ref. No. DCT.010WO acute disseminated encephalomyelitis; idiopathic thrombocytopenic purpura; multiple sclerosis; systemic sclerosis; antiphospholipid syndrome; Sjogren’s syndrome; autoimmune hemolytic anemia; colitis; Crohn’s Disease; ulcerative colitis; inflammatory bowel disease; embolism; pulmonary embolism; arterial embolism; venous embolism; allergic inflammation; cardiovascular disease; graft-related diseases; graft versus host disease; disorders associated with graft transplantation rejection, chronic rejection, and tissue or cell allografts or xenografts; autoimmune diseases; degeneration after trauma; stroke; transplant rejection; allergic conditions and hypersensitivity, e.g., allergic rhinitis, allergic eczema and the like; skin diseases; and dermal inflammatory disorders. In some embodiments, the disease or condition is organ or tissue transplantation, where the engineered Tregs are used to induce, increase, and / or maintain transplantation tolerance. In some embodiments, the subject is the recipient of an organ or tissue transplant (e.g., an allogeneic or xenogeneic transplant). In some embodiments, a method for treating a disease or condition includes administering a plurality of engineered Tregs to a subject. In some embodiments, between about 105and about 5 x 107engineered Tregs are administered to the subject. In some embodiments, between about 5 x 104and about 3 x 107engineered Tregs are administered to the subject. The engineered Tregs can include at least one engineered receptor that recognizes an activator. The method can further include administering an immune-activating agent to the subject, where the immune-activating agent includes the activator coupled to a targeting moiety that recognizes a marker on a target cell (e.g., an autoantigen or an antigen of an autoreactive inflammatory immune cell). In some embodiments, the engineered Tregs express a CCR that recognizes the activator, e.g., as described in Section I.A above. Binding of the CCR to the activator can elicit Treg activity that is beneficial for treatment of the disease or condition, e.g., maintenance of a desired phenotype, conversion to a desired phenotype, activation of cytokine signaling pathways, upregulation of immunosuppressive markers and / or cytokines, and / or improved cell proliferation and survival. The CCR may or may not be expressed with another engineered receptor that recognizes the same activator or a different activator, such as an indirect CAR. Engineered Tregs expressing a CCR may persist in a subject longer than a Treg that does not express a CCR. In some embodiments, a Treg expressing a CCR may persist in a subject for at least about 2 times, at least about 3 times, at least about 4 times, at least about 5 Fortem Ref. No. DCT.010WO times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 15 times, at least about 20 times, at least about 25 times, at least about 50 times, or at least about 100 times as long as a Treg that does not express a CCR. In some embodiments, a Treg expressing a CCR may persist in a subject for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days, at least about 16 days, at least about 18 days, at least about 20 days, at least about 22 days, at least about 24 days, at least about 26 days, at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, at least about 56 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 21 months, at least about 24 months, at least about 27 months, at least about 30 months, at least about 33 months, at least about 36 months, at least about 1 year, at least about 2 years, at least about 3 years, at least about 4 years, at least about 5 years, at least about 6 years, at least about 7 years, at least about 8 years, at least about 9 years, or at least about 10 years after being administered to the subject. In some embodiments, the engineered Tregs are CAR Tregs that express a CAR, e.g., as described in Section I.B above. The CAR of the CAR Tregs may be an indirect CAR that is engineered to recognize the activator. In such embodiments, administration of the activator with a targeting moiety that recognizes an antigen on a target cell (e.g., an autoantigen or an antigen of an autoreactive inflammatory immune cell) can target the CAR T-cells to the target cells to cause activation of the CAR. Alternatively, the CAR of the CAR Tregs may be a direct CAR that recognizes an antigen on a target cell (e.g., autoantigen or an antigen of an autoreactive inflammatory immune cell). In such embodiments, the direct CAR may be co-expressed with an engineered receptor that recognizes the activator, such as a CCR. Administration of the activator with a targeting moiety that recognizes an antigen on the target cells can facilitate targeting of the CAR T-cells to the target cells, whereupon the CAR of the CAR T-cells can recognize the antigen and induce Treg activation. Moreover, binding of the CCR to the activator may cause Fortem Ref. No. DCT.010WO activation of the CAR Tregs to maintain Treg phenotype, promote conversion to a memory Treg phenotype, maintain or activate immunosuppressive activity, etc. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes HLA-A2, CD19, or CD83 may be used to treat graft versus host disease. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes insulin, HiP2, or GAD65 beta- cell epitopes may be used to treat Type 1 diabetes. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes a citrullinated protein (e.g., citrullinated vimentin), a carbamylated protein, or type II collagen may be used to treat rheumatoid arthritis. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes myelin basic protein or myelin oligodendrocyte glycoprotein may be used to treat multiple sclerosis. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes ganglioside D3 (GD3) may be used to treat vitiligo. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes 2,4,6-trinitrophenol (TNP), carcinoembryonic antigen (CEA), or interleukin 23 receptor (IL23R) may be used to treat inflammatory bowel disease. In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes carcinoembryonic antigen (CEA) may be used to treat asthma. Fortem Ref. No. DCT.010WO In some embodiments, administration of a Treg engineered to express a CCR and / or an indirect CAR that recognizes an activator, and an immune-activating agent including the activator conjugated to a targeting moiety that recognizes Factor VIII (FVIII) may be used to treat hemophilia. The dosage of the immune-activating agent that is administered to the subject can be within a range from 0.1 mg / kg to 10 mg / kg, 0.1 mg / kg to 5 mg / kg, 0.1 mg / kg to 2 mg / kg, 0.1 mg / kg to 1 mg / kg, 0.1 mg / kg to 0.5 mg / kg, 0.5 mg / kg to 10 mg / kg, 0.5 mg / kg to 5 mg / kg, 0.5 mg / kg to 2 mg / kg, 0.5 mg / kg to 1 mg / kg, 1 mg / kg to 10 mg / kg, 1 mg / kg to 5 mg / kg, 1 mg / kg to 2 mg / kg, 2 mg / kg to 10 mg / kg, 2 mg / kg to 5 mg / kg, or 5 mg / kg to 10 mg / kg. In some embodiments, the immune-activating agent is administered to the subject at least 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, or 48 hours before the subject receives the engineered Tregs. Alternatively or in combination, the immune-activating agent may be administered to the subject concurrently with the engineered Tregs. Alternatively or in combination, the immune-activating agent is administered to the subject at least 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 24 hours, 36 hours, or 48 hours after the subject receives the engineered Tregs. In some embodiments, the immune-activating agent is administered to the subject a single time. Alternatively, the immune-activating agent may be administered to the subject multiple times, e.g., two, three, four, five, or more times. The administration frequency can be at any suitable time interval, such as daily, weekly, biweekly, monthly, yearly, etc. The immune-activating agent may be administered to the subject multiple times to re-activate the engineered Tregs so the engineered Tregs continue to exhibit activity that is beneficial for treatment of the disease, e.g., maintenance of the Treg phenotype, conversion to a memory Treg phenotype, maintenance or activation of immunosuppressive activity, etc. In some embodiments, the engineered Tregs may be re-activated about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, about 7 days, about 8 days, about 9 days, about 10 days, about 11 days, about 12 days, about 13 days, about 14 days, about 16 days, about 18 days, about 20 days, about 22 days, about 24 days, about 26 days, about 28 days, about 35 days, about 42 days, about 49 days, about 56 days, or combinations thereof, after being administered to the subject. In some embodiments, the engineered Tregs may be re-activated about 1 month, about 2 months, about 3 months, about 4 months, about 5 Fortem Ref. No. DCT.010WO months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 12 months, about 13 months, about 14 months, about 15 months, about 16 months, about 17 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months, about 36 months, or combinations thereof, after being administered to the subject. In some embodiments, the engineered Tregs may be re- activated about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, about 10 years, or combinations thereof, after being administered to the subject. In some embodiments, the engineered Tregs may be re-activated one or more times from about 7 days to about 56 days, from about 14 days to about 56 days, from about 21 days to about 56 days, from about 28 days to about 56 days, from about 35 days to about 56 days, from about 42 days to about 56 days, from about 49 days to about 56 days, from about 1 month to about 36 months, from about 2 months to about 36 months, from about 3 months to about 36 months, from about 4 months to about 36 months, from about 5 months to about 36 months, from about 6 months to about 36 months, from about 12 months to about 36 months, from about 18 months to about 36 months, from about 24 months to about 36 months, from about 30 months to about 36 months, from about 1 year to about 10 years, from about 2 years to about 10 years, from about 3 years to about 10 years, from about 4 years to about 10 years, from about 5 years to about 10 years, from about 1 years to about 8 years, from about 2 years to about 8 years, from about 3 years to about 8 years, from about 4 years to about 8 years, from about 5 years to about 8 years, from about 1 years to about 6 years, from about 2 years to about 6 years, from about 3 years to about 6 years, from about 4 years to about 6 years, or from about 5 years to about 6 years after being administered to the subject. The dosage of the immune-activating agent that is administered to the subject may be the same for some or all of the administrations, or may be different for some or all of the administrations. For instance, a first dosage of an immune-activating agent may be provided to the subject at a first time point; and a second, different dosage of the immune-activating agent may be provided to the subject at a second, later time point. The second dosage may be higher than, lower than, or the same as the first dosage. The first and second dosages may each be independently selected from any of the following: from 0.1 mg / kg to 10 mg / kg, 0.1 mg / kg to 5 mg / kg, 0.1 mg / kg to 2 mg / kg, 0.1 mg / kg to 1 mg / kg, 0.1 mg / kg to 0.5 mg / kg, 0.5 mg / kg to 10 mg / kg, 0.5 mg / kg to 5 mg / kg, 0.5 mg / kg to 2 mg / kg, 0.5 mg / kg to 1 mg / kg, 1 mg / kg to 10 mg / kg, 1 mg / kg to 5 mg / kg, 1 mg / kg to 2 mg / kg, 2 mg / kg to 10 mg / kg, 2 mg / kg to 5 mg / kg, Fortem Ref. No. DCT.010WO or 5 mg / kg to 10 mg / kg. In some embodiments, administration of different dosages at different times can be used to titrate the extent of Treg activation, e.g., to improve the efficacy of immunosuppression, to reduce off-target effects such as system immunosuppression, etc. In some embodiments, the immune-activating agent that is administered to the subject may be the same for some or all of the administrations, or may be different for some or all of the administrations. For instance, a first immune-activating agent including an activator and a first targeting moiety that recognizes a first antigen may be provided to the subject at a first time point; and a second immune-activating agent including the activator and a second targeting moiety that recognizes a second, different antigen may be provided to the subject at a second, later time point. This approach can be advantageous for directing the engineered Tregs to different antigens over time. In some embodiments, a plurality of different immune-activating agents are administered to the subject at the same time point. For example, a first immune-activating agent including an activator and a first targeting moiety that recognizes a first antigen may be provided to the subject at a time point; and a second immune-activating agent including the activator and a second targeting moiety that recognizes a second, different antigen may be provided to the subject at the same time point. This multiplexed approach can facilitate immune cell recognition of multiple antigens expressed on the same target cell and / or across multiple target cells, which may be advantageous for improving the specificity and efficacy of immunosuppression. As another example, a first immune-activating agent including a first activator and a targeting moiety that recognizes an antigen may be provided to the subject at a time point; and a second immune-activating agent including a second different, activator and a targeting moiety that recognizes an antigen may be provided to the subject at the same time point. The first activator may be recognized by a first engineered receptor of the immune cell (e.g., a CCR) and the second activator may be recognized by a second engineered receptor of the immune cell (e.g., an indirect CAR), thereby allowing for concurrent activation of both engineered receptors. The targeting moiety of the first immune-activating agent may be the same as the targeting moiety of the second immune-activating agent (e.g., both targeting moieties recognize the same antigen), or the targeting moiety of the first immune-activating agent may be different than the targeting moiety of the second immune-activating agent (e.g., the targeting moieties recognize different antigens). Fortem Ref. No. DCT.010WO In some embodiments, a method of treating a subject includes administering a first immune-activating agent to the subject, and administering a second immune-activating agent to the subject. For example, the first immune-activating agent can include a first activator for a CCR and a first targeting moiety; and the second immune-activating agent can include a second activator for an indirect CAR and a second targeting moiety. The first activator can be the same as the second activator, or the first activator can be different than the second activator. The first targeting moiety can be the same as the second targeting moiety, or the first targeting moiety can be different than the second targeting moiety. The first targeting moiety can recognize the same epitope as the second targeting moiety, or can recognize a different epitope than the second targeting moiety. The dosage of the first immune-activating agent can be the same as, greater than, or less than the dosage of the second immune-activating agent. The first immune-activating agent may be administered before, concurrently with, and / or after the second immune-activating agent. In some embodiments, the first immune-activating agent is administered at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days, at least about 16 days, at least about 18 days, at least about 20 days, at least about 22 days, at least about 24 days, at least about 26 days, at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, at least about 56 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months before the second immune-activating agent is administered. In some embodiments, the second immune-activating agent is administered at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days, at least about 16 days, at least about 18 days, at least about 20 days, at least about 22 days, at least about 24 days, at least about 26 days, at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, at least about 56 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at Fortem Ref. No. DCT.010WO least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months before the first immune-activating agent is administered. Optionally, in embodiments where the engineered Tregs express a CCR that exhibits activator-independent activity, the method may include inducing Treg activity without activating the immune cells with the activator. In some embodiments, the method includes maintaining the Treg phenotype, promoting conversion to a memory Treg phenotype, activating immunosuppressive activity, etc., via activator-independent activity of the CCR. The activator-independent activity can include dimerization of the CCR without binding of the activator to the CCR and / or interactions of the CCR with another receptor on the Treg (e.g., a CAR). In some embodiments, the immune-activating agent is administered to the subject after a delay period sufficient for activator-independent activity of the CCR to occur. For example, the delay period can be at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days, at least about 16 days, at least about 18 days, at least about 20 days, at least about 22 days, at least about 24 days, at least about 26 days, at least about 28 days, at least about 35 days, at least about 42 days, at least about 49 days, at least about 56 days, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months after the administration of the engineered Tregs. The administration of the immune-activating agent can cause in vivo activation of the CCR after the CCR has exhibited activator-independent activity. In some embodiments, the activator-independent activity causes induction of Treg activity, and the administration of the activator enhances the Treg activity. IV. Examples The present technology is further illustrated by the following non-limiting examples. Example 1: Development of CCRs for Immune Cell Activation This example describes development of CCRs for immune cell activation. Cytokine receptors were engineered to be activated by a fluorescein isothiocyanate (FITC) Fortem Ref. No. DCT.010WO small molecule activator. An intracellular signaling domain and transmembrane domain (TM) of an endogenous cytokine receptor were fused to a CD8α hinge, an activator binding domain (ABD) for a small molecule activator, such as an anti-FITC single-chain variable fragment (scFv), and a signal peptide (SP) of an endogenous cytokine receptor, as illustrated in FIG.4A. The CCRs were based on an IL2Rα, IL2Rβ, or IL2Rγ cytokine receptor. Sequences of the CCRs are provided in Table 1. SEQ ID NO: 1 contained an IL2Rα signaling peptide (SEQ ID NO: 16), an anti- FITC scFv (SEQ ID NO: 9), a CD8α hinge (SEQ ID NO: 22), an IL2Rα transmembrane domain (SEQ ID NO: 13), and an IL2Rα intracellular signaling domain (SEQ ID NO: 10). SEQ ID NO: 2 contained an IL2Rβ signal peptide (SEQ ID NO: 17), an anti-FITC scFv (SEQ ID NO: 9), a CD8α hinge (SEQ ID NO: 22), an IL2Rβ transmembrane domain (SEQ ID NO: 14), and an IL2Rβ intracellular signaling domain (SEQ ID NO: 11). SEQ ID NO: 3 contained an IL2Rγ signal peptide (SEQ ID NO: 18), an anti-FITC scFv (SEQ ID NO: 9), a CD8α hinge (SEQ ID NO: 22), an IL2Rγ transmembrane domain (SEQ ID NO: 15), and an IL2Rγ intracellular signaling domain (SEQ ID NO: 12). As shown in FIG.4B, a dual-chain CCR of SEQ ID NO: 7 contained an IL2Rβ signal peptide (SEQ ID NO: 17), an anti-FITC scFv (SEQ ID NO: 9), a CD8α hinge (SEQ ID NO: 22), an IL2Rβ transmembrane domain (SEQ ID NO: 14), an IL2Rβ intracellular signaling domain (SEQ ID NO: 11), a P2A peptide (SEQ ID NO: 24), an IL2Rγ signal peptide (SEQ ID NO: 18), an anti-FITC scFv (SEQ ID NO: 9), a CD8α hinge (SEQ ID NO: 22), an IL2Rγ transmembrane domain (SEQ ID NO: 15), an IL2Rγ intracellular signaling domain (SEQ ID NO: 12), a T2A peptide (SEQ ID NO: 25), and a truncated CD19 (SEQ ID NO: 23). The truncated CD19 included the entire extracellular and transmembrane domains and a truncated intracellular domain (cytoplasmic tail) to abrogate signaling. After translation, cleavage occurred at the P2A peptide and T2A peptide sequences, thus producing three separate proteins: (1) an engineered IL2Rβ cytokine receptor chain containing the IL2Rβ signal peptide (SEQ ID NO: 17), the anti-FITC scFv (SEQ ID NO: 9), the CD8α hinge (SEQ ID NO: 22), the IL2Rβ transmembrane domain (SEQ ID NO: 14), and the IL2Rβ intracellular signaling domain (SEQ ID NO: 11); (2) an engineered IL2Rγ cytokine receptor chain containing the IL2Rγ signal peptide (SEQ ID NO: 18), the anti-FITC scFv (SEQ ID NO: 9), the CD8α hinge (SEQ ID NO: 22), the IL2Rγ transmembrane domain (SEQ ID NO: 15), and the IL2Rγ intracellular signaling domain (SEQ ID NO: 12); and (3) the truncated CD 19 (SEQ ID NO: 23). Fortem Ref. No. DCT.010WO Example 2: Constructs for Expression of CCRs and / or CARs in Immune Cells This example describes constructs that may be used to express CCRs and / or CARs in an immune cell. FIG. 5A is a schematic illustration of a domain layout of a construct for expression of a CCR. As shown in FIG. 5A, the CCR includes a signal peptide (SP), an anti- small molecule binding domain, a hinge, a transmembrane domain (TM), and an intracellular domain (ICD)n. The construct also includes a 2A peptide or an IRES, and a marker. The signal peptide can be a signal peptide of IL2Rα, IL2Rβ, IL2Rγ, IL7Rα, IL15Rα, IL21Rα, IgG1, GM- CSF, etc. The anti-small molecule binding domain can be an scFv, VH, or VLof an anti-FITC antibody (e.g., 4M5.3), an anti-DOTA antibody (e.g., C8.2.5), an anti-MPOB antibody, etc. The hinge can be a hinge domain of CD8α, CD28, IgG1, IgG4, EpoR, etc. The transmembrane domain can be a transmembrane domain of IL2Rα, IL2Rβ, or IL2Rγ. The intracellular domain can be a single intracellular domain of IL2Rα, IL2Rβ, or IL2Rγ. Alternatively, the intracellular domain can be multiple intracellular domains of any of the above in tandem, such as two or more of the same intracellular domain or a combination of two or more different intracellular domains. The marker domain can be a truncated CD19 domain, a truncated CD34 domain, a fluorescent protein, etc. FIG. 5B is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR. As shown in FIG. 5B, the IL2Rβ / γ CCR includes a first cytokine receptor chain including an IL2Rβ signal peptide, an anti-FITC scFv, a CD8α hinge, an IL2Rβ transmembrane domain, and an IL2Rβ intracellular domain. The IL2Rβ / γ SMAR includes a second cytokine receptor chain including an IL2Rγ signal peptide, an anti-FITC scFv, a CD8α hinge, an IL2Rγ transmembrane domain, and an IL2Rγ intracellular domain. The first and second cytokine receptor chains are connected by a P2A peptide sequence. The construct also includes a T2A peptide sequence and a truncated CD19 marker domain. FIG. 5C is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR and an anti-DOTA indirect CAR. As shown in FIG.5C, the construct includes the first and second cytokine receptor chains of the IL2Rβ / γ CCR of FIG. 5B and an anti-DOTA indirect CAR linked to each other via 2A peptides. The anti-DOTA indirect CAR includes a CD8α signal peptide, an anti-DOTA scFv (c8.2.5), a CD8α hinge, a CD8α transmembrane domain, a 4-1BB intracellular domain, and a CD3ζ intracellular domain. Fortem Ref. No. DCT.010WO FIG. 5D is a schematic illustration of a domain layout of an example construct for expression of an IL2Rβ / γ CCR and an anti-FITC indirect CAR. As shown in FIG. 5D, the construct includes the first and second cytokine receptor chains of the IL2Rβ / γ CCR of FIG. 5B (except that the anti-FITC scFvs are replaced with anti-DOTA scFvs (c8.2.5)) and an anti- FITC indirect CAR linked to each other via 2A peptides. The anti-FITC indirect CAR includes a CD8α signal peptide, an anti-FITC scFv (4m5.3), a CD8α hinge, a CD8α transmembrane domain, a 4-1BB intracellular domain, and a CD3ζ intracellular domain. Example 3: Preparation and Characterization of Engineered Tregs This example describes the preparation and characterization of engineered Tregs with CCRs. Treg isolation, activation, transduction, expansion, and characterization. FIG. 6 schematically illustrates a process for preparation of engineered Tregs. Highly pure Treg cells were isolated from a healthy donor leukopak using the “CD4+CD25+CD127dim / -Reg TC Kit II, human” (Miltenyi Biotec #130-94-775), according to the manufacturer’s instructions. Treg cells from two different donors were obtained. Tregs were then activated with anti-CD3 / CD28- coated beads, either Dynabeads Human Treg Expander beads (Life Technologies #11129D) (“Dynabeads”) or Treg expansion kit MACS iBeads (Miltenyi #130-95-353) (“MACS iBeads”) in the presence of varying concentrations of IL-2 from 0 to 500 U / mL. On Day 1 after activation, Tregs were either transduced with a lentiviral vector encoding a dual-chain anti- fluorescein-IL-2Rβ and anti-fluorescein-IL-2Rγ CCR (“IL-2Rβγ CCR,” SEQ ID NO: 8), or left untransduced (“UTD”) as a negative control. Treg cells were counted, expanded, and provided with fresh media every 2 to 3 days until Day 14 after activation. In some cases, Tregs were restimulated with additional Dynabeads or MACS iBeads on Day 8 after activation, as indicated. In some cases, FITC-1kPEG-conjugated Dynabeads (“FITC-1kPEG beads”) were added at a 5:1 bead:cell ratio at Day 3 and Day 8 for CCR activation. On Day 14, Tregs were harvested and de-beaded using a magnet. Then, harvested Tregs were analyzed by flow cytometry for purity (CD3+, CD4+, CD8-, CD25hi, CD127lo, FoxP3+), memory phenotype (CD45RA, CCR7), and immunosuppressive markers (Helios, CTLA-4, PD-1, LAG-3), and remaining cells were cryopreserved using CS10 (Stem Cell Technologies #07930) for future experiments. Flow cytometry data was collected on a BD Fortessa using FACSDiva software and analyzed using FlowJo, LLC software. Fortem Ref. No. DCT.010WO FIG. 7 is a series of graphs illustrating purity of engineered Tregs. Processing of half of a leukopak yielded approximately 6 x 106Tregs. As shown in FIG.7, Tregs remained highly pure after the expansion and isolation process, with Tregs made with Miltenyi MACS iBeads maintaining higher purity after expansion than Tregs made with Dynabeads. FIG. 8A is a series of graphs showing Treg expansion (top row) and viability (bottom row) over time at various concentrations of IL-2 (0, 20, 100, and 500 U / mL). Tregs were either untransduced or transduced to express an IL-2Rβγ CCR. For each construct, Treg persistence was evaluated both with and without presence of FITC-1kPEG beads, which activate the CCR. The experimental groups are shown in Table 9 below. Table 9: Experimental Groups Construct IL-2 (U / mL) CCR Activator UTD 0 None 20 None 100 None 500 None 0 FITC-1kPEG beads 20 FITC-1kPEG beads 100 FITC-1kPEG beads 500 FITC-1kPEG beads IL-2Rβγ CCR 0 None 20 None 100 None 500 None 0 FITC-1kPEG beads 20 FITC-1kPEG beads 100 FITC-1kPEG beads 500 FITC-1kPEG beads As shown in FIG. 8A, the presence of IL-2Rβγ CCRs did not replace IL-2 supplementation but did improve viability in low IL-2 conditions compared to UTD controls. Fortem Ref. No. DCT.010WO FIG. 8B is a series of graphs showing Treg viability at Day 14 at various concentrations of IL-2. The presence of IL-2Rβγ CCRs did not replace IL-2 supplementation but maintained improved viability in low IL-2 conditions compared to UTD controls. FIG.9A is a graph illustrating expansion of Tregs with and without the IL-2Rβγ CCR, and FIG. 9B is a graph illustrating purity of Tregs with and without the IL-2Rβγ CCR. Under high IL-2 conditions (500 U / mL), there were no major differences in the expansion or purity of UTD Tregs versus IL-2Rβγ CCR Tregs. FIG.10 is a series of graphs illustrating FoxP3+Helios+ coexpression in Tregs. FoxP3 is a Treg phenotype marker, and Helios is a marker of Treg stability. As shown in the graphs of FIG. 10, Tregs generated using MACS iBeads displayed a slight increase in FOXP3 and Helios co-expression compared to Tregs generated using Dynabeads. FIG. 11 is a graph showing Treg purity in the presence and absence of CCR activation. As shown in the graphs of FIG. 11, Tregs expressing the IL-2Rβγ CCR were enriched at lower IL-2 conditions both in the presence and absence of CCR activation by FITC- 1kPEG beads. This suggests that Tregs expressing the IL-2Rβγ CCR may have a survival advantage due to some level of activator-independent CCR signaling activity. FIG. 12A is a series of flow cytometry plots showing expression of memory phenotype markers CD45RA and CCR7 in Tregs with and without the IL-2Rβγ CCR, and FIG. 12B is a graph illustrating the distribution of four Treg memory phenotypes: naïve (CD45RA+CCR7+), central memory (Tcm) (CD45RA-CC7+), effector memory (Tem) (CD45RA-CCR7-), and effector memory re-expressing CD45RA (Temra) (CD45RA+CCR7- ). Tregs with the IL-2Rβγ CCR exhibited an increase in Tcm Treg memory phenotype and a reduction in Tem and Temra phenotypes. FIGS.12C and 12D are graphs showing the prevalence of various Treg memory phenotypes for Tregs generated with Dynabeads versus MACS iBeads. Tregs with the IL-2Rβγ CCR exhibited a slight increase in Tcm and Tscm Treg memory phenotypes and a reduction in Temra phenotype. FIG.13A is a series of graphs showing expression of CTLA-4 in Tregs with and without the IL-2Rβγ CCR. As shown in FIG. 13A, IL-2Rβγ CCRs induced increased surface expression of CTLA-4, an important immunosuppressive marker. FIG.13B is a series of graphs showing expression of CTLA-4 in Tregs with and without the IL-2Rβγ CCR, for Tregs generated with Dynabeads versus MACS iBeads. As Fortem Ref. No. DCT.010WO shown in FIG. 13B, IL-2Rβγ CCRs induced increased surface and intracellular expression of CTLA-4 both with and without CCR activation. FIG. 14A is a series of flow cytometry plots showing expression of immunosuppressive markers PD-1 and LAG3 in Tregs, and FIG.14B provides graphs showing the percentage of Tregs expressing each marker. As shown in FIGS. 14A and 14B, Tregs with the IL-2Rβγ CCR exhibited increased expression of PD-1 and LAG3 compared to UTD Tregs. FIGS. 14C and 14D are a series of graphs showing expression of PD-1 and LAG3 in Tregs with and without the IL-2Rβγ CCR, for Tregs generated with Dynabeads versus MACS iBeads. Tregs with the IL-2Rβγ CCR exhibited increased expression of PD-1 and LAG3, particularly for Tregs generated with Dynabeads. These results demonstrate that the IL-2Rβγ CCR improved Treg survival in low IL-2 conditions, with or without CCR activation by FITC-1kPEG beads. Moreover, IL-2Rβγ CCR expressing cells were enriched in low IL-2 conditions. IL-2Rβγ CCR Tregs exhibited increased Tscm and Tcm memory phenotypes and reduced Temra phenotype, with or without CCR activation by FITC-1kPEG beads. IL-2Rβγ CCR Tregs also induce surface and intracellular CTLA-4 expression. These effects were observed in the absence of CCR activator, thus suggesting that the IL-2Rβγ CCR exhibits activator-independent signaling activity. There were some differences observed between Tregs generated with MACS iBeads versus Dynabeads. In particular, MACS iBeads increased expanded Treg purity and co- expression of FoxP3 with Helios, while Dynabeads increased PD-1 and LAG-3 expression in CCR Tregs. Example 4: Treg Functional Assessment: Immunosuppression Assay This example describes functional assays used to assess the immunosuppressive capability of the Tregs in accordance with the present technology. Conventional T cell isolation, activation, and expansion. Donor-matched CD4+CD25- conventional T (Tconv) cells were isolated by collecting the non-Treg fraction of cells during the Treg isolation described in Example 3 above. Tconv cells were activated with anti-CD3 / CD28-coated Dynabead T-Activator (Life Technologies #11132D) with 100 U / mL IL-2. Tconv cells were counted, expanded, and provided with fresh media every 2 to 3 days until Day 10 after activation. On Day 10, Tconv cells were de-beaded using a magnet, analyzed by flow cytometry, and cryopreserved for future experiments. Fortem Ref. No. DCT.010WO Treg functional assessment via immunosuppression assay. FIG. 15 schematically illustrates an immunosuppression assay for assessing Treg function. UTD or IL- 2Rβγ CCR Tregs generated via either Dynabeads or MACS iBeads according to the protocols of Example 3 above were thawed into cell culture medium. Tconv cells were also thawed and labeled with Cell Trace Violet (CTV) dye (Life Technologies #C34557). UTD or IL-2Rβγ CCR Tregs were co-cultured with CTV-labeled Tconv cells at various Treg: Tconv cell ratios (2:1, 1:1, 1:2, 1:4, 1:8) and activated with Dynabead T-Activator (Life Technologies #11132D) and a 1:10 bead:Tconv cell ratio. Additionally, Tconv cells were cultured alone in the presence or absence of Dynabeads for comparison. Additionally, UTD or IL-2Rβγ CCR Tregs were co- cultured with CTV-labeled Tconv cells at a 2:1 ratio in the absence of stimulation with Dynabeads. Finally, UTD or IL-2Rβγ CCR Tregs were cultured alone in the presence of Dynabead stimulation. Cells were cultured at 37°C, 5% CO2 for 4 days. Cells were then analyzed by flow cytometry for cell viability, CTV dye, and CD25 expression. As shown in the left graph of FIG.16, CTV-labeled Tconv cells cultured alone in the presence of stimulation exhibit CTV dye dilution, with the number of peaks at decreasing mean fluorescence intensity (MFI) corresponding to the number of cell divisions, while non-stimulated Tconv cells showed minimal CTV dilution, maintaining high MFI. Tregs were expected to prevent or reduce Tconv cell division, and thus prevent CTV dilution. Treg suppression was calculated using the following equation: %^^^^^^^^^^^^^^^^^^^^^^ ൌ 100 The division index (DI) was determined by FlowJo, LLC software using the “Proliferation Modeling” tool. DI is an estimate of the number of divisions an average cell in a population has undergone (a lower DI indicates less cell proliferation). FIG. 16 provides flow cytometry plots illustrating an example of Treg immunosuppression of Tconv cell proliferation, indicated by the reduced number of CTV dilution peaks for Tconv cells cultured with Tregs (right) versus Tconv cells cultured alone (left). FIG. 17 is a series of graphs showing Treg suppression of Tconv proliferation for Tregs with and without the IL-2Rβγ CCR, and generated using Dynabeads or MACS iBeads. As shown in the graphs of FIG. 17, Tregs with the IL-2Rβγ CCR increased the suppression of Tconv (conventional T cell) proliferation, especially in Tregs generated using Fortem Ref. No. DCT.010WO MACS iBeads. These effects were observed in the absence of CCR activation by FITC-1kPEG beads. FIG. 18 is a series of graphs showing Treg viability in the immunosuppression assay. As shown in the graphs of FIG. 18, the presence of IL-2Rβγ CCRs appeared to increase Treg viability in populations generated from both Dynabeads and MACS iBeads. These effects were observed in the absence of CCR activation by FITC-1kPEG beads. Overall, these results demonstrate that IL-2Rβγ CCR Tregs exhibited increased immunosuppressive capability that correlated with improved viability. These effects were observed in the absence of CCR activator, thus suggesting that the IL-2Rβγ CCR exhibits activator-independent signaling activity. Example 5: In Vitro Evaluation of Treg Stability This example describes studies to evaluate engineered Treg stability in the presence of inflammatory cytokines. UTD or IL-2Rβγ CCR Treg cells will be cultured in the presence of a cocktail of inflammatory cytokines, such as IL-1β, IL-6, IL-21, IL-23, and TGFβ, which are cytokines that drive an inflammatory Th17 cell phenotype. Tregs will be cultured in the presence of the inflammatory cytokine cocktails for 4 to 5 days. Cell supernatants will be collected and evaluated for IL-17 production, the key Th17 cytokine. Treg cells will be collected and evaluated by flow cytometry for expression of FoxP3, Helios, and the Th17 master transcription factor, RORγt. IL-2Rβγ CCR Tregs are expected to have reduced expression of Th17 factors, IL-17 and RORγt, as well as to have maintained high expression of FoxP3 and Helios, compared to UTD Tregs. These results will demonstrate the ability of the IL-2Rβγ CCR to maintain Treg stability in inflammatory and / or autoimmune microenvironments, such as an inflamed, arthritic joint. Example 6: In Vivo Evaluation of Treg Persistence and Activity This example describes studies to evaluate the persistence and activity of engineered Tregs in vivo. NSG mice will be infused with UTD or IL-2Rβγ CCR Tregs. Blood, spleen, lung, liver samples will be collected and evaluated for the persistence of Tregs at Day 7 and 14 after infusion. It is expected that IL-2Rβγ CCR Tregs will have improved persistence compared to UTD Tregs, due to the increased survival observed in low IL-2 environments in vitro. Fortem Ref. No. DCT.010WO To assess the ability of the engineered Tregs to suppress graft versus host disease (GvHD) in vivo, NSG mice will be infused with UTD or IL-2R^^ CCR Tregs and allo- reactive donor-mismatched human peripheral blood mononuclear cells (PBMCs), or PBMCs alone. NSG mice infused with PBMCs alone will develop GvHD, and mice will come to humane endpoints within two weeks. The co-infusion of Tregs is expected to delay GvHD. It is expected that IL-2R^^ CCR Tregs will extend the survival of allo-PBMC-infused NSG mice to a longer endpoint compared to UTD Tregs, due to the increased persistence, survival and suppressive capability observed in vitro. V. Additional Examples Additional examples of aspects of the present technology are described below as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the subject technology. Example 1. A composition for immunotherapy, the composition comprising: an engineered regulatory T-cell (Treg), wherein the engineered Treg expresses a chimeric cytokine receptor (CCR) comprising: an activator binding domain configured to bind an activator, wherein the activator is an exogenous small molecule; a transmembrane domain; and an intracellular domain; wherein at least one of the transmembrane domain or the intracellular domain comprises or is derived from an interleukin 2 receptor (IL2R) domain. Example 2. The composition of Example 1, wherein the transmembrane domain comprises or is derived from a transmembrane domain of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ). Example 3. The composition of Example 1 or 2, wherein the transmembrane domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 13 – SEQ ID NO: 15. Example 4. The composition of any one of Examples 1 to 3, wherein the transmembrane domain comprises a sequence of any one of SEQ ID NO: 13 – SEQ ID NO: 15. Fortem Ref. No. DCT.010WO Example 5. The composition of any one of Examples 1 to 4, wherein the intracellular domain comprises or is derived from an intracellular domain of an IL2Rα, an IL2Rβ, an IL2Rγ, a TGFβ receptor I subunit, or a TGFβ receptor II subunit. Example 6. The composition of any one of Examples 1 to 5, wherein the intracellular domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 10 – SEQ ID NO: 12. Example 7. The composition of any one of Examples 1 to 6, wherein the intracellular domain comprises a sequence of any one of SEQ ID NO: 10 – SEQ ID NO: 12. Example 8. The composition of any one of Examples 1 to 7, wherein binding of the activator to the activator binding domain causes one or more of the following: maintenance of a Treg phenotype, conversion to a Treg memory phenotype, maintenance or upregulation of immunosuppressive activity, increased Treg proliferation, or improved Treg survival. Example 9. The composition of any one of Examples 1 to 8, wherein binding of the activator to the activator binding domain causes activation of a STAT5 signaling pathway. Example 10. The composition of any one of Examples 1 to 9, wherein binding of the activator to the activator binding domain causes upregulation of one or more of the following: FOXP3, Helios, interleukin 10 (IL10), interleukin 35 (IL35), TGFβ, CTLA-4, PD- 1, LAG3, or CCR7. Example 11. The composition of any one of Examples 1 to 10, wherein the activator binding domain comprises a single-chain variable fragment (scFv). Example 12. The composition of any one of Examples 1 to 11, wherein the activator binding domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO: 9. Example 13. The composition of any one of Examples 1 to 12, wherein the activator binding domain comprises a sequence of SEQ ID NO: 9. Example 14. The composition of any one of Examples 1 to 13, wherein the activator has a molecular weight less than or equal to 5 kDa, 4 kDa, 3 kDa, 2 kDa, 1 kDa, 500 Da, 200 Da, or 100 Da. Fortem Ref. No. DCT.010WO Example 15. The composition of any one of Examples 1 to 14, wherein the activator is selected from the group consisting of fluorescein, fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, 6- FAM phosphoramidite, topiramate hemisuccinate, creatine, acetaminophen, ketamine, propofol, lidocaine, ractopamine, salicylate, salicylic acid, sulfasalazine, dapsone, albendazole, ivermectin, levamisole, permethrin, pyrantel, thiabendazole, procainamide, sulfamethazine, amikacin, amoxicillin, ampicillin, cefazolin, cefuroxime, cephalexin, chloramphenicol, chloramphenicol, ciprofloxacin, clenbuterol, cloxacillin, colistin A, dicloxacillin, enrofloxacin, furaltadone, gentamicin, gentamicin, kanamycin, kanamycin, kincomycin, lincomycin, metronidazole, nafcillin, nalidixic acid, neomycin, neomycin, nitrofurazone, norfloxacin, ofloxacin, oxacillin, spectinomycin, streptomycin, streptomycin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadimidine, sulfametoxydiazine, sulfanilamide, trimethoprim, carbamazepine, ethosuximide, lamotrigine, primidone, cetirizine, chlorpheniramine, diphenhydramine, doxylamine, promethazine, sulfadimethoxine, benzothiazinone, butylated hydroxytoluene, tripelennamine, chlorpromazine, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, ribavirin, meprobamate, acebutolol, atenolol, penbutolol, warfarin, salmeterol, aflatoxin B1, tetraxetan (DOTA), 4-[(6-methylpyrazin-2-yl) oxy]benzoate (MPOB), biotin, melamine, methotrexate, amphetamine, diethylpropion, dextromethorphan, pseudoephedrine, dihydrochlorothiazide, hydrochlorothiazide, clonazepam, diazepam, nitrazepam, rhodamine B, fluorescent brightener Ksn, zearalenone, Sudan Red1, acetaminophen, acrylamide, benzoic acid, benzophenone, benzothiazine, mercaptobenzothiazole, erythrosine, Sudan, tartrazine, erythromycin, sirolimus, atropine, ethyl glucuronide, aflatoxin M1, methocarbamol, fentanyl, hydromorphone, morphine, remifentanil, tapentadol, tramadol, pregabalin, gabapentin, amitriptyline, desipramine, imipramine, nortriptyline, venlafaxine, dinitrophenyl, His-tag, PEG methoxy group, etodolac, ibuprofen, ketoprofen, meclofenamic acid, phenylbutazone, acetyl salicylic acid, acetamiprid, acetochlor, carbadazim, carbaryl, chlorothalonil, chlorpyrifos, fenpropathrin, imazalil, imidacloprid, parathion, abscisic acid, dibutyl phthalate, clonazepam, lorazepam, oxazepam, phenobarbital, secobarbital, zaleplon, zolpidem, trazodone, fluoxetine, fluvoxamine, cortisone, dexamethasone, dihydrotestosterone, fluocinolone, methylprednisolone, prednisolone, stanozolol, triamcinolone, mazindol, methamphetamine, methylphenidate, modafinil, chrysoidine, deoxynivalenol, fumonisin, microcystin Lr, ochratoxin, sterigmatocystin, T-2 toxin, sildenafil, tadalafil, scopolamine, florfenicol, pirlimycin, and sulfaquinoxaline. Fortem Ref. No. DCT.010WO Example 16. The composition of any one of Examples 1 to 15, wherein the activator is fluorescein, a fluorescein derivative, or tetraxetan (DOTA). Example 17. The composition of Example 16, wherein the activator is the fluorescein derivative, and the fluorescein derivative is wherein the fluorescein derivative is fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, or 6-FAM phosphoramidite. Example 18. The composition of any one of Examples 1 to 17, wherein the CCR comprises: a first cytokine receptor chain comprising the activator binding domain, the transmembrane domain, and the intracellular domain, and a second cytokine receptor chain comprising: a second activator binding domain configured to bind the activator; a second transmembrane domain comprising or derived from an IL2R transmembrane domain; and a second intracellular domain comprising or derived from an IL2R intracellular domain. Example 19. The composition of Example 18, wherein: the transmembrane domain comprises or is derived from an IL2Rβ transmembrane domain, the intracellular domain comprises or is derived from an IL2Rβ intracellular domain, the second transmembrane domain comprises or is derived from an IL2Rγ transmembrane domain, and the second intracellular domain comprises or is derived from an IL2Rγ intracellular domain. Example 20. The composition of any one of Examples 1 to 19, wherein the CCR comprises a hinge domain. Example 21. The composition of Example 20, wherein the hinge domain comprises or is derived from a hinge domain of a CD8, a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an ICOS, a CD27, an immunoglobulin, or an EpoR. Example 22. The composition of Example 20 or 21, wherein the hinge domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO: 22. Fortem Ref. No. DCT.010WO Example 23. The composition of any one of Examples 20 to 22, wherein the hinge domain comprises a sequence of SEQ ID NO: 22. Example 24. The composition of any one of Examples 1 to 23, wherein the CCR comprises a signal peptide. Example 25. The composition of Example 24, wherein the signal peptide is comprises or is derived from a signal peptide of an IL2Rα, an IL2Rβ, anIL2Rγ, an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), a CD130, an immunoglobulin, a CD8, a CD28, or a GM-CSF. Example 26. The composition of Example 24 or 25, wherein the signal peptide comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 16 – SEQ ID NO: 21. Example 27. The composition of any one of Examples 24 to 26, wherein the signal peptide comprises a sequence of any one of SEQ ID NO: 16 – SEQ ID NO: 21. Example 28. The composition of any one of Examples 1 to 27, wherein the CCR comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 1 – SEQ ID NO: 4. Example 29. The composition of any one of Examples 1 to 28, wherein the CCR comprises a sequence of any one of SEQ ID NO: 1 – SEQ ID NO: 4. Example 30. The composition of any one of Examples 1 to 29, wherein the CCR is encoded by a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 5 – SEQ ID NO: 8. Fortem Ref. No. DCT.010WO Example 31. The composition of any one of Examples 1 to 30, wherein the CCR is encoded by a sequence of any one of SEQ ID NO: 5 – SEQ ID NO: 8. Example 32. The composition of any one of Examples 1 to 31, wherein the engineered Treg expresses a chimeric antigen receptor (CAR). Example 33. The composition of Example 32, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain. Example 34. The composition of Example 33, wherein the antigen binding domain binds to a synthetic antigen. Example 35. The composition of Example 34, wherein the synthetic antigen is the activator. Example 36. The composition of Example 34, wherein the synthetic antigen is different than the activator. Example 37. The composition of Example 33, wherein the antigen binding domain binds to an autoantigen. Example 38. The composition of Example 37, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. Example 39. The composition of Example 33, wherein the antigen binding domain binds to an antigen on an autoreactive inflammatory immune cell. Example 40. The composition of Example 39, wherein the antigen is interleukin 23 receptor (IL23R) or CD83. Example 41. The composition of any one of Examples 1 to 31, wherein the engineered Treg does not express any CAR. Example 42. A pharmaceutical composition comprising the composition of any one of Examples 1 to 41 and a pharmaceutically acceptable carrier. Example 43. A system for immunotherapy, the system comprising: the composition of any one of Examples 1 to 41 or the pharmaceutical composition of Example 42; and Fortem Ref. No. DCT.010WO an immune-activating agent comprising the activator coupled to a targeting moiety, wherein the targeting moiety binds to a marker on a target cell. Example 44. The system of Example 43, wherein the targeting moiety comprises an antibody, an antibody fragment, a scFv, a nanobody, or a peptide. Example 45. The system of Example 43 or 44, wherein the marker is an autoantigen. Example 46. The system of Example 45, wherein the autoantigen is expressed by a healthy cell of a subject. Example 47. The system of Example 45 or 46, wherein the autoantigen is expressed by a cell of a transplanted organ or tissue of a subject. Example 48. The system of any one of Examples 45 to 47, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. Example 49. The system of Example 43 or 44, wherein the marker is an antigen expressed by an autoreactive immune cell. Example 50. The system of Example 49, wherein the antigen is interleukin 23 receptor (IL23R) or CD83. Example 51. A method for treating a disease or condition, the method comprising administering the composition of any one of Examples 1 to 41, the pharmaceutical composition of Example 42, or the system of any one of Examples 41 to 50 to a subject. Example 52. A method for treating a disease or condition, the method comprising: administering an engineered regulatory T-cell (Treg) to a subject, wherein the engineered Treg expresses a chimeric cytokine receptor (CCR) comprising: an activator binding domain configured to bind an activator, wherein the activator is an exogenous small molecule; a transmembrane domain; and an intracellular domain, Fortem Ref. No. DCT.010WO wherein at least one of the transmembrane domain or the intracellular domain comprises or is derived from an interleukin 2 receptor (IL2R) domain. Example 53. The method of Example 52, wherein the transmembrane domain comprises or is derived from a transmembrane domain of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ). Example 54. The method of Example 52 or 53, wherein the transmembrane domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 13 – SEQ ID NO: 15. Example 55. The method of any one of Examples 52 to 54, wherein the transmembrane domain comprises a sequence of any one of SEQ ID NO: 13 – SEQ ID NO: 15. Example 56. The method of any one of Examples 52 to 55, wherein the intracellular domain comprises or is derived from an intracellular domain of an IL2Rα, an IL2Rβ, an IL2Rγ, a TGFβ receptor I subunit, or a TGFβ receptor II subunit. Example 57. The method of any one of Examples 52 to 56, wherein the intracellular domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 10 – SEQ ID NO: 12. Example 58. The method of any one of Examples 52 to 57, wherein the intracellular domain comprises a sequence of any one of SEQ ID NO: 10 – SEQ ID NO: 12. Example 59. The method of any one of Examples 52 to 58, wherein binding of the activator to the activator binding domain causes one or more of the following: maintenance of a Treg phenotype, conversion to a Treg memory phenotype, maintenance or upregulation of immunosuppressive activity, increased Treg proliferation, or improved Treg survival. Example 60. The method of any one of Examples 52 to 59, wherein binding of the activator to the activator binding domain causes activation of a STAT5 signaling pathway. Fortem Ref. No. DCT.010WO Example 61. The method of any one of Examples 52 to 60, wherein binding of the activator to the activator binding domain causes upregulation of one or more of the following: FOXP3, Helios, interleukin 10 (IL10), interleukin 35 (IL35), TGFβ, CTLA-4, PD- 1, LAG3, or CCR7. Example 62. The method of any one of Examples 52 to 61, wherein the activator binding domain comprises a single-chain variable fragment (scFv). Example 63. The method of any one of Examples 52 to 62, wherein the activator binding domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO: 9. Example 64. The method of any one of Examples 52 to 63, wherein the activator binding domain comprises a sequence of SEQ ID NO: 9. Example 65. The method of any one of Examples 52 to 64, wherein the activator has a molecular weight less than or equal to 5 kDa, 4 kDa, 3 kDa, 2 kDa, 1 kDa, 500 Da, 200 Da, or 100 Da. Example 66. The method of any one of Examples 52 to 65, wherein the activator is selected from the group consisting of fluorescein, fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, 6- FAM phosphoramidite, topiramate hemisuccinate, creatine, acetaminophen, ketamine, propofol, lidocaine, ractopamine, salicylate, salicylic acid, sulfasalazine, dapsone, albendazole, ivermectin, levamisole, permethrin, pyrantel, thiabendazole, procainamide, sulfamethazine, amikacin, amoxicillin, ampicillin, cefazolin, cefuroxime, cephalexin, chloramphenicol, chloramphenicol, ciprofloxacin, clenbuterol, cloxacillin, colistin A, dicloxacillin, enrofloxacin, furaltadone, gentamicin, gentamicin, kanamycin, kanamycin, kincomycin, lincomycin, metronidazole, nafcillin, nalidixic acid, neomycin, neomycin, nitrofurazone, norfloxacin, ofloxacin, oxacillin, spectinomycin, streptomycin, streptomycin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadimidine, sulfametoxydiazine, sulfanilamide, trimethoprim, carbamazepine, ethosuximide, lamotrigine, primidone, cetirizine, chlorpheniramine, diphenhydramine, doxylamine, promethazine, sulfadimethoxine, benzothiazinone, butylated hydroxytoluene, tripelennamine, chlorpromazine, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, ribavirin, meprobamate, acebutolol, atenolol, penbutolol, warfarin, salmeterol, aflatoxin B1, tetraxetan (DOTA), 4-[(6-methylpyrazin-2-yl) oxy]benzoate (MPOB), biotin, melamine, methotrexate, amphetamine, diethylpropion, dextromethorphan, Fortem Ref. No. DCT.010WO pseudoephedrine, dihydrochlorothiazide, hydrochlorothiazide, clonazepam, diazepam, nitrazepam, rhodamine B, fluorescent brightener Ksn, zearalenone, Sudan Red1, acetaminophen, acrylamide, benzoic acid, benzophenone, benzothiazine, mercaptobenzothiazole, erythrosine, Sudan, tartrazine, erythromycin, sirolimus, atropine, ethyl glucuronide, aflatoxin M1, methocarbamol, fentanyl, hydromorphone, morphine, remifentanil, tapentadol, tramadol, pregabalin, gabapentin, amitriptyline, desipramine, imipramine, nortriptyline, venlafaxine, dinitrophenyl, His-tag, PEG methoxy group, etodolac, ibuprofen, ketoprofen, meclofenamic acid, phenylbutazone, acetyl salicylic acid, acetamiprid, acetochlor, carbadazim, carbaryl, chlorothalonil, chlorpyrifos, fenpropathrin, imazalil, imidacloprid, parathion, abscisic acid, dibutyl phthalate, clonazepam, lorazepam, oxazepam, phenobarbital, secobarbital, zaleplon, zolpidem, trazodone, fluoxetine, fluvoxamine, cortisone, dexamethasone, dihydrotestosterone, fluocinolone, methylprednisolone, prednisolone, stanozolol, triamcinolone, mazindol, methamphetamine, methylphenidate, modafinil, chrysoidine, deoxynivalenol, fumonisin, microcystin Lr, ochratoxin, sterigmatocystin, T-2 toxin, sildenafil, tadalafil, scopolamine, florfenicol, pirlimycin, and sulfaquinoxaline. Example 67. The method of any one of Examples 52 to 66, wherein the activator is fluorescein, a fluorescein derivative, or tetraxetan (DOTA). Example 68. The method of Example 67, wherein the activator is the fluorescein derivative, and the fluorescein derivative is wherein the fluorescein derivative is fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, or 6-FAM phosphoramidite. Example 69. The method of any one of Examples 52 to 68, wherein the CCR comprises: a first cytokine receptor chain comprising the activator binding domain, the transmembrane domain, and the intracellular domain, and a second cytokine receptor chain comprising: a second activator binding domain configured to bind the activator; a second transmembrane domain comprising or derived from an IL2R transmembrane domain; and a second intracellular domain comprising or derived from an IL2R intracellular domain. Fortem Ref. No. DCT.010WO Example 70. The method of Example 69, wherein: the transmembrane domain comprises or is derived from an IL2Rβ transmembrane domain, the intracellular domain comprises or is derived from an IL2Rβ intracellular domain, the second transmembrane domain comprises or is derived from an IL2Rγ transmembrane domain, and the second intracellular domain comprises or is derived from an IL2Rγ intracellular domain. Example 71. The method of any one of Examples 52 to 70, wherein the CCR comprises a hinge domain. Example 72. The method of Example 71, wherein the hinge domain comprises or is derived from a hinge domain of a CD8, a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an ICOS, a CD27, an immunoglobulin, or an EpoR. Example 73. The method of Example 71 or 72, wherein the hinge domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO: 22. Example 74. The method of any one of Examples 71 to 73, wherein the hinge domain comprises a sequence of SEQ ID NO: 22. Example 75. The method of any one of Examples 52 to 74, wherein the CCR comprises a signal peptide. Example 76. The method of Example 75, wherein the signal peptide is comprises or is derived from a signal peptide of an IL2Rα, an IL2Rβ, anIL2Rγ, an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), a CD130, an immunoglobulin, a CD8, a CD28, or a GM-CSF. Example 77. The method of Example 75 or 76, wherein the signal peptide comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, Fortem Ref. No. DCT.010WO 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 16 – SEQ ID NO: 21. Example 78. The method of any one of Examples 75 to 77, wherein the signal peptide comprises a sequence of any one of SEQ ID NO: 16 – SEQ ID NO: 21. Example 79. The method of any one of Examples 52 to 78, wherein the CCR comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 1 – SEQ ID NO: 4. Example 80. The method of any one of Examples 52 to 79, wherein the CCR comprises a sequence of any one of SEQ ID NO: 1 – SEQ ID NO: 4. Example 81. The method of any one of Examples 52 to 80, wherein the CCR is encoded by a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 5 – SEQ ID NO: 8. Example 82. The method of any one of Examples 52 to 81, wherein the CCR is encoded by a sequence of any one of SEQ ID NO: 5 – SEQ ID NO: 8. Example 83. The method of any one of Examples 52 to 82, wherein the engineered Treg expresses a chimeric antigen receptor (CAR). Example 84. The method of Example 83, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain. Example 85. The method of Example 84, wherein the antigen binding domain binds to a synthetic antigen. Example 86. The method of Example 85, wherein the synthetic antigen is the activator. Example 87. The method of Example 85, wherein the synthetic antigen is different than the activator. Example 88. The method of Example 84, wherein the antigen binding domain binds to an autoantigen. Example 89. The method of Example 88, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, Fortem Ref. No. DCT.010WO interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. Example 90. The method of Example 84, wherein the antigen binding domain binds to an antigen on an autoreactive inflammatory immune cell. Example 91. The method of Example 90, wherein the antigen is interleukin 23 receptor (IL23R) or CD83. Example 92. The method of any one of Examples 52 to 82, wherein the engineered Treg does not express any CAR. Example 93. The method of any one of Examples 52 to 92, further comprising administering an immune-activating agent to the subject, wherein the immune-activating agent comprises the activator coupled to a targeting moiety, and wherein the targeting moiety binds to a marker on a target cell. Example 94. The method of Example 93, wherein the targeting moiety comprises an antibody, an antibody fragment, a scFv, a nanobody, or a peptide. Example 95. The method of Example 93 or 94, wherein the marker is an autoantigen. Example 96. The method of Example 95, wherein the autoantigen is expressed by a healthy cell of a subject. Example 97. The method of Example 95 or 96, wherein the autoantigen is expressed by a cell of a transplanted organ or tissue of a subject. Example 98. The method of any one of Examples 95 to 97, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen. Example 99. The method of Example 93 or 94, wherein the marker is an antigen expressed by an autoreactive immune cell. Example 100. The method of Example 99, wherein the antigen is interleukin 23 receptor (IL23R) or CD83. Fortem Ref. No. DCT.010WO Example 101. The method of any one of Examples 52 to 100, wherein the disease or condition is an autoimmune disease. Example 102. The method of Example 101, wherein the autoimmune disease is Addison’s disease, amyotrophic lateral sclerosis (ALS), arthritis, asthma, autoimmune atrophic gastritis, autoimmune hemolytic anemia, autoimmune uveitis, chronic action hepatitis, diabetes, fibrotic disease Goodpasture syndrome, graft versus host disease (GvHD), Graves’ disease, Hashimoto’s thyroiditis, idiopathic thrombocytopenia, inflammatory bowel disease, inclusion body myositis, hemophilia, lupus, mixed connective tissue disease, multiple sclerosis (MS), myasthenia gravis, pemphigus, pernicious anemia, polymyositis, primary biliary cirrhosis, primary myxedema, psoriasis, scleroderma, Sjogren’s syndrome, sympathetic ophthalmia, or vitiligo. Example 103. The method of any one of Examples 52 to 100, wherein the disease or condition is organ or tissue transplantation. Conclusion Although many of the embodiments are described above with respect to compositions and methods for Treg immunotherapy, the technology is applicable to other applications and / or other approaches, such as immunotherapy using other types of immune cells. Moreover, other embodiments in addition to those described herein are within the scope of the technology. Additionally, several other embodiments of the technology can have different configurations, components, or procedures than those described herein. A person of ordinary skill in the art, therefore, will accordingly understand that the technology can have other embodiments with additional elements, or the technology can have other embodiments without several of the features shown and described above with reference to FIGS. 1–18. The descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Where the context permits, singular or plural terms may also include the plural or singular term, respectively. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments. Fortem Ref. No. DCT.010WO Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. As used herein, the phrase “and / or” as in “A and / or B” refers to A alone, B alone, and A and B. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. Additionally, the term "comprising" is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. As used herein, the terms “about” and “approximately,” in reference to a number, is used herein to include numbers that fall within a range of 10%, 5%, or 1% in either direction (greater than or less than) the number unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). As used herein, the term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, may refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN or other algorithms available to persons of skill) or by visual inspection. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared. For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. For purposes herein, percent identity and sequence similarity may be performed using the BLAST algorithm, which is described in Altschul et al. (J. Mol. Biol. 215:403-410 Fortem Ref. No. DCT.010WO (1990)). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. A composition can be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated. As used herein, the term “subject” broadly refers to any animal, including but not limited to, human and non-human animals (e.g., dogs, cats, cows, horses, sheep, pigs, poultry, fish, crustaceans, etc.). As used herein, the term “effective amount” refers to the amount of a composition sufficient to effect beneficial or desired results. An effective amount can be administered in one or more administrations, applications or dosages and is not intended to be limited to a particular formulation or administration route. As used herein, the term “therapeutically effective amount” is an amount that is effective to ameliorate a symptom of a disease. A therapeutically effective amount can be a “prophylactically effective amount” as prophylaxis can be considered therapy. As used herein, the terms “administration” and “administering” refer to the act of giving a drug, prodrug, or other agent, or therapeutic treatment to a subject or in vivo, in vitro, or ex vivo cells, tissues, and organs. Exemplary routes of administration to the human body can be through space under the arachnoid membrane of the brain or spinal cord (intrathecal), the eyes (ophthalmic), mouth (oral), skin (topical or transdermal), nose (nasal), lungs (inhalant), oral mucosa (buccal or lingual), ear, rectal, vaginal, by injection (e.g., intravenously, subcutaneously, intratumorally, intraperitoneally, etc.) and the like. As used herein, the term “treatment” means an approach to obtaining a beneficial or intended clinical result. The beneficial or intended clinical result can include alleviation of symptoms, a reduction in the severity of the disease, inhibiting an underlying cause of a disease or condition, steadying diseases in a non-advanced state, delaying the progress of a disease, and / or improvement or alleviation of disease conditions. As used herein, the term “pharmaceutical composition” refers to the combination of an active ingredient with a carrier, inert or active, making the composition especially suitable for therapeutic or diagnostic use in vitro, in vivo or ex vivo. Fortem Ref. No. DCT.010WO The terms “pharmaceutically acceptable” or “pharmacologically acceptable,” as used herein, refer to compositions that do not substantially produce adverse reactions, e.g., toxic, allergic, or immunological reactions, when administered to a subject. As used herein, the term “pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers including, but not limited to, phosphate buffered saline solution, water, emulsions (e.g., such as an oil / water or water / oil emulsions), glycerol, liquid polyethylene glycols, aprotic solvents such as dimethylsulfoxide, N-methylpyrrolidone and mixtures thereof, and various types of wetting agents, solubilizing agents, anti-oxidants, bulking agents, protein carriers such as albumins, any and all solvents, dispersion media, coatings, sodium lauryl sulfate, isotonic and absorption delaying agents, disintegrants (e.g., potato starch or sodium starch glycolate), and the like. The compositions also can include stabilizers and preservatives. For examples of carriers, stabilizers and adjuvants, see, e.g., Martin, Remington's Pharmaceutical Sciences, 21st Ed., Mack Publ. Co., Easton, Pa. (2005), incorporated herein by reference in its entirety. As used herein, the term “transfection” refers to any method for introducing a nucleic acid into a cell, including both viral and non-viral methods, and encompasses both transient and stable modifications. To the extent any materials incorporated herein by reference conflict with the present disclosure, the present disclosure controls. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

Claims

Fortem Ref. No. DCT.010WO CLAIMS What is claimed is:

1. A composition for immunotherapy, the composition comprising: an engineered regulatory T-cell (Treg), wherein the engineered Treg expresses a chimeric cytokine receptor (CCR) comprising: an activator binding domain configured to bind an activator, wherein the activator is an exogenous small molecule; a transmembrane domain; and an intracellular domain; wherein at least one of the transmembrane domain or the intracellular domain comprises or is derived from an interleukin 2 receptor (IL2R) domain.

2. The composition of claim 1, wherein the transmembrane domain comprises or is derived from a transmembrane domain of an interleukin 2 receptor subunit α (IL2Rα), an interleukin 2 receptor subunit β (IL2Rβ), or an interleukin 2 receptor subunit γ (IL2Rγ).

3. The composition of claim 1 or 2, wherein the transmembrane domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 13 – SEQ ID NO:

15.

4. The composition of any one of claims 1 to 3, wherein the transmembrane domain comprises a sequence of any one of SEQ ID NO: 13 – SEQ ID NO:

15.

5. The composition of any one of claims 1 to 4, wherein the intracellular domain comprises or is derived from an intracellular domain of an IL2Rα, an IL2Rβ, an IL2Rγ, a TGFβ receptor I subunit, or a TGFβ receptor II subunit.

6. The composition of any one of claims 1 to 5, wherein the intracellular domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%,Fortem Ref. No. DCT.010WO 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 10 – SEQ ID NO:

12.

7. The composition of any one of claims 1 to 6, wherein the intracellular domain comprises a sequence of any one of SEQ ID NO: 10 – SEQ ID NO:

12.

8. The composition of any one of claims 1 to 7, wherein binding of the activator to the activator binding domain causes one or more of the following: maintenance of a Treg phenotype, conversion to a Treg memory phenotype, maintenance or upregulation of immunosuppressive activity, increased Treg proliferation, or improved Treg survival.

9. The composition of any one of claims 1 to 8, wherein binding of the activator to the activator binding domain causes activation of a STAT5 signaling pathway.

10. The composition of any one of claims 1 to 9, wherein binding of the activator to the activator binding domain causes upregulation of one or more of the following: FOXP3, Helios, interleukin 10 (IL10), interleukin 35 (IL35), TGFβ, CTLA-4, PD-1, LAG3, or CCR7.

11. The composition of any one of claims 1 to 10, wherein the activator binding domain comprises a single-chain variable fragment (scFv).

12. The composition of any one of claims 1 to 11, wherein the activator binding domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO:

9.

13. The composition of any one of claims 1 to 12, wherein the activator binding domain comprises a sequence of SEQ ID NO:

9.

14. The composition of any one of claims 1 to 13, wherein the activator has a molecular weight less than or equal to 5 kDa, 4 kDa, 3 kDa, 2 kDa, 1 kDa, 500 Da, 200 Da, or 100 Da.Fortem Ref. No. DCT.010WO 15. The composition of any one of claims 1 to 14, wherein the activator is selected from the group consisting of fluorescein, fluorescein isothiocyanate (FITC), fluorescein 5- maleimide, fluorescein-5-carboxamide, fluorescein-6-carboxamide, 6-FAM phosphoramidite, topiramate hemisuccinate, creatine, acetaminophen, ketamine, propofol, lidocaine, ractopamine, salicylate, salicylic acid, sulfasalazine, dapsone, albendazole, ivermectin, levamisole, permethrin, pyrantel, thiabendazole, procainamide, sulfamethazine, amikacin, amoxicillin, ampicillin, cefazolin, cefuroxime, cephalexin, chloramphenicol, chloramphenicol, ciprofloxacin, clenbuterol, cloxacillin, colistin A, dicloxacillin, enrofloxacin, furaltadone, gentamicin, gentamicin, kanamycin, kanamycin, kincomycin, lincomycin, metronidazole, nafcillin, nalidixic acid, neomycin, neomycin, nitrofurazone, norfloxacin, ofloxacin, oxacillin, spectinomycin, streptomycin, streptomycin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadimidine, sulfametoxydiazine, sulfanilamide, trimethoprim, carbamazepine, ethosuximide, lamotrigine, primidone, cetirizine, chlorpheniramine, diphenhydramine, doxylamine, promethazine, sulfadimethoxine, benzothiazinone, butylated hydroxytoluene, tripelennamine, chlorpromazine, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, ribavirin, meprobamate, acebutolol, atenolol, penbutolol, warfarin, salmeterol, aflatoxin B1, tetraxetan (DOTA), 4-[(6-methylpyrazin-2-yl) oxy]benzoate (MPOB), biotin, melamine, methotrexate, amphetamine, diethylpropion, dextromethorphan, pseudoephedrine, dihydrochlorothiazide, hydrochlorothiazide, clonazepam, diazepam, nitrazepam, rhodamine B, fluorescent brightener Ksn, zearalenone, Sudan Red1, acetaminophen, acrylamide, benzoic acid, benzophenone, benzothiazine, mercaptobenzothiazole, erythrosine, Sudan, tartrazine, erythromycin, sirolimus, atropine, ethyl glucuronide, aflatoxin M1, methocarbamol, fentanyl, hydromorphone, morphine, remifentanil, tapentadol, tramadol, pregabalin, gabapentin, amitriptyline, desipramine, imipramine, nortriptyline, venlafaxine, dinitrophenyl, His-tag, PEG methoxy group, etodolac, ibuprofen, ketoprofen, meclofenamic acid, phenylbutazone, acetyl salicylic acid, acetamiprid, acetochlor, carbadazim, carbaryl, chlorothalonil, chlorpyrifos, fenpropathrin, imazalil, imidacloprid, parathion, abscisic acid, dibutyl phthalate, clonazepam, lorazepam, oxazepam, phenobarbital, secobarbital, zaleplon, zolpidem, trazodone, fluoxetine, fluvoxamine, cortisone, dexamethasone, dihydrotestosterone, fluocinolone, methylprednisolone, prednisolone, stanozolol, triamcinolone, mazindol, methamphetamine, methylphenidate, modafinil, chrysoidine, deoxynivalenol, fumonisin, microcystin Lr, ochratoxin, sterigmatocystin, T-2 toxin, sildenafil, tadalafil, scopolamine, florfenicol, pirlimycin, and sulfaquinoxaline.Fortem Ref. No. DCT.010WO 16. The composition of any one of claims 1 to 15, wherein the activator is fluorescein, a fluorescein derivative, or tetraxetan (DOTA).

17. The composition of claim 16, wherein the activator is the fluorescein derivative, and the fluorescein derivative is wherein the fluorescein derivative is fluorescein isothiocyanate (FITC), fluorescein 5-maleimide, fluorescein-5-carboxamide, fluorescein-6- carboxamide, or 6-FAM phosphoramidite.

18. The composition of any one of claims 1 to 17, wherein the CCR comprises: a first cytokine receptor chain comprising the activator binding domain, the transmembrane domain, and the intracellular domain, and a second cytokine receptor chain comprising: a second activator binding domain configured to bind the activator; a second transmembrane domain comprising or derived from an IL2R transmembrane domain; and a second intracellular domain comprising or derived from an IL2R intracellular domain.

19. The composition of claim 18, wherein: the transmembrane domain comprises or is derived from an IL2Rβ transmembrane domain, the intracellular domain comprises or is derived from an IL2Rβ intracellular domain, the second transmembrane domain comprises or is derived from an IL2Rγ transmembrane domain, and the second intracellular domain comprises or is derived from an IL2Rγ intracellular domain.

20. The composition of any one of claims 1 to 19, wherein the CCR comprises a hinge domain.

21. The composition of claim 20, wherein the hinge domain comprises or is derived from a hinge domain of a CD8, a CD3, a CD4, a CD28, a 4-1BB, a CD28, an OX40, an ICOS, a CD27, an immunoglobulin, or an EpoR.Fortem Ref. No. DCT.010WO 22. The composition of claim 20 or 21, wherein the hinge domain comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to SEQ ID NO:

22.

23. The composition of any one of claims 20 to 22, wherein the hinge domain comprises a sequence of SEQ ID NO:

22.

24. The composition of any one of claims 1 to 23, wherein the CCR comprises a signal peptide.

25. The composition of claim 24, wherein the signal peptide is comprises or is derived from a signal peptide of an IL2Rα, an IL2Rβ, anIL2Rγ, an interleukin 4 receptor subunit α (IL4Rα), an interleukin 7 receptor subunit α (IL7Rα), an interleukin 15 receptor subunit α (IL15Rα), an interleukin 21 receptor subunit α (IL21Rα), an interleukin 1 receptor (IL1R), a CD123, a CD124, an interleukin 5 receptor subunit α (IL5Rα), an interleukin 5 receptor subunit β (IL5Rβ), a CD126, a CD132, a CD129, an interleukin 11 receptor subunit α (IL11Rα), an interleukin 12 receptor subunit β1 (IL12Rβ1), an interleukin 12 receptor subunit β2 (IL12Rβ2), interleukin 13 receptor subunit α1 (IL13Rα1), a CD122, an interleukin 18 receptor (IL18R), an interleukin 23 receptor (IL23R), an interleukin 27 receptor subunit α (IL27Rα), a CD130, an immunoglobulin, a CD8, a CD28, or a GM-CSF.

26. The composition of claim 24 or 25, wherein the signal peptide comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 16 – SEQ ID NO:

21.

27. The composition of any one of claims 24 to 26, wherein the signal peptide comprises a sequence of any one of SEQ ID NO: 16 – SEQ ID NO:

21.

28. The composition of any one of claims 1 to 27, wherein the CCR comprises a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 1 – SEQ ID NO: 4.Fortem Ref. No. DCT.010WO 29. The composition of any one of claims 1 to 28, wherein the CCR comprises a sequence of any one of SEQ ID NO: 1 – SEQ ID NO:

4.

30. The composition of any one of claims 1 to 29, wherein the CCR is encoded by a sequence having at least 70%, 75%, 80%, 85%, 87%, 90%, 93%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to any one of SEQ ID NO: 5 – SEQ ID NO:

8.

31. The composition of any one of claims 1 to 30, wherein the CCR is encoded by a sequence of any one of SEQ ID NO: 5 – SEQ ID NO:

8.

32. The composition of any one of claims 1 to 31, wherein the engineered Treg expresses a chimeric antigen receptor (CAR).

33. The composition of claim 32, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain.

34. The composition of claim 33, wherein the antigen binding domain binds to a synthetic antigen.

35. The composition of claim 34, wherein the synthetic antigen is the activator.

36. The composition of claim 34, wherein the synthetic antigen is different than the activator.

37. The composition of claim 33, wherein the antigen binding domain binds to an autoantigen.

38. The composition of claim 37, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen.Fortem Ref. No. DCT.010WO 39. The composition of claim 33, wherein the antigen binding domain binds to an antigen on an autoreactive inflammatory immune cell.

40. The composition of claim 39, wherein the antigen is interleukin 23 receptor (IL23R) or CD83.

41. The composition of any one of claims 1 to 31, wherein the engineered Treg does not express any CAR.

42. A pharmaceutical composition comprising the composition of any one of claims 1 to 41 and a pharmaceutically acceptable carrier.

43. A system for immunotherapy, the system comprising: the composition of any one of claims 1 to 41 or the pharmaceutical composition of claim 42; and an immune-activating agent comprising the activator coupled to a targeting moiety, wherein the targeting moiety binds to a marker on a target cell.

44. The system of claim 43, wherein the targeting moiety comprises an antibody, an antibody fragment, a scFv, a nanobody, or a peptide.

45. The system of claim 43 or 44, wherein the marker is an autoantigen.

46. The system of claim 45, wherein the autoantigen is expressed by a healthy cell of a subject.

47. The system of claim 45 or 46, wherein the autoantigen is expressed by a cell of a transplanted organ or tissue of a subject.

48. The system of any one of claims 45 to 47, wherein the autoantigen is carcinoembryonic antigen (CEA), CD19, CD83, a citrullinated protein, a carbamylated protein, Factor VIII (FVIII), GAD65 beta-cell epitopes, ganglioside D3 (GD3), HiP2, HLA-Fortem Ref. No. DCT.010WO A2, insulin, interleukin 23 receptor (IL23R), myelin basic protein, myelin oligodendrocyte glycoprotein, 2,4,6-trinitrophenol (TNP), or type II collagen.

49. The system of claim 43 or 44, wherein the marker is an antigen expressed by an autoreactive immune cell.

50. The system of claim 49, wherein the antigen is interleukin 23 receptor (IL23R) or CD83.

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