Tissue-directed antibodies and methods of using the same

Abstract

Embodiments provided herein, provide for polypeptides, pharmaceutical compositions, and methods that can be used to target at least two types of cells to modulate the activity of the same to treat disorders, such as autoimmune disorders.

Description

[0001] DOCKET NO. ZAG-006WO PATENT

[0002] TISSUE-DIRECTED ANTIBODIES AND METHODS OF USING THE SAME

[0003] CROSS-REFERENCE TO RELATED APPLICATIONS

[0004] This application claims priority to U.S. Provisional Application No. 63 / 708,232, filed October 16, 2024, which is hereby incorporated by reference in its entirety. REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0005] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on October 16, 2025, is named “ZAG-006WO_SEQ.xml” and is 75,536 bytes in size.

[0006] FIELD

[0007] The embodiments provided herein relate to compositions that target different cells to regulate an immune response.

[0008] BACKGROUND

[0009] The thymus is the primary lymphoid organ responsible for T cell development and education. The development of T cells that bear the a(3 form of the T cell receptor occurs exclusively within the thymus. Intrathymic T cell maturation proceeds from fetal liver- or bone marrow-derived haematopoietic stem cells and occurs via a differentiation program readily characterized by changes to cell surface phenotype, proliferation status and functionality. Key events in T cell development include lineage commitment, selection events, and thymic emigration. Thymic epithelial cells (TECs) are a key component of the thymic stroma. TECs in the thymic cortex (cTECs) are specialized for T cell positive selection and ensure that mature T cells are self-MHC restricted. Medullary TECs (mTECs) or dendritic cells are involved in T cell negative selection wherein apoptosis is induced in T cells showing a high degree of self-avidity (Klein, L., Hinterberger, M., Wirnsberger, G., & Kyewski, B. (2009). Antigen presentation in the thymus for positive selection and central tolerance induction. Nature Reviews Immunology, 9(12), 833-844. https: / / doi.org / 10.1038 / nri2669; and Hinterberger, M., Aichinger, M., Prazeres da Costa, O., Voehringer, D., Hoffmann, R., & Klein, L. (2010). Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance. Nature Immunology, 11(6), 512-519. https: / / doi.org / 10.1038 / ni.1874; which are hereby incorporated by reference in their entirety). mTECs play a vital role in shaping the T cell repertoire by promoting the conversion of

[0010] -1-

[0011] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen-specific thymocytes into antigen-specific regulatory T cells (Tregs), which in turn suppress the immune response to self-antigens in peripheral tissues. mTECs achieve this by expressing and presenting tissue-specific antigens (TSAs) to developing thymocytes, leading to the selection of T cells that recognize these antigens as self. Thymocytes that recognize self-antigens with high affinity are either eliminated through negative selection or converted into Tregs through a process called agonist selection. The resulting antigen-specific Tregs migrate to the peripheral tissues, where they exert a bystander effect by suppressing immune responses to self-antigens, thereby maintaining self-tolerance and preventing autoimmune diseases. Thus, TEC -mediated selection promotes a self-tolerant and highly diverse T cell repertoire that can recognize foreign antigens presented by self-MHC molecules. Together, positive and negative selection provide a balance to create a broadly reactive T cell receptor repertoire with a low — but not absent — potential for self-reactivity. Regulation of self- reactive T cells is an especially attractive approach for the treatment of autoimmune diseases. The embodiments provided for herein fulfill these needs as well as others.

[0012] SUMMARY

[0013] In some embodiments, molecules for inducing antigen-specific thymic Tregs against an antigen of interest are provided, which can, for example be administered to a subject systemically. In some embodiments, the molecules comprise a thymic cell targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest.

[0014] In some embodiments, molecules comprising a cell targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest are provided. In some embodiments, the cell targeting domain binds to a thymic cell. In some embodiments, the cell targeting domain binds specifically to a thymic cell.

[0015] In some embodiments, provided herein is a molecule comprising a cell targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest, wherein the cell targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0016] In some embodiments, provided herein is a molecule for inducing tolerance against an antigen of interest, wherein the molecule comprises a cell targeting domain linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0017] In some embodiments, provided herein is a molecule for inducing antigen-specific Tregs against an antigen of interest, wherein the molecule comprises a cell targeting domain

[0018] -2-

[0019] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0020] In some embodiments, provided herein is a molecule for inducing antigen-specific Tregs against an antigen of interest, wherein the molecule comprises a cell targeting domain linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell, wherein the molecule does not significantly induce antigen-specific Teff cells.

[0021] In some embodiments, provided herein is a molecule comprising: a) a cell targeting domain that binds to cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, C-type lectin domain family 7 (CLEC7A), CD24, CD70, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), EGF like repeats and discoidin domains 3 (EDIL3), growth arrest-specific gene 6 (GAS6), T-cell membrane protein 4 (TIM4); b) an autoimmune, alloimmune, allergic, inflammatory, or anti-drug immune response associated antigen of interest; and c) optionally an Fc region, wherein the cell targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0022] In some embodiments, provided herein are pharmaceutical compositions comprising the same. In some embodiments, provided herein are methods of using the same.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS

[0024] FIG.1 illustrates non-limiting embodiments as provided for herein.

[0025] FIG.2A shows changes to population (shown as percentage CD4+FoxP3+ T cells of CD4+ T cells) of CD4+FoxP3+ T cells following treatment.

[0026] FIG.2B shows changes to population (shown as percentage of live CD4+ T cells) of CD4+ T cells following treatment.

[0027] FIG.3 shows changes to populations of CD4+ T cells and CD4+FoxP3+ T cells following treatment.

[0028] FIG.4A shows changes to population of CD4+FoxP3+ T cells following treatment.

[0029] FIG.4B shows changes to population of CD4+ T cells following treatment.

[0030] FIG.5A shows changes to population of CD4+FoxP3+ T cells following treatment.

[0031] -3-

[0032] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0033] FIG.5B shows changes to population of CD4+ T cells following treatment.

[0034] FIG.6 A shows changes to population of CD4+ T cells following treatment.

[0035] FIG.6B shows changes to population of CD4+FoxP3+ T cells following treatment.

[0036] FIG.7A shows changes to population of CD4+ T cells following treatment.

[0037] FIG.7B shows changes to population of CD4+FoxP3+ T cells following treatment.

[0038] FIG.8A shows changes to population of CD4+ T cells at days 3 and 10 following treatment.

[0039] FIG.8B shows changes to population of CD4+FoxP3+ T cells at days 3 and 10 following treatment.

[0040] FIG.9 A shows changes to EAE score following treatment.

[0041] FIG.9B shows changes to EAE score following treatment.

[0042] FIG.10A shows changes to population of CD4+ T cells following treatment.

[0043] FIG. 1 OB shows changes to population of CD4+FoxP3+ T cells following treatment.

[0044] FIG. 10C shows changes to absolute numbers (shown as total number of CD4+ T cells) of CD4+ T cells following treatment.

[0045] FIG.10D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0046] FIG.l 1A shows changes to population of CD4+FoxP3+ T cells following treatment.

[0047] FIG.1 IB shows changes to population of CD4+FoxP3+CD73- T cells following treatment.

[0048] FIG.l 1C shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0049] FIG.l ID shows changes to absolute numbers of CD4+FoxP3+CD73- T cells following treatment.

[0050] FIG.12A shows changes to population of CD4+ T cells following treatment.

[0051] FIG.12B shows changes to population of CD4+FoxP3+ T cells following treatment.

[0052] FIG.12C shows changes to absolute numbers of CD4+ T cells following treatment.

[0053] FIG.l 2D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0054] FIG.13 A shows changes to population of CD4+ T cells following treatment.

[0055] -4-

[0056] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0057] FIG.13B shows changes to absolute numbers of CD4+ T cells following treatment.

[0058] FIG. 13C shows changes to population of CD4+FoxP3+ T cells following treatment.

[0059] FIG. 13D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0060] FIG.13E shows changes to population of CD4+FoxP3+CD73- T cells following treatment.

[0061] FIG.13F shows changes to absolute numbers of CD4+FoxP3+ CD73- T cells following treatment.

[0062] FIG.14A shows changes to population of CD4+ T cells following treatment.

[0063] FIG.14B shows changes to population of CD4+FoxP3+ T cells following treatment.

[0064] FIG.14C shows changes to absolute numbers of CD4+ T cells following treatment.

[0065] FIG.14D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0066] FIG.15A shows changes to population of CD4+ T cells following treatment.

[0067] FIG. 15B shows changes to absolute numbers of CD4+ T cells following treatment.

[0068] FIG.15C shows changes to population of CD4+FoxP3+ T cells following treatment.

[0069] FIG. 15D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0070] FIG.15E shows changes to population of CD4+FoxP3+CD73- T cells following treatment.

[0071] FIG.15F shows changes to absolute numbers of CD4+FoxP3+CD73- T cells following treatment.

[0072] FIG.16A shows changes to population of CD4+ T cells following treatment.

[0073] FIG.16B shows changes to population of CD4+FoxP3+ T cells following treatment.

[0074] FIG.16C shows changes to absolute numbers of CD4+ T cells following treatment.

[0075] FIG.16D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0076] FIG.17A shows changes to population of CD4+ T cells following treatment.

[0077] FIG.17B shows changes to absolute numbers of CD4+ T cells following treatment.

[0078] FIG.17C shows changes to population of CD4+FoxP3+ T cells following treatment.

[0079] FIG.17D shows changes to absolute numbers of CD4+FoxP3+ T cells following treatment.

[0080] -5-

[0081] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0082] FIG.17E shows changes to population of CD4+FoxP3+CD73- T cells following treatment.

[0083] FIG.17F shows changes to absolute numbers of CD4+FoxP3+CD73- T cells following treatment.

[0084] FIG.18A shows changes to EAE score following treatment.

[0085] FIG.18B shows changes to EAE score following treatment.

[0086] FIG.19A shows changes to EAE score following treatment.

[0087] FIG.19B shows changes to EAE score following treatment.

[0088] FIG.19C shows changes to EAE score following treatment.

[0089] FIG.20A shows changes to EAE score (upper panel) and EAE onset (lower panel) following treatment at a dose of 1 pg.

[0090] FIG.20B shows changes to EAE score (upper panel) and EAE onset (lower panel) following treatment at a dose of 0.1 pg.

[0091] FIG.21 A shows changes to population of Tconv cells following treatment.

[0092] FIG.21B shows changes to population of FoxP3lowTreg progenitor cells following treatment.

[0093] FIG.21C shows changes to population of non-recirculating Treg cells following treatment.

[0094] FIG.21D shows changes to population of total Treg cells following treatment.

[0095] FIG.21E shows changes to population of Treg / Tconv cells following treatment.

[0096] FIG.22 shows reduced IFNy levels following treatment.

[0097] FIG.23 shows reduced IFNy levels following treatment.

[0098] FIG.24A shows that a single dose of the test article was sufficient to mitigate disease.

[0099] FIG.24B shows that a single dose of the test article was sufficient to mitigate disease.

[0100] FIG.24C shows that weekly dosing of the test article was sufficient to mitigate disease.

[0101] FIG.24D shows that weekly dosing of the test article was sufficient to mitigate disease.

[0102] DETAILED DESCRIPTION

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[0104] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0105] As used herein and unless otherwise indicated, the term “about” means that the numerical value is approximate and small variations would not significantly affect the practice of the disclosed embodiment. Where a numerical limitation is used, unless indicated otherwise by the context, “about” means the numerical value can vary by ±10% and remain within the scope of the disclosed embodiments.

[0106] As used herein and in the appended claims, the singular forms “a”, “an” and “the” include plural reference unless the context clearly dictates otherwise.

[0107] As used herein, the term “animal” includes, but is not limited to, humans and nonhuman vertebrates such as wild, domestic, and farm animals. Accordingly, as used herein, the term “mammal” means a rodent (i.e., a mouse, a rat, or a guinea pig), a monkey, a cat, a dog, a cow, a horse, a pig, or a human. In some embodiments, the mammal is a human.

[0108] As used herein, the term “antigen” refers to any molecule that the immune system can recognize and respond to. In some embodiments, antigen refers to an antigen of interest, such as a polypeptide, a molecule, a substance, an antibody, a ligand, a payload, or similar.

[0109] As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” a therapeutic compound with an individual or patient or cell includes the administration of the compound or composition to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing target.

[0110] As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any composition or method that recites the term “comprising” should also be understood to also describe such compositions as consisting, consisting of, or consisting essentially of the recited components or elements.

[0111] As used herein, the term “individual,” “subject,” or “patient,” which can be used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans.

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[0113] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0114] As used herein, the term “inhibit” refers to a result, symptom, or activity being reduced as compared to the activity or result in the absence of the compound that is inhibiting the result, symptom, or activity. In some embodiments, the result, symptom, or activity, is inhibited by about, or, at least, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99%. A result, symptom, or activity can also be inhibited if it is completely eliminated or extinguished.

[0115] As used herein, the phrase “in need thereof’ means that the subject has been identified as having a need for the particular method or treatment. In some embodiments, the identification can be by any means of diagnosis. In any of the methods and treatments described herein, the subject can be in need thereof. In some embodiments, the subject is in an environment or will be traveling to an environment in which a particular disease, disorder, or condition is prevalent.

[0116] As used herein, the phrase “integer from X to Y” means any integer that includes the endpoints. For example, the phrase “integer from 1 to 5” means 1, 2, 3, 4, or 5.

[0117] As used herein, the phrase “self-antigen” refers to any polypeptide, protein or molecule that is produced by a subject’s own body and is typically recognized as "self" by the immune system. A “self-antigen” can also refer to as a tissue antigen, and means a polypeptide, protein or molecule that is produced by an individual's own body and is present within or on the surface of the cells of a specific tissue or organ. These tissue antigens are recognized as "self" by the immune system and are typically tolerated without provoking an immune response.

[0118] "Specific binding" or "specifically binds to" or is "specific for" a particular antigen, target, or an epitope means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

[0119] Specific binding for a particular antigen, target, or an epitope can be exhibited, for example, by an antibody, or the antigen-binding fragment thereof, having a KD for an antigen or epitope of at least about 10-4M, at least about 10-5M, at least about 10’6M, at least about 10’7M, at least about 10sM, at least about 10’9M, alternatively at least about 1010M, at least about 10‘nM, at least about 1012M, or lesser, where KD refers to the equilibrium dissociation

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[0121] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT constant of a particular antibody, or the antigen-binding fragment thereof, -target interaction. Typically, an antibody, or the antigen-binding fragment thereof, that specifically binds an antigen or target will have a KD that is, or at least, 2-, 4-, 5-, 10-, 20-, 50-, 100-, 500-, 1000-, 5,000-, 10,000-, or more times greater for a control molecule relative to the antigen or epitope.

[0122] In some embodiments, specific binding for a particular antigen, target, or an epitope can be exhibited, for example, by an antibody, or the antigen-binding fragment thereof, having a KA for a target, antigen, or epitope of at least 2-, 4-, 5-, 20-, 50-, 100-, 500-, 1000-, 5,000-, 10,000- or more times greater for the target, antigen, or epitope relative to a control, where KA refers to the equilibrium association constant of a particular antibody, or the antigen-binding fragment thereof, -antigen interaction.

[0123] As provided herein, the compounds and compositions provided for herein can be used in methods of treatment as provided herein. As used herein, the terms “treat,” “treated,” or “treating” mean both therapeutic treatment and prophylactic measures wherein the object is to slow down (lessen) an undesired physiological condition, disorder or disease, or obtain beneficial or desired clinical results. For purposes of these embodiments, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of extent of condition, disorder or disease; stabilized (i.e., not worsening) state of condition, disorder or disease; delay in onset or slowing of condition, disorder or disease progression; amelioration of the condition, disorder or disease state or remission (whether partial or total), whether detectable or undetectable; an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or improvement of condition, disorder or disease. Treatment includes eliciting a clinically significant response without excessive levels of side effects. Treatment also includes prolonging survival, as applicable for a specific disease, as compared to expected survival if not receiving treatment. Thus, “treatment of an autoimmune condition” or “treating autoimmunity” means an activity that alleviates or ameliorates any of the primary phenomena or secondary symptoms associated with the autoimmune condition other condition described herein when the terms “treat,” “treated,” or “treating" are used in conjunction with such condition.

[0124] As used herein, the term “thymic cells” refers to cells that ordinarily form part of, or are located in, the thymus, including, but not limited to, those listed in Table 1. Within the general category of thymic cells are both thymic stromal cells and cells of hematopoietic

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[0126] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT origin (such as T cell progenitors, immature T cells, and mature T cells) that reside within the thymus for at least some period of time — for example as part of the T cell maturation and T cell education processes that occur within the thymus.

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[0128] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0129] In some embodiments, the thymic cell is a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, junction thymic epithelial cell (jTEC), thymic progenitor epithelial cell (TPEC), proliferating TPEC, thymic epithelial cell (TEC), proliferating TEC, cortical thymic epithelial cell (cTEC), proliferating cTEC, or proliferating mTEC.

[0130] Non-limiting examples of mimetic mTEC include, but are not limited to, basal (skin / lung) mTEC, enterocyte / hepatocyte mTEC, ciliated mTEC, ionocyte mTEC, keratinocyte mTEC, microfold mTEC, muscle mTEC, neuroendocrine mTEC, parathyroid mTEC, secretory mTEC, thyroid mTEC, and tuft mTEC. In some embodiments, the mimetic mTEC is a basal (skin / lung) mTEC. In some embodiments, the mimetic mTEC is an enterocyte / hepatocyte mTEC. In some embodiments, the mimetic mTEC is a ciliated mTEC. In some embodiments, the mimetic mTEC is an ionocyte mTEC. In some embodiments, the mimetic mTEC is a keratinocyte mTEc. In some embodiments, the mimetic mTEC is a microfold mTEC. In some embodiments, the mimetic mTEC is a muscle mTEC. In some embodiments, the mimetic mTEC is a neuroendocrine mTEC. In some embodiments, the mimetic mTEC is a parathyroid mTEC. In some embodiments, the mimetic mTEC is a secretory mTEC. In some embodiments, the mimetic mTEC is a thyroid mTEC. In some embodiments, the mimetic mTEC is a tuft mTEC.

[0131] In some embodiments, the basal (skin / lung) mTEC is a mimetic cell resembling basal cells of the skin and lung that putatively give rise, as in the periphery, to more terminally differentiated mimetic cells, such as keratinocyte mTECs and secretory / ionocyte mTECs.

[0132] In some embodiments, the enterocyte / hepatocyte mTEC is a Hnf4a+ Hnf4g+ mimetic cell expressing transcripts associated with gut enterocytes and liver hepatocytes, such as Vill, Aldob, and Apoa4. These cells putatively give rise to microfold mTECs (Michelson DA,

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[0134] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0135] Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0136] In some embodiments, the ciliated mTEC is a Foxjl-i- Rfx2+ Trp73+ mimetic cell exhibiting polarized cilia, line respiratory cysts in the thymus, and express transcripts associated with ciliated cells, such as Dynlrb2, Pifo, and Tubb4b. Without wishing to be bound to a particular theory, expression of a model antigen in ciliated mTECs is sufficient to induce cognate T cell tolerance (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0137] In some embodiments, the ionocyte mTEC is a Foxil-i- Foxi2+ mimetic cell expressing transcripts (Cftr, Slcl2a2, Atp6vlbl) associated with ionocytes, and ion channel rich cells found in the kidney and lung epithelium (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0138] In some embodiments, the keratinocyte mTEC is a Grhll-i- mimetic cell morphologically resembling skin keratinocytes, producing microscopically detectable KrtlO-i- cornified bodies that in humans are known as Hassall’s corpuscles (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0139] In some embodiments, the microfold mTEC is a Spib-i- Sox8+ mimetic cell morphologically resembling Peyer’s patch microfold cells, with dendritic processes and an associated ‘lymphocyte pocket’ (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0140] In some embodiments, the muscle mTEC is a Myog-i- mimetic cell morphologically resembling and expressing transcripts (Ckm, Des, Myll) associated with skeletal muscle. Without wishing to be bound to a particular theory, expression of a model antigen in muscle mTECs is sufficient to induce cognate T cell tolerance (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0141] In some embodiments, the neuroendocrine mTEC is a Foxa2+ Foxa3+ Insml-i- Ascll+ mimetic cell expressing transcripts encoding neuroendocrine markers (Scg5, Snap25, Chga, Stxbp51) and possessing abundant secretory granules. Under the umbrella of neuroendocrine mTECs, further heterogeneity exists including Ptfla+ pancreatic-like, Cdx2+ enteroendocrine-like, Pax6+, and Soxl 1+ subsets (Michelson DA, Mathis D, Thymic

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[0143] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0144] In some embodiments, the parathyroid mTEC is a Gcm2+ mimetic cell expressing microscopically detectable parathyroid hormone (PTH) (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0145] In some embodiments, the secretory mTEC is a Foxal-i- Spdef-i- mimetic cell expressing transcripts (Gabrp, Aqp4, Scgb3a2, Sftpd, Muc5ac, Muc5b) associated with mixed secretory cell types, including goblet cells, club cells, and alveolar epithelial cells (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0146] In some embodiments, the thyroid mTEC is a mimetic cell identified as thyroglobulin- and calcitonin- expressing cell (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0147] In some embodiments, the tuft mTEC is a Pou2f3+ mimetic cell expressing markers of tuft cells (IL-25, ChAT, Dclkl); mediate tolerance to tuff cell-restricted antigens and control the accumulation of type 2 ILCs and NKT cells in the thymus (Michelson DA, Mathis D, Thymic mimetic cells: tolerogenic masqueraders, Trends in Immunology, October 2022, Vol. 43, No. 10).

[0148] Medullary thymic epithelial cells (mTECs) ectopically express a plethora of peripheral -tissue antigens (PTAs), which drive deletion or phenotypic diversion of self- reactive immature T cells during thymic differentiation (Michelson DA, et al., Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells, 2022, Cell 185, 1-17). Failure of PTA expression causes multiorgan autoimmunity. T cells undergo positive selection to ensure capability to bind to MHC complexes. In this process, cells in the thymus display short peptides, on their own MHC class I and class II molecules, allowing immature T cells to bind. If T cell receptors (TCRs) are incapable of binding to the antigen, the T cell undergoes apoptosis. If the TCR successfully binds to the MHC complexes on the thymic cells, the T cell receives survival signals and is thus positively selected. Further, this positive selection process also determines if a T cell will become a CD8+ T cell or a CD4+ T cell. Without wishing to be bound by a particular theory, if a TCR complex binds strongly to MHC class II, the complex will send intracellular signals to induce the expression of a protein called ThPOK. This protein reduces the expression of another key protein, called Runx3, responsible for driving CD8 expression. Because low Runx3 causes

[0149] -13-

[0150] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT low CD8, these ThPOK+, Runx3- cells become CD4+. If, however, a developing T cell does not bind strongly to MHC class II, ThPOK levels will be low and thus Runx3 levels will be high, pushing the T cell to differentiate into a CD8+ cell.

[0151] Without wishing to be bound by a particular theory, there are two basic classes of MHC molecules in mammals, MHC class I and MHC class II. Both classes are large protein complexes formed by the association of two separate proteins. Each class includes transmembrane domains that anchor the complex into the cell membrane. MHC class 1 molecules are formed from two non-covalently associated proteins, the a chain and 02- microglobulin. The a chain comprises three distinct domains, al, a2 and a3. The three- dimensional structure of the al and a2 domains forms the groove into which antigen fits for presentation to T cells. The a3 domain is an Ig-fold like domain that contains a transmembrane sequence that anchors the a chain into the cell membrane of the antigen presenting cell (APC). MHC class I complexes, when associated with antigen (and in the presence of appropriate co-stimulatory signals) stimulate CD8 cytotoxic T cells, which function to kill any cell which they specifically recognize. The two proteins which associate non-covalently to form MHC class II molecules are termed the a and 0 chains. The a chain comprises al and a2 domains, and the 0 chain comprises 01 and 02 domains. The cleft into which the antigen fits is formed by the interaction of the al and 01 domains. The a2 and 02 domains are transmembrane Ig-fold like domains that anchor the a and 0 chains into the cell membrane of the APC. MHC class II complexes, when associated with antigen (and in the presence of appropriate co-stimulatory signals) stimulate CD4 T cells. The primary functions of CD4 T cells are to initiate the inflammatory response, to regulate other cells in the immune system, and to provide help to B cells for antibody, or the antigen-binding fragment thereof, synthesis.

[0152] In humans, MHC molecules (with the exception of class I 02-microglobulin) are encoded by the HLA region, which is located on chromosome 6 and constitutes over 100 genes. There are 3 class I MHC a chain protein loci, termed HLA- A, -B and -C. There are also 3 pairs of class II MHC a and 0 chain loci, termed HLA-DR (A and B), HLA-DP (A and B), and HLA-DQ (A and B). In rats, the class I a gene is termed RT1.A, while the class II genes are termed RT1.B a and RT1.B 0. The key role that MHC complexes play in triggering immune recognition has led to the development of methods by which these complexes are used to modulate the immune response. For example, activated T cells which recognize “self’ antigens (autoantigens) are known to play a key role in autoimmune diseases (such as rheumatoid arthritis) and neurodegenerative diseases of autoimmune etiology (such as

[0153] -14-

[0154] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT multiple sclerosis). Building on the observation that isolated MHC class II molecules (loaded with the appropriate antigen) can substitute for APCs carrying the MHC class II complex and can bind to antigen-specific T cells, a number of researchers have proposed that isolated MHC / antigen complexes may be used to treat autoimmune disorders. Thus U.S. Pat. Nos. 5,194,425, and 5,284,935, each of which is hereby incorporated by reference in its entirety, disclose the use of isolated MHC class II complexes loaded with a specified autoantigen and conjugated to a toxin to eliminate T cells that are specifically immunoreactive with autoantigens.

[0155] MHC Class II antigens (or “MHC II antigens”) are major histocompatibility antigens, which are expressed on the surface of antigen-presenting cells, including dendritic cells, macrophages, B lymphocytes and certain epithelial cell types (e.g. cortical and medullary thymic epithelial cells). MHC molecules are essential for the presentation of antigenic peptides to CD4 T lymphocytes. Their expression is up-regulated on activated antigen- presenting cells. In certain contexts (e.g. an inflammatory context), MHC Class II is expressed by other cell types (e.g. endothelial cells, islet beta cells) that do not usually express MHC Class II. MHC Class II is expressed on the cell surface as a heterodimer consisting of an alpha chain and a beta chain. The tertiary structure of the molecule is such that a peptide-binding ‘groove’ or ‘cleft’ is formed between the al and pi domains of the alpha and beta chains respectively. The region of the groove is highly polymorphic, resulting in a high degree of allelic variation between MHC Class II molecules within outbred populations. Conventionally, peptides presented by MHC Class II are derived from extracellular proteins, which have been endocytosed by the cell, and are usually at least around 15 amino acids in length. It is within the endocytic compartment of a cell that the peptides are loaded into the groove, forming an MHC-peptide complex, which is subsequently transported to the cell surface. The MHC-peptide complex is recognized by a T cell receptor on the surface of a T lymphocyte. In humans, MHC Class II antigens are also called Human Leukocyte Antigens (HLA), examples of which are HLA-DM, HLA-DO, HLA-DP, HLA-DQ and HLA-DR. Examples of MHC Class II antigens in inbred laboratory mouse strains are IA and IE. Developing T cells in the thymus are presented with peptides bound to MHC molecules, to which they may be able to bind. While a moderate degree of binding leads to survival and positive selection, TCRs that bind too strongly to these MHC complexes are destined for the opposite fate. When TCRs bind with high enough affinity to the MHC complexes in the thymus, the intracellular signaling is so strong that it leads to cell death, thereby eradicating immature T cells that have a high likelihood of being self-reactive

[0156] -15-

[0157] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT and attacking our own cells. mTECs are uniquely important effectors of negative selection because they ectopically express thousands of peripheral tissue antigens (PTAs) in a mosaic fashion, allowing immature T cells to broadly sample self-antigens prior to their release into the periphery, promoting deletion of autoreactive T cell clones or their conversion into regulatory T cells (Tregs), and thereby preventing autoimmunity.

[0158] In some embodiments, the molecule binds to one or more cells. In some embodiments, the molecule binds to one or more thymic cells. In some embodiments, the molecule binds to at least one thymic cells. In some embodiments, the one or more, or at least one thymic cell is a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, junction thymic epithelial cell (jTEC), thymic progenitor epithelial cell (TPEC), proliferating TPEC, thymic epithelial cell (TEC), proliferating TEC, cortical thymic epithelial cell (cTEC), proliferating cTEC, or proliferating mTEC. In some embodiments, the molecule binds to a thymic cell and at least one more cell. In some embodiments, the molecule binds to a thymic cell and a dendritic cell.

[0159] In some embodiments, the molecule binds to a first thymic cells, and a second thymic cell. In some embodiments, the first thymic cell is selected from a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, junction thymic epithelial cell (jTEC), thymic progenitor epithelial cell (TPEC), proliferating TPEC, thymic epithelial cell (TEC), proliferating TEC, cortical thymic epithelial cell (cTEC), proliferating cTEC, or proliferating mTEC; and the second thymic cell is selected from a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, junction thymic epithelial cell (jTEC), thymic progenitor epithelial cell (TPEC), proliferating TPEC, thymic epithelial cell (TEC), proliferating TEC, cortical thymic epithelial cell (cTEC), proliferating cTEC, or proliferating mTEC. In some embodiments, the molecule binds to a thymic cell and at least one more cell. In some embodiments, the molecule binds to a splenic cell. In some embodiments, the molecule binds to a dendritic cell. In some embodiments, the molecule binds to a B cell. In some embodiments, the molecule binds to a thymic cell and a dendritic cell. In some embodiments, the molecule binds to a thymic cell, splenic cell, dendritic cell, and / or B cell. In some embodiments, the molecule binds to a thymic cell, a dendritic cell, and / or a B cell.

[0160] Provided herein are polypeptides, and molecules, e.g., that can be used as therapeutics that include 1 or 2 cell targeting domains that bind to at least 1 receptor on the surface of a

[0161] -16-

[0162] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thymic cell, such as an epithelial thymic cell; and 1 or 2 antigens of interest. In some embodiments, the compound comprises 1 or 2 antigens of interest, such as an antibody, or the antigen-binding fragment thereof, an antigen, a payload, or a fragment thereof. In some embodiments, the compound binds to at least 1 cell surface receptor molecule. In some embodiments, the compound binds to 2 different cell surface receptor molecules. In some embodiments, the compound binds to 2 cell surface receptor molecules, wherein said cell surface receptor molecules are of the same type. In some embodiments, the compound can comprise at least 1 antigen of interest. In some embodiments, the compound can comprise 2 antigens of interest. In some embodiments, the antigen of interest is an antibody, or the antigen-binding fragment thereof, an antigen, a payload, or a fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is bound to an antigen.

[0163] As used herein, the term “cell targeting domain” refers to a polypeptide, such as an antibody, or the antigen-binding fragment thereof, that binds to a receptor present on the surface of a thymic cell. In some embodiments, the cell targeting domain binds to a receptor on the surface of the thymic cell. In some embodiments, non-limiting examples of thymic cells include, but are not limited to, medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, junction thymic epithelial cell (jTEC), thymic progenitor epithelial cell (TPEC), proliferating TPEC, thymic epithelial cell (TEC), proliferating TEC, cortical thymic epithelial cell (cTEC), proliferating cTEC, or proliferating mTEC. In some embodiments, the thymic cell is a mTEC. In some embodiments, the thymic cell is a mimetic mTEC. In some embodiments, the thymic cell is an AIRE+ mTEC. In some embodiments, the thymic cell is an AIRE- mTEC. In some embodiments, the thymic cell is a mTEC progenitor cell. In some embodiments, the thymic cell is a mimetic mTEC progenitor cell. In some embodiments, the thymic cell is a basal (skin / lung) mTEC. In some embodiments, the thymic cell is an enterocyte / hepatocyte mTEC. In some embodiments, the thymic cell is a ciliated mTEC. In some embodiments, the thymic cell is an ionocyte mTEC. In some embodiments, the thymic cell is a keratinocyte mTEC. In some embodiments, the thymic cell is a microfold mTEC. In some embodiments, the thymic cell is a muscle mTEC. In some embodiments, the thymic cell is a neuroendocrine mTEC. In some embodiments, the thymic cell is a parathyroid mTEC. In some embodiments, the thymic cell is a secretory mTEC. In some embodiments, the thymic cell is a thyroid mTEC. In some embodiments, the thymic cell is a tuft mTEC.

[0164] In some embodiments, the molecule comprises one or more cell targeting domains. In some embodiments, the molecule comprises 1, or 2 cell targeting domains. In some

[0165] -17-

[0166] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT embodiments, the cell targeting domains bind to the same cell receptor. In some embodiments, the cell targeting domains bind to different cell receptors. For example, if the molecule comprises two cell targeting domains that bind to different cell receptors, the first cell targeting domain can bind to a first cell receptor and the second cell targeting domain can bind to a second cell receptor that is different from the first. In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is a Fab format antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is a scFv antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is an antibody, or the antigen-binding fragment thereof, as provided for herein.

[0167] In some embodiments, provided herein is a molecule comprising a cell targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest, wherein the cell targeting domain binds to a thymic cell.

[0168] In some embodiments, provided herein is a molecule comprising a cell targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest, wherein the cell targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0169] In some embodiments, provided herein is a molecule for inducing tolerance against an antigen of interest, wherein the molecule comprises a cell targeting domain linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0170] In some embodiments, provided herein is a molecule for inducing antigen-specific Tregs against an antigen of interest, wherein the molecule comprises a cell targeting domain linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0171] In some embodiments, provided herein is a molecule for inducing antigen-specific Tregs against an antigen of interest, wherein the molecule comprises a cell targeting domain linked to the antigen of interest or a domain that binds to the antigen of interest, wherein the targeting domain binds to a thymic cell, a splenic cell, a dendritic cell, or a B cell, wherein the molecule does not significantly induce antigen-specific Teff cells.

[0172] In some embodiments, provided herein is a molecule for inducing antigen-specific thymic Treg cells by systemic administration, wherein the molecule comprises a thymic cell

[0173] -18-

[0174] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT targeting domain linked to an antigen of interest or a domain that binds to the antigen of interest.

[0175] Without wishing to be bound to any particular theory, targeted delivery of an antigen to thymic epithelial cells (TECs) is a strategy aimed at facilitating antigen uptake, processing, and presentation on the cell surface, ultimately promoting antigen-specific T cell selection. Once the targeted antigen reaches the TECs, it is internalized through various endocytic mechanisms, including, but not limited to, receptor-mediated endocytosis, phagocytosis, or macropinocytosis. After internalization, the antigen is transported to endosomal or lysosomal compartments within the TECs, where it undergoes proteolytic processing. This processing generates antigenic peptides, or fragment thereof, that can bind to major histocompatibility complex (MHC) molecules. The generated antigenic peptides, or fragment thereof, are loaded onto MHC molecules within specialized compartments, such as the endoplasmic reticulum for MHC class I or endosomal compartments for MHC class II. Once the peptide-MHC complex is formed, it is transported to the TEC surface and presented to developing thymocytes. TECs expressing MHC class I molecules present the peptides to CD8+ T cells, while those expressing MHC class II molecules present the peptides to CD4+ T cells. The interaction between the peptide-MHC complex on TECs and the T cell receptor (TCR) on developing thymocytes drives the selection of T cells with appropriate antigen specificity. Thymocytes with low or intermediate affinity for self-antigens undergo positive selection, ensuring the survival of T cells capable of recognizing antigens in the context of self-MHC. Thymocytes with high affinity for self-antigens undergo negative selection, either being eliminated through apoptosis or diverted into regulatory T cell (Treg) differentiation to maintain self-tolerance (Klein, L., Hinterberger, M., Wirnsberger, G., & Kyewski, B. (2009). Antigen presentation in the thymus for positive selection and central tolerance induction. Nature Reviews Immunology, 9(12), 833-844. https: / / doi.org / 10.1038 / nri2669; Mathis, D., & Benoist, C. (2009). Aire. Annual Review of Immunology, 27, 287-312. https: / / doi”dot'’org / 10”dot'’1146 / annurev”dot'’immunol”dot”25”dot”022106'’dot”141532; Takaba, H., & Takayanagi, H. (2017). The Mechanisms of T Cell Selection in the Thymus. Trends in Immunology, 38(11), 805-816. https: / / doi“dot”org / 10“dot”1016 / j“dot”it“dot”2017“dot”08“dot”012; Starr, T. K., Jameson, S. C., & Hogquist, K. A. (2003). Positive and negative selection of T cells. Annual Review of Immunology, 21, 139-176. https : / / doi“dot”org / 10“dot” 1146 / annurev“dot”immunol“dot”21 “dot’T 20601 “dot” 141107 ;Roche, P. A., & Furuta, K. (2015). The ins and outs of MHC class Il-mediated antigen

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[0177] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT processing and presentation. Nature Reviews Immunology, 15(4), 203-216. https: / / doi“dot”org / 10“dot”1038 / nri3818; and Neefjes, J., Jongsma, M. L., Paul, P., & Bakke, O. (2011). Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nature Reviews Immunology, 11(12), 823-836. https: / / doi“dot”org / 10“dot'T038 / nri3084; each of which are hereby incorporated by reference in its entirety).

[0178] In some embodiments, the molecule binds to a cell receptor. In some embodiments, the molecule binds to a thymic cell receptor. In some embodiments, the cell receptor is expressed on the surface of the cell. In some embodiments, the cell receptor is expressed on the surface of the thymic cell. In some embodiments, the cell receptor is expressed on the surface of an exosome. In some embodiments, the receptor is expressed on the surface of a thymic-derived exosome. Without wishing to be bound to any particular theory, thymic- derived exosomes are small, membrane -bound vesicles released by thymic cells, carrying various biological molecules like proteins, lipids, and nucleic acids. These exosomes can interact with B cells via surface receptors, such as those provided herein (Thery, C., Ostrowski, M., & Segura, E. (2009). Membrane vesicles as conveyors of immune responses. Nature Reviews Immunology, 9(8), 581-593. https: / / doi“dot”org / 10“dot”1038 / nri2567; which is hereby incorporated by reference in its entirety). B cells can uptake thymic-derived exosomes through endocytosis. Upon interaction, B cells internalize the exosomes by forming an invagination on their plasma membrane, which engulfs the exosome and forms a vesicle called an endosome within the B cell. Inside the B cell, the exosomal contents are released and can influence B cell function, differentiation, and interaction with other immune cells, ultimately contributing to immune regulation and response. B cell-induced tolerance is an essential mechanism by which the immune system prevents autoimmunity and maintains self-tolerance. B cells, as part of the adaptive immune response, produce antibodies that recognize and neutralize foreign antigens. However, they must also avoid reacting to selfantigens to prevent autoimmune reactions. Through a series of tightly regulated selection processes, including central and peripheral tolerance mechanisms, self-reactive B cells are either removed, rendered unresponsive, or undergo receptor editing to change their antigen specificity. By controlling these processes, the immune system ensures that B cells contribute to an effective defense against pathogens while minimizing the risk of autoimmunity and maintaining self-tolerance.

[0179] In some embodiments, the molecule that binds to the cell receptor comprises a native ligand. In some embodiments, the cell targeting domain that binds to the cell receptor

[0180] -20-

[0181] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT comprises a native ligand. In some embodiments, the ligand is a native soluble ligand, or a fragment thereof. In some embodiments, the ligand is a fragment of a native membrane- tethered ligand, or a fragment thereof. In some embodiments, the membrane-tethered ligand may be anchored to the cell membrane through a transmembrane polypeptide or a glycosylphosphatidylinositol (GPI) anchor. In some embodiments, the fragment of the native membrane-tethered ligand is an ectodomain fragment.

[0182] In some embodiments, the cell receptor is selected from: CD 166 antigen (CD 166; encoded for by ALCAM gene, UniProt: Q13740), OX-2 membrane glycoprotein (encoded for by CD200 gene, UniProt: P41217), T-lymphocyte activation antigen CD86 (encoded for by CD86 gene, UniProt: P42081), epithelial cell adhesion molecule (EpCAM, encoded for by EPCAM gene, UniProt: Pl 6422), receptor activator nuclear factor-KB (RANK, encoded for by TNFRSF11A gene, GeneBank: AAB86809.1), C-C motif chemokine (CCL19, encoded for by CCL19 gene, UniProt: Q99731), C-C motif chemokine 21 (CCL21, encoded for by CCL21 gene, UniProt: P84444), lymphotoxin beta receptor (LTpR, encoded for by LTBR gene, GeneBank: AKL90505.1), MHC class II (MHCII, encoded for by MHCII gene, UniProt: P01903), cluster of differentiation 40 (CD40, encoded for by CD40 gene, UniProt: P29965), cluster of differentiation 80 (CD80, encoded for by CD80 gene, UniProt: P33681), cluster of differentiation 86 (CD86, encoded for by CD86 gene, UniProt: P42081), lymphocyte antigen 6D (encoded for by LY6D gene, UniProt: Q14210), polymeric immunoglobulin receptor (plgR, encoded for by PIGR gene, UniProt: P01833), LI cell adhesion molecule (LI CAM, encoded for by LI CAM gene, UniProt: P32004), leukemia inhibitory factor receptor (LIFR, encoded for by LIFR gene, UniProt: P42702), integrin alpha-6 (encoded for by ITGA6 gene, UniProt: P23229), integrin beta (encoded for by ITGB4 gene, UniProt: P16144), podoplanin (encoded for by PDPN gene, UniProt: Q86YL7), chemokine (C-C motif) receptor 7 (CCR7, encoded for by CCR7 gene, UniProt: P32248), signal transducer (CD24, encoded for by CD24 gene, UniProt: P25063), CD63 molecule (CD63, encoded for by CD63 gene, UniProt: P08962), CD70 molecule (CD70, encoded for by CD70 gene, UniProt: P32970), H-2 class II histocompatibility antigen gamma chain (CD74, encoded for by CD74 gene, UniProt: P04233), T-lymphocyte activation antigen CD80 (CD80, encoded for by CD80 gene, UniProt: P33681), tetraspanin (CD81, encoded for by CD81 gene, UniProt: P60033), CD9 antigen (CD9, encoded for by CD9 gene, UniProt: P21926), cadherin-1 (encoded for by CDH1 gene, UniProt: P12830), cadherin-2 (encoded for by CDH2 gene, UniProt: Pl 9022), C-type lectin domain family 7 member A (CLEC7A; dectin-1, encoded for by CLEC7A gene, UniProt: Q9BXN2), receptor protein-tyrosine kinase

[0183] -21-

[0184] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0185] (HER3, encoded for by ERBB3 gene, UniProt: P21860), CD23 antigen (FCER2; encoded for by FCER2 gene, UniProt: P06734), interleukin 20 receptor subunit beta (IL-20RB, encoded for by IL20RB gene, UniProt: Q6UXL0), lymphocyte antigen 6D (encoded for by LY6D gene, UniProt: QI 4210), lymphocyte antigen 75 (encoded for by LY75 gene, UniProt: 060449), LY6 / PLAUR domain containing 3 (encoded for by LYPD3 gene, UniProt: 095274), macrophage receptor MARCO (“MARCO”; encoded for by MARCO gene, UniProt: Q9UEW3), oncostatin-M-specific receptor subunit beta (encoded for by OSMR gene, UniProt: Q99650), syndecan 1 (SCD1 ; encoded for by SDC1 gene, UniProt: P18827), syndecan-4 (encoded for by SDC4 gene, UniProt: P31431), kunitz-type protease inhibitor 2 (HAI-2, encoded for by SPINT2 gene, UniProt: 043291), tumor-associated calcium signal transducer 2 (Trop2, encoded for by TACSTD2 gene, UniProt: P09758), extracellular calcium-sensing receptor (CaSR, encoded for by CASR gene, UniProt: P41180), acetylcholine receptor subunit alpha (nAChRalphal, encoded for by CHRNA1 gene, UniProt: P02708), acetylcholine receptor subunit delta (encoded for by CHRND gene, UniProt: Q07001), claudin-1 (encoded for by CLDN1 gene, UniProt: 095832), claudin-4 (encoded for by CLDN4 gene, UniProt: 014493), claudin-6 (encoded for by CLDN6 gene, UniProt: P56747), immunoglobulin superfamily member 1 (encoded for by IGSF1 gene, UniProt: Q8N6C5), large neutral amino acids transporter small subunit 2 (encoded for by SLC7A8 gene, UniProt: Q9UHI5), somatostatin receptor type 2 (encoded for by SSTR2 gene, UniProt: P30874), trimeric intracellular cation channel type A (encoded for by TMEM38A gene, UniProt: Q9H6F2), sialic acid-binding Ig-like lectin 10 (SIGLEC10, encoded for by SIGLEC10 gene, UniProt: Q96LC7), growth arrest-specific gene 6 (GAS6; encoded for by gene GAS6, UniProt: Q14393), T-cell membrane protein 4 (TIM4; encoded for by gene TIMD4, UniProt: Q96H15), or any receptor on the surface of the thymic epithelial cell, and any combination thereof. The accession numbers provided for here, such as the UniProt numbers in this paragraph and throughout the present application, are incorporated by reference in its entirety, including the amino acid sequence provided therein.

[0186] In some embodiments, the cell receptor is selected from cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LT0R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin- 4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids

[0187] -22-

[0188] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T- cell membrane protein 4 (TIM4), and any combination thereof.

[0189] In some embodiments, the cell receptor is selected from CaSR, nAChRalphal, acetylcholine receptor subunit delta, claudin-1, claudin-4, claudin-6, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, somatostatin receptor type 2, TRIC-A, and any combination thereof.

[0190] In some embodiments, the cell targeting domain binds to cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LTpR, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin- 4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T- cell membrane protein 4 (TIM4), or any combination thereof.

[0191] In some embodiments, the cell targeting domain binds to CD 166 antigen. In some embodiments, the cell targeting domain binds to OX-2 membrane glycoprotein. In some embodiments, the cell targeting domain binds to T-lymphocyte activation antigen CD86. In some embodiments, the cell targeting domain binds to EpCAM. In some embodiments, the cell targeting domain binds to RANK. In some embodiments, the cell targeting domain binds to CCL19. In some embodiments, the cell targeting domain binds to CCL21. In some embodiments, the cell targeting domain binds to LT R. In some embodiments, the cell targeting domain binds to MHCII. In some embodiments, the cell targeting domain binds to CD40. In some embodiments, the cell targeting domain binds to CD80. In some embodiments, the cell targeting domain binds to CD86. In some embodiments, the cell targeting domain binds to lymphocyte antigen 6D. In some embodiments, the cell targeting

[0192] -23-

[0193] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT domain binds to plgR. In some embodiments, the cell targeting domain binds to LI CAM. In some embodiments, the cell targeting domain binds to LIFR. In some embodiments, the cell targeting domain binds to integrin alpha-6. In some embodiments, the cell targeting domain binds to integrin beta-4. In some embodiments, the cell targeting domain binds to podoplanin. In some embodiments, the cell targeting domain binds to CCR7. In some embodiments, the cell targeting domain binds to CD24. In some embodiments, the cell targeting domain binds to CD63 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to CD70. In some embodiments, the cell targeting domain binds to CD74. In some embodiments, the cell targeting domain binds to CD80. In some embodiments, the cell targeting domain binds to CD81 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to CD9 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to cadherin- 1. In some embodiments, the cell targeting domain binds to cadherin-2. In some embodiments, the cell targeting domain binds to dectin-1. In some embodiments, the cell targeting domain binds to EPCAM. In some embodiments, the cell targeting domain binds to HER3. In some embodiments, the cell targeting domain binds to CD23 antigen. In some embodiments, the cell targeting domain binds to IL-20RB. In some embodiments, the cell targeting domain binds to lymphocyte antigen 6D. In some embodiments, the cell targeting domain binds to DEC-205. In some embodiments, the cell targeting domain binds to LY6 / PLAUR domain containing 3. In some embodiments, the cell targeting domain binds to macrophage receptor MARCO. In some embodiments, the cell targeting domain binds to oncostatin-M-specific receptor subunit beta. In some embodiments, the cell targeting domain binds to syndecan 1. In some embodiments, the cell targeting domain binds to syndecan-4. In some embodiments, the cell targeting domain binds to HAI-2. In some embodiments, the cell targeting domain binds to Trop2. In some embodiments, the cell targeting domain binds to CaSR. In some embodiments, the cell targeting domain binds to nAChRalphal. In some embodiments, the cell targeting domain binds to acetylcholine receptor subunit delta. In some embodiments, the cell targeting domain binds to claudin- 1. In some embodiments, the cell targeting domain binds to claudin-4. In some embodiments, the cell targeting domain binds to claudin-6. In some embodiments, the cell targeting domain binds to immunoglobulin superfamily member 1. In some embodiments, the cell targeting domain binds to large neutral amino acids transporter small subunit 2. In some embodiments, the cell targeting domain binds to somatostatin receptor type 2. In some embodiments, the cell targeting domain binds to TRIC-A. In some embodiments, the cell targeting domain binds to sialic acid-binding Ig-

[0194] -24-

[0195] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT like lectin 10 (SIGLEC10). In some embodiments, the cell targeting domain binds to milk fat globule EGF and factor V / VIII domain containing (MFGE8). In some embodiments, the cell targeting domain binds to growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4).

[0196] In some embodiments, the cell targeting domain binds to, or specifically binds to, TROP2, CDH1, EpCAM, MARCO, or CD74.

[0197] In some embodiments, the cell targeting domain binds to cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LTpR, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin- 4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T- cell membrane protein 4 (TIM4), or any combination thereof, on the surface of a cell. In some embodiments, the cell is a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0198] In some embodiments, the cell targeting domain binds to a receptor on the surface of a thymic cell. In some embodiments, the cell targeting domain binds to a receptor on the surface of a thymic epithelial cell. In some embodiments, the cell targeting domain binds to CD 166 antigen on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to OX-2 membrane glycoprotein on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to OX-2 membrane glycoprotein on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to T-lymphocyte activation antigen CD86 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to EpCAM on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to RANK on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CCL19 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CCL21 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to LTPR on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to MHCII on the surface -25-

[0199] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT of the thymic cell. In some embodiments, the cell targeting domain binds to CD40 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD80 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD86 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to lymphocyte antigen 6D on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to plgR on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to LI CAM on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to LIFR on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to integrin alpha-6 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to integrin beta-4 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to podoplanin on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CCR7 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD24 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD63 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to CD70 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD74 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD80 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD81 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to CD9 on the surface of the thymic-derived exosome. In some embodiments, the cell targeting domain binds to cadherin-1 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to cadherin-2 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to dectin- 1 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to EPCAM on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to HER3 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CD23 antigen on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to IL-20RB on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to lymphocyte antigen 6D on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to DEC-205 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to LY6 / PLAUR domain containing 3 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to macrophage receptor MARCO on the surface of the thymic cell. In some embodiments, the cell targeting domain

[0200] -26-

[0201] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT binds to oncostatin-M-specific receptor subunit beta on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to syndecan 1 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to syndecan-4 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to HAI-2 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to Trop2 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to CaSR on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to nAChRalphal on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to acetylcholine receptor subunit delta on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to claudin-1 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to claudin-4 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to claudin-6 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to immunoglobulin superfamily member 1 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to large neutral amino acids transporter small subunit 2 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to somatostatin receptor type 2 on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to TRIC-A on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to sialic acid-binding Ig-like lectin 10 (SIGLEC10) on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to milk fat globule EGF and factor V / VIII domain containing (MFGE8) on the surface of the thymic cell. In some embodiments, the cell targeting domain binds to growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4) on the surface of the thymic cell.

[0202] In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof, that binds to a receptor on the surface of a cell. In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof, that binds to a receptor on the surface of a thymic cell. In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof, that binds to cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LTpR, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin- -27-

[0203] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0204] 4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T- cell membrane protein 4 (TIM4).

[0205] In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof, selected from an anti-CD166 antigen antibody, or the antigen-binding fragment thereof, an anti-OX-2 membrane glycoprotein antibody, or the antigen-binding fragment thereof, and anti-T-lymphocyte activation antigen CD86 antibody, or the antigenbinding fragment thereof, an anti-EpCAM antibody, or the antigen-binding fragment thereof, an anti-RANK antibody, or the antigen-binding fragment thereof, an anti-CCL19 antibody, or the antigen-binding fragment thereof, an anti-CCL21 antibody, or the antigen-binding fragment thereof, an anti-LTpR antibody, or the antigen-binding fragment thereof, an anti- MHCII antibody, or the antigen-binding fragment thereof, an anti-CD40 antibody, or the antigen-binding fragment thereof, an anti-CD80 antibody, or the antigen-binding fragment thereof, an anti-CD86 antibody, or the antigen-binding fragment thereof, an anti-lymphocyte antigen 6D antibody, or the antigen-binding fragment thereof, an anti- plgR antibody, or the antigen-binding fragment thereof, an anti-LlCAM antibody, or the antigen-binding fragment thereof, an anti-LIFR antibody, or the antigen-binding fragment thereof, an anti-integrin alpha-6 antibody, or the antigen-binding fragment thereof, an anti-integrin beta-4 antibody, or the antigen-binding fragment thereof, an anti-podoplanin antibody, or the antigen-binding fragment thereof, an anti-CCR7 antibody, or the antigen-binding fragment thereof, an anti- CD24 antibody, or the antigen-binding fragment thereof, an anti-CaSR antibody, or the antigen-binding fragment thereof, an anti-CD63 antibody, or the antigen-binding fragment thereof, an anti-nAChRalphal antibody, or the antigen-binding fragment thereof, an anti- CD70 antibody, or the antigen-binding fragment thereof, an anti-acetylcholine receptor subunit delta antibody, or the antigen-binding fragment thereof, an anti-CD74 antibody, or the antigen-binding fragment thereof, an anti-claudin-1 antibody, or the antigen-binding fragment thereof, an anti-CD80 antibody, or the antigen-binding fragment thereof, an anticlaudin-4 antibody, or the antigen-binding fragment thereof, an anti-CD81 antibody, or the antigen-binding fragment thereof, an anti-claudin-6 antibody, or the antigen-binding fragment thereof, an anti-CD9 antibody, or the antigen-binding fragment thereof, an anti-

[0206] -28-

[0207] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT immunoglobulin superfamily member 1 antibody, or the antigen-binding fragment thereof, an anti-cadherin-1 antibody, or the antigen-binding fragment thereof, an anti-large neutral amino acids transporter small subunit 2 antibody, or the antigen-binding fragment thereof, an anti- cadherin-2 antibody, or the antigen-binding fragment thereof, an anti-somatostatin receptor type 2 antibody, or the antigen-binding fragment thereof, an anti -dectin- 1 antibody, or the antigen-binding fragment thereof, an anti-TRIC-A antibody, or the antigen-binding fragment thereof, an anti-EPCAM antibody, or the antigen-binding fragment thereof, an anti-HER3 antibody, or the antigen-binding fragment thereof, an anti-CD23 antigen antibody, or the antigen-binding fragment thereof, an anti-IL-20RB antibody, or the antigen-binding fragment thereof, an anti-lymphocyte antigen 6D antibody, or the antigen-binding fragment thereof, an anti-DEC-205 antibody, or the antigen-binding fragment thereof, an anti-LY6 / PLAUR domain containing 3 antibody, or the antigen-binding fragment thereof, an anti -macrophage receptor MARCO antibody, or the antigen-binding fragment thereof, an anti-oncostatin-M- specific receptor subunit beta antibody, or the antigen-binding fragment thereof, an anti- syndecan 1 antibody, or the antigen-binding fragment thereof, an anti-syndecan-4 antibody, or the antigen-binding fragment thereof, an anti-HAI-2 antibody, or the antigen-binding fragment thereof, an anti-Trop2 antibody, or the antigen-binding fragment thereof, or any combination thereof.

[0208] In some embodiments, the cell targeting domain is an antibody, or the antigen-binding fragment thereof, that binds to a thymic epithelial cell receptor. In some embodiments, the cell targeting domain is an anti-CD166 antigen antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-OX-2 membrane glycoprotein antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti -T-lymphocyte activation antigen CD86 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti- EpCAM antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-RANK antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CCL 19 / 21 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-LT R antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-MHCII antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD40 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD80 antibody, or the antigenbinding fragment thereof, an anti-CD86 antibody, or the antigen-binding fragment thereof. In -29-

[0209] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT some embodiments, the cell targeting domain is an anti-lymphocyte antigen 6D antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti- plgR antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-LlCAM antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-LIFR antibody, or the antigenbinding fragment thereof. In some embodiments, the cell targeting domain is an anti-integrin alpha-6 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-integrin beta-4 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-podoplanin antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti- CCR7 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD24 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CaSR antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD63 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-nAChRalphal antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD70 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-acetylcholine receptor subunit delta antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD74 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-claudin-1 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD80 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-claudin-4 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD81 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-claudin-6 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD9 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-immunoglobulin superfamily member 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-cadherin-1 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-large neutral amino acids transporter small subunit 2 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-cadherin-2 antibody, or the antigen-binding fragment thereof.

[0210] -30-

[0211] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0212] In some embodiments, the cell targeting domain is an anti-somatostatin receptor type 2 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-dectin- 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-TRIC-A antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-HER3 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-CD23 antigen antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-IL-20RB antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti -lymphocyte antigen 6D antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-DEC-205 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-LY6 / PLAUR domain containing 3 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-macrophage receptor MARCO antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-oncostatin-M-specific receptor subunit beta antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-syndecan 1 antibody, or the antigenbinding fragment thereof. In some embodiments, the cell targeting domain is an anti- syndecan-4 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-HAI-2 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-Trop2 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-SIGLEClO antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-MFGE8 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-GAS6 antibody, or the antigen-binding fragment thereof. In some embodiments, the cell targeting domain is an anti-TIM4 antibody, or the antigen-binding fragment thereof.

[0213] In some embodiments, the Trop2 targeting domain binds to Trop2 on a thymic cell, a splenic cell, a dendritic cell, or a B cell. In some embodiments, the Trop2 targeting domain binds to Trop2 on the surface of a thymic cell, a splenic cell, a dendritic cell, or a B cell. In some embodiments, the Trop2 targeting domain binds to Trop2 is an anti-Trop2-antibody, or an antigen-binding fragment thereof, that binds Trop2 on the surface of a thymic cell, a splenic cell, a dendritic cell, or a B cell.

[0214] -31-

[0215] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0216] In some embodiments, the anti-Trop2 antibody, or an antigen-binding fragment thereof, is Sp293 antibody clone available from Abeam (cat. no. ab31O311). In some embodiments, the anti-Trop2 antibody, or an antigen-binding fragment thereof, is an hRS7 antibody, or the antigen-binding fragment thereof. In some embodiments, the hRS7 antibody, the antigen-binding fragment thereof, or a variant thereof, has an amino acid sequence as provided in U.S. Patent No. 8,758,752, which is hereby incorporated by reference in its entirety.

[0217] In some embodiments, the hRS7 antibody comprises a heavy chain amino acid sequence of:

[0218] QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLKWMGWIN TYTGEPTYTDDFKGRFAFSLDTSVSTAYLQI SSLKADDTAVYFCARGGFGSS YWYFDVWGQGSLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSWTVP SS SLGTQTYICNVNH KP SNTKVDKRVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRT PEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTV LHQDWLNGKEYKCKVSNKALPAP IEKTI SKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK ( SEQ ID NO : 43 ) .

[0219] In some embodiments, the hRS7 antibody comprises a light chain amino acid sequence of:

[0220] D IQLTQSP SSLSASVGDRVS ITCKASQDVS IAVAWYQQKPGKAPKLLIYSAS YRYTGVPDRFSGSGSGTDFTLT ISSLQPEDFAVYYCQQHYITPLTFGAGTKV E IKRTVAAPSVF IFPP SDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKS FNRGEC ( SEQ I D NO : 44 ) .

[0221] In some embodiments, the hRS7 antibody comprises a variable heavy chain amino acid sequence of:

[0222] QVQLQQSGSELKKPGASVKVSCKASGYTFTNYGMNWVKQAPGQGLKWMGWIN TYTGEPTYTDDFKGRFAFSLDTSVSTAYLQI SSLKADDTAVYFCARGGFGSS YWYFDVWGQGSLVTVSS ( SEQ ID NO : 45 ) .

[0223] In some embodiments, the hRS7 antibody comprises a variable light chain amino acid sequence of:

[0224] D IQLTQSP SSLSASVGDRVS ITCKASQDVS IAVAWYQQKPGKAPKLLI YSAS YRYTGVPDRFSGSGSGTDFTLT ISSLQPEDFAVYYCQQHYITPLTFGAGTKV E IK ( SEQ ID NO : 4 6 ) .

[0225] In some embodiments, the hRS7 antibody comprises a heavy chain amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 43. In some embodiments, the hRS7 antibody comprises a light chain amino acid sequence having at least 70%, at least 75%, at

[0226] -32-

[0227] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 44. In some embodiments, the hRS7 antibody comprises a variable heavy chain amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 45. In some embodiments, the hRS7 antibody comprises a variable light chain amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 46.

[0228] In some embodiments, the hRS7 antibody comprises the heavy chain amino acid sequence of SEQ ID NO: 43, and the light chain amino acid sequence of SEQ ID NO: 44. In some embodiments, the hRS7 antibody comprises the variable heavy chain amino acid sequence of SEQ ID NO: 45, and the variable light chain amino acid sequence of SEQ ID NO: 46.

[0229] In some embodiments, a dimer molecule comprises a first polypeptide comprising the heavy chain amino acid sequence of SEQ ID NO: 43, and the light chain amino acid sequence of SEQ ID NO: 44; and a second polypeptide comprising the heavy chain amino acid sequence of SEQ ID NO: 43, and the light chain amino acid sequence of SEQ ID NO: 44.

[0230] In some embodiments, the anti-Trop2 antibody, or an antigen-binding fragment thereof, is datopotamab, or a variant thereof. In some embodiment, datopotamab, or a variant thereof, comprises a variable heavy (VH) having an amino acid sequence of:

[0231] QVQLVQSGAEVKKPGASVKVSCKASGYTFTTAGMQWVRQAPGQGLEWMGWINTHSGV PKYAEDFKGRVTI SADTSTSTAYLQLSSLKSEDTAVYYCARSGFGSSYWYFDVWGQG TLVTVSS (SEQ ID NO: 47).

[0232] In some embodiments, datopotamab, or a variant thereof, comprises a variable heavy (VH) having an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 47.

[0233] In some embodiment, datopotamab, or a variant thereof, comprises a variable light (VL) having an amino acid sequence of:

[0234] D IQMTQSP SSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTG VP SRFSGSGSGTDFTLT ISSLQPEDFAVYYCQQHYITPLTFGQGTKLE IK (SEQ ID NO: 48).

[0235] -33-

[0236] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0237] In some embodiments, datopotamab, or a variant thereof, comprises a variable light (VL) having an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 48.

[0238] In some embodiments, datopotamab, or a variant thereof, comprises a variable heavy (VH) having an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 47; and a variable light (VL) having an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 48.

[0239] In some embodiments, datopotamab, or a variant thereof, comprises a variable heavy (VH) having an amino acid of SEQ ID NO: 47; and a variable light (VL) having an amino acid sequence of SEQ ID NO: 48.

[0240] In some embodiments, datopotamab, or a variant thereof, comprises a VH domain and a VL domain comprising the CDRs provided for herein. Determining CDRs is routine and can be done according to the Kabat, Chothia, IMGT numbering systems, and the like. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain and a VL domain comprising an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the VH domain and the VL domain pairs as set forth in SEQ ID NO: 47 and SEQ ID NO: 48, respectively. In some embodiments, datopotamab, or a variant thereof, comprises a VH and VL comprising an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%. 95%. 96%. 97%. 98%. or 99% identical to the VH domain and the VL domain pairs as set forth in SEQ ID NO: 47 and SEQ ID NO: 48, respectively, provided that the CDRs are identical to those in Table 3. These can be collectively referred to as a variant of the VH domain and the VL domain sequences provided for herein. In some embodiments, datopotamab, or a variant thereof, comprises the CDR sequences according to the Kabat, IMGT, or Chothia numbering systems, as provided in Table 3:

[0241] -34-

[0242] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0243] In some embodiments, the amino acid residues of the CDRs shown above contain mutations. In some embodiments, the CDRs contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 substitutions or mutations. In some embodiments, the substitution is a conservative substitution. In some embodiments, datopotamab, or a variant thereof, comprises the VH domain comprising the HCDR1 having an amino acid sequence of SEQ ID NO: 49, 55, or 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, 56, or 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51, or 57. In some embodiments, datopotamab, or a variant thereof, comprises the VL domain comprising the LCDR1 having an amino acid sequence of SEQ ID NO: 52, or 58, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, or SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises the VH domain comprising the HCDR1 having an amino acid sequence of SEQ ID NO: 49, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51; and the VL domain comprising the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises the VH domain comprising the HCDR1 having an amino acid sequence of SEQ ID NO: 55, the HCDR2 having an amino

[0244] -35-

[0245] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT acid sequence of SEQ ID NO: 56, and the HCDR3 having an amino acid sequence of SEQ ID NO: 57; and the VL domain comprising the LCDR1 having an amino acid sequence of SEQ ID NO: 58, the LCDR2 having an amino acid sequence SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises the VH domain comprising the HCDR1 having an amino acid sequence of SEQ ID NO: 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51; and the VL domain comprising the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54.

[0246] In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, 55, or 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, 56, or 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51, or 57. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 55, the HCDR2 having an amino acid sequence of SEQ ID NO: 56, and the HCDR3 having an amino acid sequence of SEQ ID NO: 57. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51.

[0247] In some embodiments, datopotamab, or a variant thereof, comprises a VL domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, -36-

[0248] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0249] 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, or 58, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, or SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a VL domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a VL domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 58, the LCDR2 having an amino acid sequence SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54.

[0250] In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, 55, or 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, 56, or 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51, or 57: and a VL domain having the amino acid sequence that is at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, or 58, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, or SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51 ; and a VL domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID -37-

[0251] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0252] NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 55, the HCDR2 having an amino acid sequence of SEQ ID NO: 56, and the HCDR3 having an amino acid sequence of SEQ ID NO: 57; and a VL domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 58, the LCDR2 having an amino acid sequence SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a VH domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 47, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51; and a VL domain having the amino acid sequence that is at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 48, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54.

[0253] In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to:

[0254] QVQLVQSGAEVKKPGASVKVSCKASGYTFTTAGMQWVRQAPGQGLEWMGWINTHSGV PKYAEDFKGRVTI SADTSTSTAYLQLSSLKSEDTAVYYCARSGFGSSYWYFDVWGQG TLVTVSSASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKP SNTKVDKRVEPKSCDKTH TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISK AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 61).

[0255] In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence of SEQ ID NO: 61.

[0256] In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a

[0257] -38-

[0258] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, 55, or 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, 56, or 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51, or 57. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 55, the HCDR2 having an amino acid sequence of SEQ ID NO: 56, and the HCDR3 having an amino acid sequence of SEQ ID NO: 57. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51.

[0259] In some embodiments, datopotamab, or a variant thereof, comprises a light chain (LC) domain having the amino acid sequence that is at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to:

[0260] DIQMTQSP SSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTG VPSRFSGSGSGTDFTLTISSLQPEDFAVYYCQQHYITPLTFGQGTKLE IKRTVAAPS VFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 62). In some embodiments, datopotamab, or a variant thereof, comprises a light chain (LC) domain having the amino acid sequence of SEQ ID NO: 62.

[0261] In some embodiments, datopotamab, or a variant thereof, comprises a light chain (LC) domain having the amino acid sequence that is at least 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, or 58, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, or SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a light chain (LC) domain having the amino acid sequence that is at least

[0262] -39-

[0263] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0264] 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a light chain (LC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 58, the LCDR2 having an amino acid sequence SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54.

[0265] In some embodiments, datopotamab. or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61; and a light chain (LC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62.

[0266] In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence of SEQ ID NO: 61; and a light chain (LC) domain having the amino acid sequence of SEQ ID NO: 62.

[0267] In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, 55, or 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, 56, or 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51, or 57; and a light chain (LC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, or 58, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, or SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 49, the HCDR2 having an amino acid sequence of SEQ ID NO: 50, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51; and a light chain (LC) domain having the amino acid sequence that is at least 90%, 91 %, 92%, 93%, 94%, 95%,

[0268] -40-

[0269] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0270] 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 55, the HCDR2 having an amino acid sequence of SEQ ID NO: 56, and the HCDR3 having an amino acid sequence of SEQ ID NO: 57; and a light chain (LC) domain having the amino acid sequence that is at least 90%. 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 58, the LCDR2 having an amino acid sequence SAS, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54. In some embodiments, datopotamab, or a variant thereof, comprises a heavy chain (HC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 61, provided that datopotamab, or a variant thereof, comprises the HCDR1 having an amino acid sequence of SEQ ID NO: 59, the HCDR2 having an amino acid sequence of SEQ ID NO: 60, and the HCDR3 having an amino acid sequence of SEQ ID NO: 51; and a light chain (LC) domain having the amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 62, provided that datopotamab, or a variant thereof, comprises the LCDR1 having an amino acid sequence of SEQ ID NO: 52, the LCDR2 having an amino acid sequence of SEQ ID NO: 53, and the LCDR3 having an amino acid sequence of SEQ ID NO: 54.

[0271] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, is as provided in, or any application related to, any one of PCT Publication Nos. WO2025179213, WO2025155626, WO2025153092, WO2025149014, W02025106470, W02025010028, WO2024213091, WO2024207177, WO2024220546, W02024206480, WO2024178310, WO2024097812, W02024050515, WO2023232746, WO2023232745, WO2023218378, WO2023209591, WO2023201267, W02020249063, W02020240467, WO2019029715, or any one of U.S. Publication Nos. US20250288687, US20250288678, US20250257146, US20250152731, US20250099605, US20250064967, US20250025568, US20250019458, US20250019457, US20240390509, US20240325564, US20240082415, US20230374149, US20230355796, US20230330248, US20230242665, US20230101735,

[0272] -41-

[0273] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0274] US20230101266, US20210395385, US20190369103, each of which is hereby incorporate by reference in its entirety.

[0275] In some embodiments, the anti-E-cadherin (CDH1) antibody, or an antigen-binding fragment thereof, is DECMA-1 antibody clone available from ThermoFisher (cat. no. 14- 3249-82). In some embodiments, the anti-MARCO antibody, or an antigen-binding fragment thereof, is the anti-MARCO antibody, or the antigen-binding fragment thereof, as disclosed in U.S. Publication No. 20220153832, which is hereby incorporated by reference in its entirety. In some embodiments, the anti-DEC205 (LY75) antibody, or an antigen-binding fragment thereof, is HD83 antibody clone available from BioLegend (cat. no. 359202). In some embodiments, the anti-CD74 antibody, or an antigen-binding fragment thereof, is lnl / CD74 antibody clone available from BioLegend (cat. no. 151002). In some embodiments, the anti-EpCAM antibody, or an antigen-binding fragment thereof, is G8.8 antibody clone available from BioLegend (cat. no. 118211). In some embodiments, the anti-FcGRII (FCER2) antibody, or an antigen-binding fragment thereof, is B3B4 antibody clone available from ThermoFisher (cat. no. 14-0232-81). In some embodiments, the anti-pIgR antibody, or an antigen-binding fragment thereof, is the anti-pIgR antibody, or the antigen-binding fragment thereof, as disclosed in U.S. Publication No. 20220112276, which is hereby incorporated by reference in its entirety.

[0276] In some embodiments, the molecule comprises a cell targeting domain that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, EpCAM, RANK, CCL19, CCL21 , LT0R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, plgR, L1CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M- specific receptor subunit beta, syndecan 1, syndecan-4, HAL2, or Trop2; and a second cell targeting domain that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T- lymphocyte activation antigen CD86, EpCAM, RANK, CCL19, CCL21, LT0R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, plgR, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7. CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2,

[0277] -42-

[0278] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, or Trop2.

[0279] In some embodiments, the molecule comprises a first cell targeting domain that binds to any one of cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LT R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL- 20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M- specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4); and a second cell targeting domain that binds to any one of cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR, CD23 antigen (FCER2), macrophage receptor MARCO, CD166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21, LTPR, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC-A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T- cell membrane protein 4 (TIM4).

[0280] In some embodiments, the molecule comprises a first cell targeting domain that binds to any one of Trop2, macrophage receptor MARCO, cadherin-1 (CDH1), Trop2, CD74, EpCAM, syndecan 1 (SDC1), plgR. CD23 antigen (FCER2), CD166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, RANK, CCL19, CCL21,

[0281] -43-

[0282] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0283] LT0R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, LI CAM, LIFR, integrin alpha- 6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1 , large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, C-type lectin domain family 7 (CLEC7A), TRIC- A, HER3, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, sialic acidbinding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4).

[0284] In some embodiments, the molecule comprises a first cell targeting domain that binds to any one of CaSR, nAChRalphal, acetylcholine receptor subunit delta, claudin-1, claudin-4, claudin-6, immunoglobulin superfamily member 1 , large neutral amino acids transporter small subunit 2, somatostatin receptor type 2, or TRIC-A; and a second cell targeting domain that binds to any one of CaSR, nAChRalphal, acetylcholine receptor subunit delta, claudin-1, claudin-4, claudin-6, immunoglobulin superfamily member 1, large neutral amino acids transporter small subunit 2, somatostatin receptor type 2, or TRIC-A.

[0285] In some embodiments, the molecule comprises a ligand amino acid sequence, or a fragment thereof. As used herein, the term “ligand” refers to a receptor or cell surface protein’s natural binding partner. In some embodiments, a ligand, or a fragment thereof, can be the full amino acid sequence, the ectodomain amino acid sequence, or the extracellular amino acid sequence. In some embodiments, the extracellular amino acid sequence does not comprise the GPI anchor. In some embodiments, the ligand, or a fragment thereof, binds to a thymic cell receptor. In some embodiments, the ligand, or a fragment thereof, binds to a thymic cell surface receptor. In some embodiments, the ligand, or a fragment thereof, binds to EpCAM, RANK, CCL19, CCL21, LT R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, plgR, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, or Trop2; and a second cell targeting domain that binds to any one of EpCAM, RANK, CCL19, CCL21, LT0R, MHCII, CD40,

[0286] -44-

[0287] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0288] CD80, CD86, lymphocyte antigen 6D. plgR, L1CAM, LIFR, integrin alpha-6, integrin beta- 4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, Trop2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4).

[0289] In some embodiments, the ligand, or a fragment thereof, binds to EpCAM. In some embodiments, the ligand, or a fragment thereof, binds to RANK. In some embodiments, the ligand, or a fragment thereof, binds to CCL19. In some embodiments, the ligand, or a fragment thereof, binds to CCL21. In some embodiments, the ligand, or a fragment thereof, binds to LTBR. In some embodiments, the ligand, or a fragment thereof, binds to MHCII. In some embodiments, the ligand, or a fragment thereof, binds to CD40. In some embodiments, the ligand, or a fragment thereof, binds to CD80. In some embodiments, the ligand, or a fragment thereof, binds to CD86. In some embodiments, the ligand, or a fragment thereof, binds to lymphocyte antigen 6D. In some embodiments, the ligand, or a fragment thereof, binds to plgR. In some embodiments, the ligand, or a fragment thereof, binds to LI CAM. In some embodiments, the ligand, or a fragment thereof, binds to LIFR. In some embodiments, the ligand, or a fragment thereof, binds to integrin alpha-6. In some embodiments, the ligand, or a fragment thereof, binds to integrin beta-4. In some embodiments, the ligand, or a fragment thereof, binds to podoplanin. In some embodiments, the ligand, or a fragment thereof, binds to CCR7. In some embodiments, the ligand, or a fragment thereof, binds to CD24. In some embodiments, the ligand, or a fragment thereof, binds to CaSR. In some embodiments, the ligand, or a fragment thereof, binds to CD63. In some embodiments, the ligand, or a fragment thereof, binds to nAChRalphal. In some embodiments, the ligand, or a fragment thereof, binds to CD70. In some embodiments, the ligand, or a fragment thereof, binds to acetylcholine receptor subunit delta. In some embodiments, the ligand, or a fragment thereof, binds to CD74. In some embodiments, the ligand, or a fragment thereof, binds to claudin-1. In some embodiments, the ligand, or a fragment thereof, binds to CD80. In some embodiments, the ligand, or a fragment thereof, binds to claudin-4. In some embodiments, the ligand, or a fragment thereof, binds to CD81. In some embodiments, the ligand, or a fragment -45-

[0290] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, binds to claudin-6. In some embodiments, the ligand, or a fragment thereof, binds to CD9. In some embodiments, the ligand, or a fragment thereof, binds to immunoglobulin superfamily member 1. In some embodiments, the ligand, or a fragment thereof, binds to cadherin-1. In some embodiments, the ligand, or a fragment thereof, binds to large neutral amino acids transporter small subunit 2. In some embodiments, the ligand, or a fragment thereof, binds to cadherin-2. In some embodiments, the ligand, or a fragment thereof, binds to somatostatin receptor type 2. In some embodiments, the ligand, or a fragment thereof, binds to dectin- 1. In some embodiments, the ligand, or a fragment thereof, binds to TRIC-A. In some embodiments, the ligand, or a fragment thereof, binds to HER3. In some embodiments, the ligand, or a fragment thereof, binds to CD23 antigen. In some embodiments, the ligand, or a fragment thereof, binds to IL-20RB. In some embodiments, the ligand, or a fragment thereof, binds to lymphocyte antigen 6D. In some embodiments, the ligand, or a fragment thereof, binds to DEC-2. In some embodiments, the ligand, or a fragment thereof, binds to LY6 / PLAUR domain containing 3. In some embodiments, the ligand, or a fragment thereof, binds to macrophage receptor MARCO. In some embodiments, the ligand, or a fragment thereof, binds to oncostatin-M-specific receptor subunit beta. In some embodiments, the ligand, or a fragment thereof, binds to syndecan 1 . In some embodiments, the ligand, or a fragment thereof, binds to syndecan-4. In some embodiments, the ligand, or a fragment thereof, binds to HAI-2. In some embodiments, the ligand, or a fragment thereof, binds to Trop2. In some embodiments, the ligand, or a fragment thereof, binds to sialic acid-binding Ig-like lectin 10 (SIGLEC10). In some embodiments, the ligand, or a fragment thereof, binds to milk fat globule EGF and factor V / VIII domain containing (MFGE8). In some embodiments, the ligand, or a fragment thereof, binds to growth arrest-specific gene 6 (GAS6). In some embodiments, the ligand, or a fragment thereof, binds to T-cell membrane protein 4 (TIM4).

[0291] In some embodiments, the polypeptide comprises a first ligand amino acid sequence, or a fragment thereof, that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, EpCAM, RANK, CCL19, CCL21, LTpR, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, plgR, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor -46-

[0292] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0293] MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, or Trop2; and a second ligand amino acid sequence, or a fragment thereof, that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, EpCAM, RANK, CCL19, CCL21, LT R, MHCII, CD40, CD80, CD86, lymphocyte antigen 6D, plgR, LI CAM, LIFR, integrin alpha-6, integrin beta-4, podoplanin, CCR7, CD24, CaSR, CD63, nAChRalphal, CD70, acetylcholine receptor subunit delta, CD74, claudin-1, CD80, claudin-4, CD81, claudin-6, CD9, immunoglobulin superfamily member 1, cadherin-1, large neutral amino acids transporter small subunit 2, cadherin-2, somatostatin receptor type 2, dectin-1, TRIC-A, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, Trop2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4).

[0294] In some embodiments, the polypeptide comprises a first ligand amino acid sequence, or a fragment thereof, that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, EpCAM, CD24, CD63, CD70, CD74, CD80, CD81, CD9, cadherin-1, cadherin-2, dectin-1, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC- 205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, or Trop2; and a second ligand amino acid sequence, or a fragment thereof, that binds to any one of CD 166 antigen, OX-2 membrane glycoprotein, T-lymphocyte activation antigen CD86, EpCAM, CD24, CD63, CD70, CD74, CD80, CD81, CD9, cadherin-1, cadherin-2, dectin-1, HER3, CD23 antigen, IL-20RB, lymphocyte antigen 6D, DEC-205, LY6 / PLAUR domain containing 3, macrophage receptor MARCO, oncostatin-M-specific receptor subunit beta, syndecan 1, syndecan-4, HAI-2, Trop2, sialic acid-binding Ig-like lectin 10 (SIGLEC10), milk fat globule EGF and factor V / VIII domain containing (MFGE8), growth arrest-specific gene 6 (GAS6), or T-cell membrane protein 4 (TIM4).

[0295] In some embodiments, the ligand, or a fragment thereof, is selected from milk fat globule EGF and factor V / VIII domain containing (MFGE8), T-cell membrane protein 4 (TIM4), growth arrest-specific gene 6 (GAS6), CD6, cell surface glycoprotein CD200 receptor 1, P-selectin, sialic acid-binding Ig-like lectin 10 (SIGLEC10), metalloproteinase inhibitor 1, lysosome-associated membrane glycoprotein 1, lysosome-associated membrane glycoprotein 2, integrin beta-1, CD27 antigen, macrophage migration inhibitory factor, CD44 antigen, cytotoxic T-lymphocyte protein 4, programmed cell death 1 ligand 1, T-cell-specific -47-

[0296] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT surface glycoprotein CD28, T-lymphocyte activation antigen CD86, complement receptor type 2, prostaglandin F2 receptor negative regulator, immunoglobulin superfamily member 8, integrin beta-1, B-lymphocyte antigen CD19, CD44 antigen, T-lymphocyte activation antigen CD80, T-cell-specific surface glycoprotein CD28, cytotoxic T-lymphocyte protein 4, membrane cofactor protein, proheparin-binding EGF-like growth factor, immunoglobulin superfamily member 8, prostaglandin F2 receptor negative regulator, integrin alpha-3, integrin alpha-6, integrin beta-1, epidermal growth factor receptor, integrin alpha-E, killer cell lectin-like receptor subfamily G member 1 , hepatocyte growth factor receptor, cadherin- 2, fibroblast growth factor receptor 1, low-density lipoprotein receptor-related protein 5, integrin beta-4, epithelial cell adhesion molecule, cadherin-1, pro-neuregulin-1, pro- neuregulin-2, complement receptor type 2, integrin alpha-X, integrin beta-2, neurogenic locus notch homolog protein 2, interleukin- 19, interleukin-20, interleukin-24, receptor-type tyrosine -protein phosphatase C, anterior gradient protein 2 homolog, secretoglobin family 3A member 2, cardiotrophin-1, leukemia inhibitory factor, oncostatin-M, kappa-casein, fibroblast growth factor 2, extracellular glycoprotein lacritin, fibroblast growth factor 2, fibroblast growth factor 2, hepatocyte growth factor, hepatocyte growth factor activator, trypsin-3, prostasin, suppressor of tumorigenicity 14 protein, and transmembrane protease serine 13.

[0297] In some embodiments, the ligand, or a fragment thereof, is CD6. In some embodiments, the ligand, or a fragment thereof, is cell surface glycoprotein CD200 receptor 1. In some embodiments, the ligand, or a fragment thereof, is P-selectin. In some embodiments, the ligand, or a fragment thereof, is sialic acid-binding Ig-like lectin 10. In some embodiments, the ligand, or a fragment thereof, is metalloproteinase inhibitor 1. In some embodiments, the ligand, or a fragment thereof, is lysosome-associated membrane glycoprotein 1. In some embodiments, the ligand, or a fragment thereof, is lysosome- associated membrane glycoprotein 2. In some embodiments, the ligand, or a fragment thereof, is integrin beta-1. In some embodiments, the ligand, or a fragment thereof, is CD27 antigen. In some embodiments, the ligand, or a fragment thereof, is macrophage migration inhibitory factor. In some embodiments, the ligand, or a fragment thereof, is CD44 antigen. In some embodiments, the ligand, or a fragment thereof, is cytotoxic T-lymphocyte protein 4. In some embodiments, the ligand, or a fragment thereof, is programmed cell death 1 ligand 1. In some embodiments, the ligand, or a fragment thereof, is T-cell-specific surface glycoprotein CD28. In some embodiments, the ligand, or a fragment thereof, is T-lymphocyte activation antigen CD86. In some embodiments, the ligand, or a fragment thereof, is complement receptor type 2. In some embodiments, the ligand, or a fragment thereof, is

[0298] -48-

[0299] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT prostaglandin F2 receptor negative regulator. In some embodiments, the ligand, or a fragment thereof, is immunoglobulin superfamily member 8. In some embodiments, the ligand, or a fragment thereof, is integrin beta-1. In some embodiments, the ligand, or a fragment thereof, is B-lymphocyte antigen CD19. In some embodiments, the ligand, or a fragment thereof, is CD44 antigen. In some embodiments, the ligand, or a fragment thereof, is T-lymphocyte activation antigen CD80. In some embodiments, the ligand, or a fragment thereof, is T-cell- specific surface glycoprotein CD28. In some embodiments, the ligand, or a fragment thereof, is cytotoxic T-lymphocyte protein 4. In some embodiments, the ligand, or a fragment thereof, is membrane cofactor protein. In some embodiments, the ligand, or a fragment thereof, is proheparin-binding EGF-like growth factor. In some embodiments, the ligand, or a fragment thereof, is immunoglobulin superfamily member 8. In some embodiments, the ligand, or a fragment thereof, is prostaglandin F2 receptor negative regulator. In some embodiments, the ligand, or a fragment thereof, is integrin alpha-3. In some embodiments, the ligand, or a fragment thereof, is integrin alpha-6. In some embodiments, the ligand, or a fragment thereof, is integrin beta-1. In some embodiments, the ligand, or a fragment thereof, is epidermal growth factor receptor. In some embodiments, the ligand, or a fragment thereof, is integrin alpha-E. In some embodiments, the ligand, or a fragment thereof, is killer cell lectin-like receptor subfamily G member 1. In some embodiments, the ligand, or a fragment thereof, is hepatocyte growth factor receptor. In some embodiments, the ligand, or a fragment thereof, is cadherin-2. In some embodiments, the ligand, or a fragment thereof, is fibroblast growth factor receptor 1 . In some embodiments, the ligand, or a fragment thereof, is low-density lipoprotein receptor-related protein 5. In some embodiments, the ligand, or a fragment thereof, is integrin beta-4. In some embodiments, the ligand, or a fragment thereof, is epithelial cell adhesion molecule. In some embodiments, the ligand, or a fragment thereof, is cadherin-1. In some embodiments, the ligand, or a fragment thereof, is pro-neuregulin- 1. In some embodiments, the ligand, or a fragment thereof, is pro-neuregulin-2. In some embodiments, the ligand, or a fragment thereof, is complement receptor type 2. In some embodiments, the ligand, or a fragment thereof, is integrin alpha-X. In some embodiments, the ligand, or a fragment thereof, is integrin beta-2. In some embodiments, the ligand, or a fragment thereof, is neurogenic locus notch homolog protein 2. In some embodiments, the ligand, or a fragment thereof, is interleukin- 19. In some embodiments, the ligand, or a fragment thereof, is interleukin-20. In some embodiments, the ligand, or a fragment thereof, is interleukin-24. In some embodiments, the ligand, or a fragment thereof, is receptor-type tyrosine-protein phosphatase C. In some embodiments, the ligand, or a fragment thereof, is

[0300] -49-

[0301] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT anterior gradient protein 2 homolog. In some embodiments, the ligand, or a fragment thereof, is secretoglobin family 3A member 2. In some embodiments, the ligand, or a fragment thereof, is cardiotrophin- 1. In some embodiments, the ligand, or a fragment thereof, is leukemia inhibitory factor. In some embodiments, the ligand, or a fragment thereof, is oncostatin-M. In some embodiments, the ligand, or a fragment thereof, is kappa-casein. In some embodiments, the ligand, or a fragment thereof, is fibroblast growth factor 2. In some embodiments, the ligand, or a fragment thereof, is extracellular glycoprotein lacritin. In some embodiments, the ligand, or a fragment thereof, is fibroblast growth factor 2. In some embodiments, the ligand, or a fragment thereof, is fibroblast growth factor 2. In some embodiments, the ligand, or a fragment thereof, is hepatocyte growth factor. In some embodiments, the ligand, or a fragment thereof, is hepatocyte growth factor activator. In some embodiments, the ligand, or a fragment thereof, is trypsin-3. In some embodiments, the ligand, or a fragment thereof, is prostasin. In some embodiments, the ligand, or a fragment thereof, is suppressor of tumorigenicity 14 protein. In some embodiments, the ligand, or a fragment thereof, is transmembrane protease serine 13.

[0302] In some embodiments, the polypeptide comprises a first ligand amino acid sequence, or a fragment thereof, selected from any one of CD6, cell surface glycoprotein CD200 receptor 1, P-selectin, sialic acid-binding Ig-like lectin 10, metalloproteinase inhibitor 1, lysosome-associated membrane glycoprotein 1, lysosome-associated membrane glycoprotein 2, integrin beta-1, CD27 antigen, macrophage migration inhibitory factor, CD44 antigen, cytotoxic T-lymphocyte protein 4, programmed cell death 1 ligand 1, T-cell-specific surface glycoprotein CD28, T-lymphocyte activation antigen CD86, complement receptor type 2, prostaglandin F2 receptor negative regulator, immunoglobulin superfamily member 8, integrin beta-1, B-lymphocyte antigen CD19, CD44 antigen, T-lymphocyte activation antigen CD80, T-cell-specific surface glycoprotein CD28, cytotoxic T-lymphocyte protein 4, membrane cofactor protein, proheparin-binding EGF-like growth factor, immunoglobulin superfamily member 8, prostaglandin F2 receptor negative regulator, integrin alpha-3, integrin alpha-6, integrin beta-1, epidermal growth factor receptor, integrin alpha-E, killer cell lectin-like receptor subfamily G member 1, hepatocyte growth factor receptor, cadherin- 2, fibroblast growth factor receptor 1, low-density lipoprotein receptor-related protein 5, integrin beta-4, epithelial cell adhesion molecule, cadherin-1, pro-neuregulin-1, pro- neuregulin-2, complement receptor type 2, integrin alpha-X, integrin beta-2, neurogenic locus notch homolog protein 2, interleukin- 19, interleukin-20, interleukin-24, receptor-type tyrosine-protein phosphatase C, anterior gradient protein 2 homolog, secretoglobin family 3A -50-

[0303] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT member 2, cardiotrophin-1, leukemia inhibitory factor, oncostatin-M, kappa-casein, fibroblast growth factor 2, extracellular glycoprotein lacritin, fibroblast growth factor 2, fibroblast growth factor 2, hepatocyte growth factor, hepatocyte growth factor activator, trypsin-3, prostasin, suppressor of tumorigenicity 14 protein, and transmembrane protease serine 13; and a second ligand amino acid sequence, or a fragment thereof, selected from any one of CD6, cell surface glycoprotein CD200 receptor 1, P-selectin, sialic acid-binding Ig-like lectin 10, metalloproteinase inhibitor 1, lysosome-associated membrane glycoprotein 1, lysosome- associated membrane glycoprotein 2, integrin beta-1, CD27 antigen, macrophage migration inhibitory factor, CD44 antigen, cytotoxic T-lymphocyte protein 4, programmed cell death 1 ligand 1, T-cell-specific surface glycoprotein CD28, T-lymphocyte activation antigen CD86. complement receptor type 2, prostaglandin F2 receptor negative regulator, immunoglobulin superfamily member 8, integrin beta-1, B-lymphocyte antigen CD 19, CD44 antigen, T- lymphocyte activation antigen CD80, T-cell-specific surface glycoprotein CD28, cytotoxic T- lymphocyte protein 4, membrane cofactor protein, proheparin-binding EGF-like growth factor, immunoglobulin superfamily member 8, prostaglandin F2 receptor negative regulator, integrin alpha-3, integrin alpha-6, integrin beta-1, epidermal growth factor receptor, integrin alpha-E, killer cell lectin-like receptor subfamily G member 1 , hepatocyte growth factor receptor, cadherin-2, fibroblast growth factor receptor 1 , low-density lipoprotein receptor- related protein 5, integrin beta-4, epithelial cell adhesion molecule, cadherin-1, pro- neuregulin-1, pro-neuregulin-2, complement receptor type 2, integrin alpha-X, integrin beta- 2, neurogenic locus notch homolog protein 2, interleukin- 19, interleukin-20, interleukin-24, receptor-type tyrosine-protein phosphatase C, anterior gradient protein 2 homolog, secretoglobin family 3 A member 2, cardiotrophin-1, leukemia inhibitory factor, oncostatin- M, kappa-casein, fibroblast growth factor 2, extracellular glycoprotein lacritin, fibroblast growth factor 2, fibroblast growth factor 2, hepatocyte growth factor, hepatocyte growth factor activator, trypsin-3, prostasin, suppressor of tumorigenicity 14 protein, and transmembrane protease serine 13.

[0304] In some embodiments, the antigen of interest is an auto-antigen, a self-antigen, a tolerance inducing antigen, or a fragment thereof. In some embodiments, the antigen is an auto-antigen, or a fragment thereof. In some embodiments, the antigen is a self-antigen, or a fragment thereof. In some embodiments, the antigen is a tolerance inducing antigen, or a fragment thereof.

[0305] In some embodiments, the cell targeting domain, such as an antibody, or an antigenbinding fragment thereof, binds to Trop2. In some embodiments, the antibody, or the

[0306] -51-

[0307] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen-binding fragment thereof is an anti-Trop2 antibody which binds to Trop2. In some embodiments, the antibody binds to amino acids of an epitope of Trop2. The Trop2 epitopes are described herein.

[0308] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope on Trop2. Trop2 is a tumor-associated calcium signal transducer 2, which has an amino acid sequence of:

[0309] MARGPGLAPPPLRLPLLLLVLAAVTGHTAAQDNCTCPTNKMTVCSPDGPGGR CQCRALGSGMAVDCSTLTSKCLLLKARMSAPKNARTLVRPSEHALVDNDGLY DPDCDPEGRFKARQCNQTSVCWCVNSVGVRRTDKGDLSLRCDELVRTHHILI DLRHRPTAGAFNHSDLDAELRRLFRERYRLHPKFVAAVHYEQPT IQIELRQN TSQKAAGDVD IGDAAYYFERD IKGESLFQGRGGLDLRVRGEPLQVERTLIYY LDE IPPKF SMKRLTAGLIAVIVWWALVAGMAVLVITNRRKSGKYKKVE IK ELGELRKEPSL (human, UniProt: P09758, SEQ ID NO: 38); or

[0310] MARGLDLAPLLLLLLAMATRFCTAQSNCTCPTNKMTVCDTNGPGGVCQCRAM GSQVLVDCSTLTSKCLLLKARMSARKSGRSLVMP SEHAI LDNDGLYDPECDD KGRFKARQCNQTSVCWCVNSVGVRRTDKGDQSLRCDEWRTHHI LIELRHRP TDRAFNHSDLDSELRRLFQERYKLHP SFLSAVHYEEPTIQIELRQNASQKGL RDVD IADAAYYFERD IKGESLFMGRRGLDVQVRGEPLHVERTLIYYLDEKPP QFSMKRLTAGVIAVIAVVSVAVVAGVWLVVTKRRKSGKYKKVELKELGEMR SEP SL (mouse, UniProt: Q8BGV3, SEQ ID NO: 39).

[0311] In some embodiments, Trop2 has an intracellular domain (ICD) comprising the amino acid sequence of:

[0312] TNRRKSGKYKKVE IKELGELRKEP SL (human; SEQ ID NO: 40);

[0313] SNRRKSGKYKKVE IKELGELRKEP SL (cynomolgus; SEQ ID NO: 41); or TKRRKSGKYKKVELKELGEMRSEP SL (mouse; SEQ ID NO: 42).

[0314] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope on human Trop2 that include Trop2 extracellular domain (ECD).

[0315] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to the intracellular domain of Trop2. In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to the amino acid sequence of SEQ ID NO: 40, SEQ ID NO: 41, or SEQ ID NO: 42. In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope of SEQ ID NO: 40, SEQ ID NO: 41, or SEQ ID NO: 42.

[0316] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope on human Trop2 that include Trop2 ICD. In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope on human Trop2 that include Trop2 ICD (SEQ ID NO: 40) residues R318, K319, E320, P321 ,

[0317] -52-

[0318] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0319] S322, and L323, or any combination thereof, as compared to SEQ ID NO: 38. In some embodiments, the epitope includes residues R318, K319, E320, P321, S322, and L323 of Trop2. In some embodiments, the epitope includes residues R318, K319, E320, P321, S322, and L323 of human Trop2. In some embodiments, the epitope includes residues R318, K319, E320, P321, S322, and L323 of Trop2 ICD. In some embodiments, the epitope includes residues R318, K319, E320, P321, S322, and L323 of human Trop2 ICD.

[0320] In some embodiments, the anti-Trop2 antibody, or the antigen-binding fragment thereof, binds to an epitope on mouse Trop2 that include Trop2 ICD (SEQ ID NO: 42) residues E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317, or any combination thereof, as compared to SEQ ID NO: 39. In some embodiments, the epitope includes residues E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317of Trop2. In some embodiments, the epitope includes residues E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317 of mouse Trop2. In some embodiments, the epitope includes residues E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317 of Trop2 ICD. In some embodiments, the epitope includes residues E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317 of mouse Trop2 ICD.

[0321] In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by a gene selected from GAD1, GAD2, INS, G6PC2, SLC30A8, PTPRN, TPM3, POLR3A, POLR3B, POLR3C, POLR3D, POLR3E, POLR3F, POLR3G, POLR3H, POLR3K, TOPI, AGTR1, EDNRA, CENPA, CENPB, CENPC, TSPAN7, GRIN1, FGF23, GRIA1, THSR, CSF2, IFNG, GRIA2. COL4A3, THSD7A, CNTNAP2, LGL1, PLA2R, MUSK, LRP4, AQP4, TRIM21, TROVE2, SNRPA1, SNRBP70, SNRPD3, HARS, TARS, ARS, IFIH1, EXOSC9, EXQSC107, PTRN, SCL30A8, PPIL2, MSH1, H4, H2AFY, H2AFJ, HIST1H2BJ, HIST1H2BA, HIST1H1C, H1F0, NCL, RCC1, CBX1, PURA, SF3B3, RMB8A, PRPF19, PRPF40A, HNRNPR, HNRNPL, HNRNPUL2, SYNCRIP, SNRNP70, EFTUD2, USP39, DHX15, SFRS1, SFRS7, SFRS2, TRA2B, TRA2A, ELAVL1, MRPL2, RPL18, MRPS27, EEF1A2, EIF3D, SSB, LRP2, MYH9, MYH10, ACTA1, ACTN4, ACTN1, LMNB2, LMNA, LMNB1, CSPG4, SPNA2, SPNB2, CLTC, TPM4, TPM1, TUBB2B, TUBA1A, MSN, PLEC1, VIM, AGRN, EPB41, TAGLN2, GM5414, ARG9A, HSPA5, HSPA11, HSP90AB1, PRDX1, YWHAE, YWHAG, YWHAH, YWHAB, SFN, ANXA2, AIFM1, DLST, DLAT, DBT, BCKDHA, AGMAT, ATP1A1, ATP1B1, ATP1A3, CPT2, PDIA4, P4HB, PDIA6, CALR, CDH16, CANX,

[0322] -53-

[0323] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0324] ALDH1L1, GANAB, PSMA8, PSMA3, PSMA4, PSMA6, PSMA7, PSMA2, PSMA1, PSMA5, PSMB4, PSMB 1, PSMB5, PSMB6, PSMB7, PSMB2, VCP, SERPINB5, PPIB, POR, MT-CO2, ILF2, APEH, COQ9, PDZK1, ACOX3, PCCA, ANPEP, CPS1, S100A11, GGT1, TGM2, GBA, GAA, GLA, NAGA, IDUA, HEXA, SMPD1, ASAHI, GALC, GALNS, ARSB, IDS, HGSNAT, GUSB, HYAL1, SIAL1, GNPTAB, GNPTG, G6PC, SLC37A4, ATP7B, PAH, ABCA4, MYOC, F8, F9, AD AMTS 13, VWF, GPIBA, GPIBB, GP5, GP6, GP9, ITGA2B, ITGB3, PF4, HLA-A, HLA-B, HLA-C, HLA-E, HLA-L, HLA-J, HLA-K, HLA-H, HLA-G, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, and HLA-DR. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GRIN1 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GAD1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GAD2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the G6PC2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SLC30A8 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PTPRN gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3B gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3C gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3D gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3E gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3F gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3G gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3H gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the AGTR1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EDNRA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CENPC gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0325] -54-

[0326] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is encoded for by the FGF23 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GRIA1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the THSR gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CSF2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the IFNG gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GRIA2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the COL4A3 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the THSD7A gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CNTNAP2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LGL1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PLA2R gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MUSK gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LRP4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the AQP4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TRIM21 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TROVE2 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SNRPA1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SNRBP70 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SNRPD3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HARS gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TARS gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ARS gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0327] -55-

[0328] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is encoded for by the IFIH1 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CENPA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CENPB gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EXOSC9 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EXOSC107 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3 A gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POLR3K gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PTRN gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the INS gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GAD2 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SCL30A8 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TSPAN7 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PPIL2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MSH1 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the H4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the H2AFY gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the H2AFJ gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HIST1H2BJ gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HIST1H2BA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HIST1H1C gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the H1F0 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the NCL gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing

[0329] -56-

[0330] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen, or a fragment thereof, is encoded for by the TOPI gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the RCC1 gene. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CBX1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PURA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SF3B3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the RMB8A gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PRPF19 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PRPF40A gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HNRNPR gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HNRNPL gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HNRNPUL2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SYNCRIP gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SNRNP70 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EFTUD2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the USP39 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the DHX15 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SFRS1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SFRS7 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SFRS2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TRA2B gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TRA2A gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ELAVL1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing

[0331] -57-

[0332] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen, or a fragment thereof, is encoded for by the MRPL2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the RPL18 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MRPS27 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EEF1 A2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EIF3D gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SSB gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LRP2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MYH9 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MYH10 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ACTA1 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ACTN4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ACTN1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LMNB2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LMNA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the LMNB1 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CSPG4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SPNA2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SPNB2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CLTC gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TPM4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TPM1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TPM3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a

[0333] -58-

[0334] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT fragment thereof, is encoded for by the TUBB2B gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TUB Al A gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MSN gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PLEC1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the VIM gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the AGRN gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the EPB41 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TAGLN2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GM5414 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ARG9A gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HSPA5 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HSPA11 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HSP90AB1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PRDX1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the YWHAE gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the YWHAG gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the YWHAH gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the YWHAB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SFN gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ANXA2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the AIFM1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the DLST gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a

[0335] -59-

[0336] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT fragment thereof, is encoded for by the DLAT gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the DBT gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the BCKDHA gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the AGMAT gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ATP 1 Al gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ATP1B1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ATP 1 A3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CPT2 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PDIA4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the P4HB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PDIA6 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CALR gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CDH16 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CANX gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ALDH1L1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GANAB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA8 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA4 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA6 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA7 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing

[0337] -60-

[0338] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen, or a fragment thereof, is encoded for by the PSMA1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMA5 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB 1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB5 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB6 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB7 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PSMB2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the VCP gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SERPINB5 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PPIB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the POR gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MT-CO2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ILF2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the APEH gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the COQ9 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PDZK1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ACOX3 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PCCA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ANPEP gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the CPS1 gene. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the S100A11 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded

[0339] -61-

[0340] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT for by the GGT1 gene. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the TGM2 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GBA gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GAA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GLA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the NAGA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the IDUA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HEXA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SMPD1 gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ASAHI gene. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GALC gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GALNS gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ARSB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the IDS gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HGSNAT gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GUSB gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HYAL1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SIAL1 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GNPTAB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GNPTG gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the G6PC gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the SLC37A4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded

[0341] -62-

[0342] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT for by the ATP7B gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PAH gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ABCA4 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the MYOC gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the F8 gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the F9 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ADAMTS13 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the VWF gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GPIBA gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GPIBB gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GP5 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GP6 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the GP9 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ITGA2B gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the ITGB3 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the PF4 gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-A gene. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-B gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-C gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-E gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-L gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-J gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-K gene. In some embodiments, the -63-

[0343] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-H gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-G gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-DM gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-DO gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-DP gene. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-DQ gene. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is encoded for by the HLA-DR gene.

[0344] In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is selected from proinsulin fragment 57-87, proinsulin fragment 57-94, glutamate decarboxylase 1 (GAD), glutamate decarboxylase 2 (GAD65), proinsulin, isletspecific glucose-6-phosphatase catalytic subunit-related protein (IGRP), zinc transporter 8 (Znt8), receptor-type tyrosine-protein phosphatase-like N (IA2), tropomyosin alpha-3 chain (TPM3), granulocyte-macrophage colony-stimulating factor (GMCSF / CSF2), RNA polymerase III complex subunit A (RNAP3), RNA polymerase III complex subunit B (RNAP3), RNA polymerase III complex subunit C (RNAP3), RNA polymerase III complex subunit D (RNAP3), RNA polymerase III complex subunit E (RNAP3), RNA polymerase III complex subunit F (RNAP3), RNA polymerase III complex subunit G (RNAP3), RNA polymerase III complex subunit H (RNAP3), RNA polymerase III complex subunit K (RNAP3), DNA topoisomerase 1 (TOPO1), type-1 angiotensin II receptor (AT1R), endothelin-1 receptor (ETAR), major centromere protein A (CENP), major centromere protein B (CENP), major centromere protein C (CENP), tetraspanin-7 (TSPAN7), 21- hydroxylase (21OH), 17alpha-hydroxylase (17OH), Th / To, ANA, dsDNA, HMGCR, myosin, SSA / Ro, SSB / La, U1RNP, U3RNP, PM-Sci, myelin basic protein (MBP), IL17 / IL22, ASMA, actin, amylase a2, GM-CSF, cyclic citrullinated proteins (CCP), snRNP, Ro52, Ro60, La, Jo-1, SRP, IFIH1, CENP A, insulin, RNA-P, U1-70K, Sm-D3, MDA-5, PL7, PL-

[0345] 12, centromere proteins, PM / SCL, RNA polymerase 3 complex, tetraspanin-7, peptidylprolyl isomerase like 2, Mlhl, proteinase-3, immunoglobulin G, immunoglobulin M, myeloperoxidase, acetylcholine receptor (AchR), MUSK, LRP4, HSP90. HSPA5, kallikrein

[0346] 13, AD AMTS 13, IFN-y, IFN-a / co, IL6, IL12 / IL23, desmogleins (e.g., desmoglein-3, desmoglein-1), aquaporin-4, myelin oligodendrocyte glycoprotein (MOG), GRIN1, GRIA1,

[0347] -64-

[0348] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0349] GRIA2, leucine rich glioma inactivated 1 protein (LGI1), neurexin family protein contactin associated protein 2 (CNTNAP2), collagen (e.g., collagen IV-alpha 3 chain (COL4A3), COL17), BP180, phospholipase A2 receptor (PLA2R), thrombospondin type-1 domaincontaining 7A (THSD7A), thyroid hormone stimulating receptor (THSR), NMD AR, FGF23, acid beta-glycosidase, acid alpha-glycosidase, alpha-galactosidase A, alpha-N- acetylgalactosaminidase, alpha-L-iduronohydrolase, beta-hexosaminidase A, sphingomyelin phosphodiesterase 1, N-acetylsphingosine amidohydrolase 1, galactocerebrosidase, N- acetylgalactosamine-sulfate sulfatase, arylsulfatase B, iduronate 2-sulfatase, heparan-alpha- glucosaminide-N-acetyltransferase, beta-glucuronidase, hyaluronidase, sialidase 1, N- acetylglucos amine- 1 -phosphotransferase alpha / beta, N-acetylglucosamine-1- phosphotransferase gamma, glucose-6-phosphatase catalytic subunit, glucose-6-phosphate transporter, ATP7B, Phenylalanine hydroxylase, ATP-binding cassette subfamily A member 4, myocilin, coagulation factor VIII, coagulation factor IX, von Willebrand factor, glycoprotein lb alpha, glycoprotein lb beta, glycoprotein V, glycoprotein VI, glycoprotein IX, glycoprotein lib, glycoprotein Illa, platelet factor 4, AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B). AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B-ATT-T, AAVPHP.B -DGT-T, AAVPHP.B -GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B-SNP(3), AAVPHP.B- SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B-STP, AAVPHP.B- PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4, AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42-10, AAV42-11, AAV42- 12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6. AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2- 15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9,

[0350] -65-

[0351] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0352] AAV3-9 / rh.52, AAV3-1 l / rh.53, AAV4- 8 / 1T1.64. AAV4-9 / rh.54, AAV4-19 / rh.55, AAV5- 3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l l, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.10 / hu.60, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAV A3.3, AAVA3.4, AAV A3.5, AAVA3.7, AAVC1. AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.l 2, AAVH6, AAVH- 1 / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40, AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721- 8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.ll, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.l 4 / 9, AAVhu.l 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV- PAEC, AAV-LK01, AAV-LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV-LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13,

[0353] -66-

[0354] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0355] AAV-LK14, AAV-LK15, AAV-LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV- PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV- PAEC12, AAV-2-pre-miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l 1, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr-7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CBr-E3, AAV CBr- E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt-6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt-Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2. AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd- B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd-N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg-F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1 , AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Civ 1-7, AAV Civ 1-8, AAV Civ 1-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv- D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv- Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv- Ml, AAV CLv-Ml 1, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv-Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv-R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4. AAV5, AAVF1 / HSC1, AAVF11 / HSC11. AAVF12 / HSC12,

[0356] AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17,

[0357] -67-

[0358] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0359] AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof), SpCas9, SaCas9, FnCasl2a, LbCasl2a, AcCasl2a, Casl3b, APOBEC1, E. coli TadA, Moloney Murine Leukemia Virus Reverse Transcriptase (M-MLV RT), HLA-A, HLA-B, HLA-C, HLA-E, HLA-L, HLA-J, HLA-K, HLA-H, HLA-G, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, and HLA-DR.

[0360] In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is proinsulin fragment 57-87. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is proinsulin fragment 57-94. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glutamate decarboxylase 1 (GAD). In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is glutamate decarboxylase 2 (GAD65). In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is zinc transporter 8 (Znt8). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is receptor-type tyrosineprotein phosphatase-like N (IA2). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is tropomyosin alpha-3 chain (TPM3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is granulocyte-macrophage colony-stimulating factor (GMCSF / CSF2). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit A (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit B (RNAP3). In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit C (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit D (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit E (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit F (RNAP3). In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit G (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase III complex subunit H (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0361] -68-

[0362] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is RNA polymerase III complex subunit K (RNAP3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is DNA topoisomerase 1 (TOPO1). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is type-1 angiotensin II receptor (AT1R). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is endothelin-1 receptor (ETAR). In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is major centromere protein A (CENP). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is major centromere protein B (CENP). In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is major centromere protein C (CENP). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is tetraspanin-7 (TSPAN7). In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is proinsulin. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is 21 -hydroxylase (21 OH). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is 17alpha-hydroxylase (17OH). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Th / To. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is ANA. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is dsDNA. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HMGCR. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is myosin. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is SSA / Ro. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is SSB / La. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is U1RNP. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is U3RNP. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is PM-Sci. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is myelin basic protein (MBP). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IL17 / IL22. In some embodiments, the auto-antigen, self-antigen,

[0363] -69-

[0364] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT tolerance inducing antigen, or a fragment thereof, is ASMA. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is actin. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is amylase a2. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is GM-CSF. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is cyclic citrullinated proteins (CCP). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is snRNP. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Ro52. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Ro60. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is La. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Jo-1. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is SRP. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IFIH1. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is CENPA. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNAP3. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is insulin. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Znt8. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA-P. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is U1-70K. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is Sm-D3. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is MDA-5. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is PL7. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is PL-12. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is a centromere protein. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is PM / SCL. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is RNA polymerase 3 complex. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is tetraspanin-7. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a

[0365] -70-

[0366] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT fragment thereof, is peptidylprolyl isomerase like 2. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Mlhl. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is proteinase-3. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is immunoglobulin G. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is immunoglobulin M. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is myeloperoxidase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is an acetylcholine receptor (AchR). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is MUSK. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is LRP4. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HSP90. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HSPA5. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is kallikrein 13. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is AT1R. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is ETAR. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is AD AMTS 13. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IFN-y. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IFN-d / co. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IL6. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is IL12 / IL23. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is a desmoglein. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is desmoglein-3. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is desmoglein- 1. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is aquaporin-4. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is myelin oligodendrocyte glycoprotein (MOG). In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is GRIN1. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0367] -71-

[0368] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is GRIA1. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is GRIA2. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is leucine rich glioma inactivated 1 protein (LGI1). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is neurexin family protein contactin associated protein 2 (CNTNAP2). In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is a collagen. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is collagen IV-alpha 3 chain (COL4A3). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is COL17. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is BP180. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is phospholipase A2 receptor (PLA2R). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is thrombospondin type-1 domain-containing 7A (THSD7A). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is thyroid hormone stimulating receptor (THSR). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is GMCSF (CSF2). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is NMD AR. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is FGF23. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is acid beta-glycosidase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is acid alpha-glycosidase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is alpha-galactosidase A. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is alpha-N-acetylgalactosaminidase. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is alpha-L-iduronohydrolase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is beta-hexosaminidase A. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is sphingomyelin phosphodiesterase 1 . In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is N-acetylsphingosine amidohydrolase 1. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is galactocerebrosidase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0369] -72-

[0370] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is N-acetylgalactosamine-sulfate sulfatase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is arylsulfatase B. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is iduronate 2-sulfatase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is heparan-alpha-glucosaminide-N- acetyltransferase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is beta-glucuronidase, hyaluronidase. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is sialidase 1. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is N-acetylglucosamine-1 -phosphotransferase alpha / beta. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is N-acetylglucosamine-1 -phosphotransferase gamma. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glucose-6- phosphatase catalytic subunit. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glucose-6-phosphate transporter. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is ATP7B. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is phenylalanine hydroxylase. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is ATP-binding cassette subfamily A member 4. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is myocilin. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is coagulation factor VIII. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is coagulation factor IX. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is a von Willebrand factor. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein lb alpha. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein lb beta. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein V. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein VI. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein IX. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is glycoprotein lib. In some embodiments, the auto-antigen, self-antigen, tolerance

[0371] -73-

[0372] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT inducing antigen, or a fragment thereof, is glycoprotein Illa. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is platelet factor 4. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is an AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B- DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B-ATT-T, AAVPHP.B-DGT-T, AAVPHP.B-GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B-SNP(3), AAVPHP.B-SNP, AAVPHP.B-QGT, AAVPHP.B- NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B-STP, AAVPHP.B-PQP, AAVPHP.B-SQP, AAVPHP.B- QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4, AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68. AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42- 1b, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42-10, AAV42-11, AAV42-12. AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1 , AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2-15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-1 l / rh.53, AAV4- 8 / rl 1.64, AAV4-9 / rh.54, AAV4-19 / rh.55. AAV5-3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.ll, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.10 / hu.60, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAVA3.3, AAVA3.4. AAVA3.5. AAVA3.7. AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.12, AAVH6, AAVH-l / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40. AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721-8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3,

[0373] -74-

[0374] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0375] AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.l l, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl. AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14 / 9, AAVhu.t 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl. AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31 , AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV-PAEC, AAV- LK01, AAV-LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV- LK08, AAV-LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV- LK15, AAV-LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV-PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV-PAEC12, AAV-2-pre- miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8. AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr- 7.3, AAV CBr-7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV

[0376] -75-

[0377] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0378] CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CB1-E3, AAV CB1-E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt-6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt-Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd-B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd- N4, AAV CKd-N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg- F5, AAV CLg-F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13. AAV CLvl-4, AAV Clvl-7, AAV Clvl-8, AAV Clvl-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv-D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv-Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv-Ml, AAV CLv-Mll, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6. AAV CLv-M7, AAV CLv-M8, AAV CLv- M9, AAV CLv-Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv- R6, AAV CLv-R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp- 8.10, AAV CSp-8.2, AAV CSp-8.4. AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8. , AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1 / HSC1, AAVF11 / HSC11, AAVF12 / HSC12, AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is SpCas9. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is, SaCas9. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is FnCasl2a. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is LbCasl2a. In some embodiments, the auto-antigen, self- antigen, tolerance inducing antigen, or a fragment thereof, is AcCasl2a. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is Cast 3b. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment

[0379] -76-

[0380] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is APOBEC1 (wherein APOBEC1 is from any vertebrate species). In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is E. coli TadA. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is M-MLV RT. In some embodiments, the autoantigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-A. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-B. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-C. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is HLA-E. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-L. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-J. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-K. In some embodiments, the auto-antigen, selfantigen, tolerance inducing antigen, or a fragment thereof, is HLA-H. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-G. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-DM. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-DO. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-DP. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-DQ. In some embodiments, the auto-antigen, self-antigen, tolerance inducing antigen, or a fragment thereof, is HLA-DR.

[0381] In some embodiments, the antigen of interest is an antibody, or the antigen-binding fragment thereof, or a fragment thereof.

[0382] In some embodiments, the antibody, or the antigen-binding fragment thereof, or a fragment thereof is selected from an anti -proinsulin fragment 57-87 antibody, or an antigenbinding fragment thereof, an anti -proinsulin fragment 57-94 antibody, or an antigen-binding fragment thereof, an anti-glutamate decarboxylase 1 (GAD) antibody, or the antigen-binding fragment thereof, an anti-proinsulin antibody, or the antigen-binding fragment thereof, an anti- islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) antibody, or the antigen-binding fragment thereof, an anti-zinc transporter 8 (Znt8) antibody, or the antigen-binding fragment thereof, an anti-receptor-type tyrosine-protein phosphatase-like N (IA2) antibody, or the antigen-binding fragment thereof, an anti-tropomyosin alpha-3 chain (TPM3) antibody, or the antigen-binding fragment thereof, an anti-granulocyte-macrophage

[0383] -77-

[0384] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT colony -stimulating factor (GMCSF / CSF2) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit A (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit B (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit C (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit D (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit E (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit F (RNAP3) antibody, or the antigenbinding fragment thereof, an anti-RNA polymerase III complex subunit G (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit H (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-RNA polymerase III complex subunit K (RNAP3) antibody, or the antigen-binding fragment thereof, an anti-DNA topoisomerase 1 (TOPO1) antibody, or the antigen-binding fragment thereof, an anti-type- 1 angiotensin II receptor (AT1R) antibody, or the antigen-binding fragment thereof, an anti-endothelin-1 receptor (ETAR), an anti-major centromere protein A (CENP) antibody, or the antigen-binding fragment thereof, an anti-major centromere protein B (CENP) antibody, or the antigen-binding fragment thereof, an anti-major centromere protein C (CENP) antibody, or the antigen-binding fragment thereof, an anti-tetraspanin-7 (TSPAN7) antibody, or the antigen-binding fragment thereof, an anti-21 OH antibody, or the antigen-binding fragment thereof, anti-17OH antibody, or the antigen-binding fragment thereof, anti-CCP antibody, or the antigen-binding fragment thereof, anti-Th / To antibody, or the antigen-binding fragment thereof, anti-ANA antibody, or the antigen-binding fragment thereof, anti-dsDNA antibody, or the antigen-binding fragment thereof, anti-HMGCR antibody, or the antigen-binding fragment thereof, anti-myosin antibody, or the antigenbinding fragment thereof, anti-SSA / Ro antibody, or the antigen-binding fragment thereof, anti-SSB / La antibody, or the antigen-binding fragment thereof, anti-UIRNP antibody, or the antigen-binding fragment thereof, anti-CENP antibody, or the antigen-binding fragment thereof, anti-U3RNP antibody, or the antigen-binding fragment thereof, anti-PM-Sci antibody, or the antigen-binding fragment thereof, anti-MBP antibody, or the antigen-binding fragment thereof, anti-IL17 antibody, anti-IL22 antibody, or the antigen-binding fragment thereof, anti-ASMA antibody, or the antigen-binding fragment thereof, anti-actin antibody, or the antigen-binding fragment thereof, anti-amylase a2 antibody, or the antigen-binding fragment thereof, anti-GM-CSF antibody, or the antigen-binding fragment thereof, anti- snRNP antibody, or the antigen-binding fragment thereof, anti-Ro52 antibody, or the antigen- -78-

[0385] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT binding fragment thereof, anti-Ro60 antibody, or the antigen-binding fragment thereof, anti- La antibody, or the antigen-binding fragment thereof, anti-Jo- 1 antibody, or the antigenbinding fragment thereof, anti-SRP antibody, or the antigen-binding fragment thereof, anti- IFIH1 antibody, or the antigen-binding fragment thereof, anti-CENPA antibody, or the antigen-binding fragment thereof, anti-RNAP3 antibody, or the antigen-binding fragment thereof, anti -TOPO1 antibody, or the antigen-binding fragment thereof, anti -insulin antibody, or the antigen-binding fragment thereof, anti-RNA-P antibody, or the antigen-binding fragment thereof, anti-Ul-70K antibody, or the antigen-binding fragment thereof, anti-Sm-D3 antibody, or the antigen-binding fragment thereof, anti-MDA-5 antibody, or the antigenbinding fragment thereof, anti-PL7 antibody, or the antigen-binding fragment thereof, antiPL- 12 antibody, or the antigen-binding fragment thereof, anti-centromere protein antibody, or the antigen-binding fragment thereof, anti-PM / SCL antibody, or the antigen-binding fragment thereof, anti-RNA polymerase 3 complex antibody, or the antigen-binding fragment thereof, anti-desmoglein-1 antibody, or the antigen-binding fragment thereof, anti- tetraspanin-7 antibody, or the antigen-binding fragment thereof, anti-peptidylprolyl isomerase like 2 antibody, or the antigen-binding fragment thereof, anti-Mlhl antibody, or the antigenbinding fragment thereof, anti-proteinase-3 antibody, or the antigen-binding fragment thereof, anti-immunoglobulin G antibody, or the antigen-binding fragment thereof, antiimmunoglobulin M antibody, or the antigen-binding fragment thereof, anti-myeloperoxidase antibody, or the antigen-binding fragment thereof, anti-AchR antibody, or the antigenbinding fragment thereof, anti-MUSK antibody, or the antigen-binding fragment thereof, anti-LRP4 antibody, or the antigen-binding fragment thereof, anti-HSP90 antibody, or the antigen-binding fragment thereof, anti-HSPA5 antibody, or the antigen-binding fragment thereof, anti-kallikrein 13 antibody, or the antigen-binding fragment thereof, anti-ATIR antibody, or the antigen-binding fragment thereof, anti-ETAR antibody, or the antigenbinding fragment thereof, anti-ADAMTS13 antibody, or the antigen-binding fragment thereof, anti-IFN-y antibody, or the antigen-binding fragment thereof, anti-IFN-a / oj antibody, or the antigen-binding fragment thereof, anti-IL6 antibody, or the antigen-binding fragment thereof, anti-IL12 / IL23 antibody, or the antigen-binding fragment thereof, anti-desmoglein-3 antibody, or the antigen-binding fragment thereof, anti-aquaporin-4 antibody, or the antigenbinding fragment thereof, anti-MOG antibody, or the antigen-binding fragment thereof, anti- GRIN1 antibody, or the antigen-binding fragment thereof, anti-GRIAl antibody, or the antigen-binding fragment thereof, anti-GRIA2 antibody, or the antigen-binding fragment thereof, anti-LGIl antibody, or the antigen-binding fragment thereof, anti-CNTNAP2

[0386] -79-

[0387] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antibody, or the antigen-binding fragment thereof. anti-COL4A3 antibody, or the antigenbinding fragment thereof, anti-COL17 antibody, or the antigen-binding fragment thereof, anti-BP180 antibody, or the antigen-binding fragment thereof, anti-PLA2R antibody, or the antigen-binding fragment thereof, anti-THSD7A antibody, or the antigen-binding fragment thereof, anti-THSR antibody, or the antigen-binding fragment thereof, anti-GMCSF (CSF2) antibody, or the antigen-binding fragment thereof, anti-NMDAR antibody, or the antigenbinding fragment thereof, anti-FGF23 antibody, or the antigen-binding fragment thereof, antiacid beta-glycosidase antibody, or the antigen-binding fragment thereof, anti-acid alphaglycosidase antibody, or the antigen-binding fragment thereof, anti-alpha-galactosidase A antibody, or the antigen-binding fragment thereof, anti-alpha-N-acetylgalactosaminidase antibody, or the antigen-binding fragment thereof, anti-alpha-L-iduronohydrolase antibody, or the antigen-binding fragment thereof, anti-beta-hexosaminidase A antibody, or the antigenbinding fragment thereof, anti-sphingomyelin phosphodiesterase 1 antibody, or the antigenbinding fragment thereof, anti-N-acetylsphingosine amidohydrolase 1 antibody, or the antigen-binding fragment thereof, anti-galactocerebrosidase antibody, or the antigen-binding fragment thereof, anti-N-acetylgalactosamine-sulfate sulfatase antibody, or the antigenbinding fragment thereof, anti-arylsulfatase B antibody, or the antigen-binding fragment thereof, anti-iduronate 2-sulfatase antibody, or the antigen-binding fragment thereof, anti- heparan-alpha-glucosaminide-N-acetyltransferase antibody, or the antigen-binding fragment thereof, anti-beta-glucuronidase antibody, or the antigen-binding fragment thereof, antihyaluronidase antibody, or the antigen-binding fragment thereof, anti-sialidase 1 antibody, or the antigen-binding fragment thereof, anti-N-acetylglucosamine-1 -phosphotransferase alpha / beta antibody, or the antigen-binding fragment thereof, anti-N-acetylglucosamine-1- phosphotransferase gamma antibody, or the antigen-binding fragment thereof, anti-glucose-6- phosphatase catalytic subunit antibody, or the antigen-binding fragment thereof, anti-glucose- 6-phosphate transporter antibody, or the antigen-binding fragment thereof, anti-ATP7B antibody, or the antigen-binding fragment thereof, anti-phenylalanine hydroxylase antibody, or the antigen-binding fragment thereof, anti-ATP -binding cassette subfamily A member 4 antibody, or the antigen-binding fragment thereof, anti-myocilin antibody, or the antigenbinding fragment thereof, anti-coagulation factor VIII antibody, or the antigen-binding fragment thereof, anti-coagulation factor IX antibody, or the antigen-binding fragment thereof, anti-von Willebrand factor antibody, or the antigen-binding fragment thereof, antiglycoprotein lb alpha antibody, or the antigen-binding fragment thereof, anti-glycoprotein lb beta antibody, or the antigen-binding fragment thereof, anti-glycoprotein V antibody, or the -80-

[0388] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antigen-binding fragment thereof, anti-glycoprotein VI antibody, or the antigen-binding fragment thereof, anti-glycoprotein IX antibody, or the antigen-binding fragment thereof, anti-glycoprotein lib antibody, or the antigen-binding fragment thereof, anti-glycoprotein Illa antibody, or the antigen-binding fragment thereof, anti-platelet factor 4 antibody, or the antigen-binding fragment thereof, anti-AAV capsid protein antibody, or the antigen-binding fragment thereof, (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B -ATT-T, AAVPHP.B- DGT-T, AAVPHP.B-GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B-SNP(3), AAVPHP.B-SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B-STP, AAVPHP.B-PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B- TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a. AAV3b, AAV3-3. AAV4, AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3. AAV24.1, AAV27.3, AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42- 10, AAV42-11 , AAV42-12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2-15 / rh.62. AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-ll / rh.53, AAV4- 8 / rl 1.64, AAV4- 9 / rh.54, AAV4-19 / rh.55, AAV5-3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l l, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.1O / hu.6O, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAVA3.3, AAVA3.4, AAVA3.5, AAVA3.7, AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.12, AAVH6, AAVH-l / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40,

[0389] -81-

[0390] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0391] AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721-8 / rh.43. AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.ll, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14 / 9, AAVhu.t 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl .18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV-PAEC, AAV-LK01, AAV- LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV- LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV- LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV-PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV-PAEC12, AAV-2-pre-miRNA-101 , AAV-8h. AAV- 8b, AAV-h. AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese

[0392] -82-

[0393] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0394] AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr- 7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CBr-E3, AAV CBr-E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CB1-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt- 6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt- Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10. AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd-B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd- N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg- F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Clvl-7, AAV Clvl-8, AAV Clvl-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv-D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv-Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv-Ml, AAV CLv-Ml 1, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv- Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv- R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1 / HSC1, AAVF11 / HSC11, AAVF12 / HSC12, AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof), anti-SpCas9 antibody, or the antigen-binding fragment thereof, anti-SaCas9 antibody, or the antigen-binding fragment thereof, anti-FnCasl2a antibody, or the antigen-binding fragment thereof, anti-LbCasl2a antibody, or the antigen-binding fragment thereof, anti-AcCasl2a antibody, or the antigenbinding fragment thereof, anti-Casl 3b antibody, or the antigen-binding fragment thereof, anti-APOBECl antibody, or the antigen-binding fragment thereof, anti-E. coli TadA antibody, or the antigen-binding fragment thereof, anti-M-MLV RT antibody, or the antigenbinding fragment thereof, anti-HLA-A antibody, or the antigen-binding fragment thereof,

[0395] -83-

[0396] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT anti-HLA-B antibody, or the antigen-binding fragment thereof, anti-HLA-C antibody, or the antigen-binding fragment thereof, anti-HLA-E antibody, or the antigen-binding fragment thereof, anti-HLA-L antibody, or the antigen-binding fragment thereof, anti-HLA-J antibody, or the antigen-binding fragment thereof, anti-HLA-K antibody, or the antigen-binding fragment thereof, anti-HLA-H antibody, or the antigen-binding fragment thereof, anti-HLA- G antibody, or the antigen-binding fragment thereof, anti-HLA-DM antibody, or the antigenbinding fragment thereof, anti-HLA-DO antibody, or the antigen-binding fragment thereof, anti-HLA-DP antibody, or the antigen-binding fragment thereof, anti-HLA-DQ antibody, or the antigen-binding fragment thereof, anti-HLA-DR antibody, or the antigen-binding fragment thereof.

[0397] In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -proinsulin fragment 57-87 antibody. In some embodiments, the antibody, or the antigenbinding fragment thereof, is the anti-proinsulin fragment 57-94 antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glutamate decarboxylase 1 (GAD) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -proinsulin antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) antibody. In some embodiments, the antibody, or the antigenbinding fragment thereof, is the anti-zinc transporter 8 (Znt8) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-receptor-type tyrosine-protein phosphatase-like N (IA2) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-tropomyosin alpha-3 chain (TPM3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-granulocyte-macrophage colony-stimulating factor (GMCSF / CSF2) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit A (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit B (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit C (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit D (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit E (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit F (RNAP3) antibody. In some

[0398] -84-

[0399] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit G (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit H (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase III complex subunit K (RNAP3) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-DNA topoisomerase 1 (TOPO1) antibody. In some embodiments, the antibody, or the antigenbinding fragment thereof, is the anti-type- 1 angiotensin II receptor (AT1R) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-endothelin-1 receptor (ETAR). In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-major centromere protein A (CENP) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-major centromere protein B (CENP) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-major centromere protein C (CENP) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -tetraspanin-7 (TSPAN7) antibody. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-21 OH antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-17OH antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-CCP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Th / To antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti- ANA antibody, or the antigen-binding fragment thereof, anti-dsDNA antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HMGCR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-myosin antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-SSA / Ro antibody, or the antigen-binding fragment thereof, anti-SSB / La antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-UIRNP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-CENP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-U3RNP

[0400] -85-

[0401] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-PM-Sci antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-MBP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IL17 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IL22 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ASMA antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-actin antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-amylase a2 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GM- CSF antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-snRNP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Ro52 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Ro60 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-La antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -Jo- 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-SRP antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IFIHl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-CENPA antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNAP3 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-TOPOl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-insulin antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GAD65 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment

[0402] -86-

[0403] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT thereof, is the anti-IA2 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Znt8 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA-P antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Ul-70K antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Sm-D3 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-MDA-5 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-PL7 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-PL-12 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-centromere protein antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-PM / SCL antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-RNA polymerase 3 complex antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-desmoglein-1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-tetraspanin-7 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-peptidylprolyl isomerase like 2 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Mlhl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-proteinase-3 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -immunoglobulin G antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-immunoglobulin M antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the antimyeloperoxidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-AchR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding

[0404] -87-

[0405] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT fragment thereof, is the anti-MUSK antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-LRP4 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HSP90 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HSPA5 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-kallikrein 13 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ATIR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ETAR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -AD AMTS 13 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IFN-y antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IFN-a / co antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IL6 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-IL12 / IL23 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-desmoglein-3 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-aquaporin-4 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti- MOG antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GRIN 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GRIAl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GRIA2 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-LGIl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-CNTNAP2 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-COL4A3 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding

[0406] -88-

[0407] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT fragment thereof, is the anti-COL17 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -BP 180 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-PLA2R antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-THSD7A antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-THSR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-GMCSF (CSF2) antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-NMDAR antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-FGF23 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-acid beta-glycosidase antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-acid alpha-glycosidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-alpha-galactosidase A antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-alpha-N- acetylgalactosaminidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-alpha-L- iduronohydrolase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-beta-hexosaminidase A antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-sphingomyelin phosphodiesterase 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigenbinding fragment thereof, is the anti-N-acetylsphingosine amidohydrolase 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-galactocerebrosidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-N-acetylgalactosamine-sulfate sulfatase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ary Isulfatase B antibody, or the antigen-binding fragment thereof, anti-iduronate 2- sulfatase antibody, or the antigen-binding fragment thereof. In some embodiments, the

[0408] -89-

[0409] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antibody, or the antigen-binding fragment thereof, is the anti-heparan-alpha-glucosaminide- N-acetyltransferase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-beta-glucuronidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-hyaluronidase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-sialidase 1 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-N- acetylglucosamine-1- anti-phosphotransferase alpha / beta antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-N-acetylglucosamine-l-phosphotransferase gamma antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glucose-6-phosphatase catalytic subunit antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glucose-6-phosphate transporter antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ATP7B antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Phenylalanine hydroxylase antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-ATP-binding cassette subfamily A member 4 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-myocilin antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti -coagulation factor VIII antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-coagulation factor IX antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-von Willebrand factor antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein lb alpha antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein lb beta antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein V antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the -90-

[0410] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT anti-glycoprotein VI antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein IX antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein lib antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-glycoprotein Illa antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-platelet factor 4 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B- EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B-ATT-T, AAVPHP.B-DGT-T, AAVPHP.B-GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B- SNP(3), AAVPHP.B-SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B- STP, AAVPHP.B-PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4. AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42- 10, AAV42-11, AAV42-12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2-15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-ll / rh.53, AAV4- 8 / rl 1.64, AAV4- 9 / rh.54, AAV4-19 / rh.55, AAV5-3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l l, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.1O / hu.6O, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25,

[0411] -91-

[0412] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0413] AAV A3.3, AAV A3.4, AAV A3.5, AAV A3.7, AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.12, AAVH6, AAVH-l / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40, AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721-8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.ll, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14 / 9, AAVhu.t 19, AAVrh.2, AAVrh.2R. AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV-PAEC, AAV-LK01, AAV- LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV- LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV- LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV-PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV-PAEC12, AAV-2-pre-miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61

[0414] -92-

[0415] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0416] AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr- 7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CBr-E3, AAV CBr-E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CB1-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt- 6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt- Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd-B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd- N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg- F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1. AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Clvl-7, AAV Clvl-8, AAV Clvl-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv-D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv-Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv-Ml, AAV CLv-Ml 1 , AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv- Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv- R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1 / HSC1, AAVF11 / HSC11, AAVF12 / HSC12, AAVF13 / HSC13. AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof) antibody, or the antigenbinding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-SpCas9 antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-SaCas9

[0417] -93-

[0418] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-FnCas!2a antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-LbCas!2a antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-AcCasl2a antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-Casl 3b antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-APOBECl antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-E. coli TadA antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-M-MLV RT antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-A antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-B antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-C antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-E antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-L antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-J antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-K antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-H antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-G antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-DM antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-DO antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-DP antibody, or the antigen-binding fragment thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-DQ antibody, or the antigen-binding fragment thereof. In some

[0419] -94-

[0420] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT embodiments, the antibody, or the antigen-binding fragment thereof, is the anti-HLA-DR antibody, or the antigen-binding fragment thereof.

[0421] In some embodiments, the antigen of interest is an effector peptide or an effector molecule. In some embodiments, the effector peptide or the effector molecule is a peptide or a molecule capable of eliciting an autoimmune response. In some embodiments, the effector peptide or the effector molecule is an antigen, an allergen, or a pollen. In some embodiments, the terms “allergen” and “pollen” may be used interchangeably. In some embodiments, the allergen, or pollen, elicits an allergic reaction. In some embodiments, the allergic reaction is a reaction to abalone, absinthe wormwood, acacia pollen, African whitewood, Alaska Pollock, alder, almond, American cockroach, American house dust mite, American lobster, American oyster, annual mercury grass, apple, apricot, Arizona cypress, arthropod, Asian green mussel, Asian hornet, Asian needle ant, Asian seabass, Asian tiger mosquito, asinus, Atlantic cod, Atlantic herring, Atlantic mackerel, Australian jumper ant, avocado, bacteria, Bahia grass, Baltic cod, banana, banana prawn, barley, beet, bell pepper, Benguela hake, bent grass, Bermuda grass, bigfin reef squid, birch, biting midges, black fire ant, black gram, black mold, black mulberry, black polar, black tiger shrimp, black walnut, blue hake, blue lupin, blue swimmer crab, booklouse, bovine, brazil nut, Brazilian fire ant, bread mold, bread wheat, brook trout, brown garden snail, brown shrimp, buckwheat, bumblebee, California sagebrush, canary grass, capillary wormwood, caridean shrimp, carp, carrot, cashew, cassava, castor bean, cat, cedar, celery, cherry, chicken, chickling vetch, chickpea, Chinese mitten crab, Chinese razor clam, Chinese white shrimp, Chinese date, chironji, chub mackerel, chum salmon, clam, climber, coconut palm, coffee, common amaranth, common buckwheat, common cypress, common mold, common mugwort, common olive, common ragweed, common roundworm, common sagebrush, common timothy, corn, crab, crayfish, crimson seabream, crustacean, cuttlefish, dandruff-associated fungus, danube crayfish, date palm, deep-water cape hake, dessert banana, disk abalone, dog, domestic guinea pig, dust mite, eastern oyster, eggplant, English walnut, European ash, European beech, European chestnut, European hake, European hazelnut, European hop hornbeam, European hornet, European house dust mite, European paper wasp, European pigeon tick, European rabbit, European white birch, fennel, feverfew, field mustard, fish worm, nematode, fishtail palm, flametree, royal Poinciana, flat fish, fleshy prawn, Formosan subterranean termite, frog, fungus, german cockroach, giant bull ant, giant honeybee, giant Madagascar hissing cockroach, giant mealworm beetle, giant mud crab, giant ragweed, giant river prawn, gold kiwi fruit, golden hamster, gould’s razor shell, grape, grass carp, greasyback shrimp, greater wax moth, green

[0422] -95-

[0423] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT kiwifruit, green mud crab, hardy kiwi, hardy pecan, hemp, herring worm, hinoki cypress, false cypress, holly oak, honeybee, hornbeam, hornet, horse, horse fly, horsehair crab, house cricket, house dust mite, Indian date, Indian honeybee, Indian mackerel, Indian meal moth, Italian cypress, itch mite, Japanese apricot, Japanese cedar, Japanese cypress, Japanese flying squid, Japanese hop, Japanese horse mackerel, Japanese rice, Japanese turban shell, Japanese white birch, Johnson grass, jumper ant, jumper, Kamchatka crab, Kentucky bluegrass, kidney bean, kiwi, kiwifruit, krill, kuruma shrimp, lemon, lentil, lesser banned hornet, lettuce, lilac, lobster, London plane tree, long-grained rice, lupine, lychee nut, Madagascar periwinkle, maize, mango, mantis shrimp, Mediterranean cypress, mesquite, mesquite pollen, methylotrophic yeast, midge, mite, mollusk, Mongolian oak, mosquito, moth, mould mite, mountain cedar, mouse, Mozambique tilapia, mugwort, mulberry, mung bean, mushroom, muskmelon, mustard, narrowleaf lupine, narrow-leaved blue lupine, narrow-leaved plantain, navel orange, neotropical wasp, netted muskmelon, noble scallop, north pacific hake, northern pink shrimp, oak, ocean perch, octopus, olive tree, orchard grass, oriental plane, papaya, paper wasp, para grass, para rubber tree, parasitic fish worm, parasitic nematode, parasitic roundworm, Patagonian grenadier, pea, peach, peanut, pear, pecan, pellitory of the wall, perennial ryegrass, pig, pigweed, pine, pine moth, pine processionary moth, pineapple, pistachio, pit -viper, plant hybrid, plum, pomegranate, Portuguese oyster, potato, privet, rainbow trout, rapeseed, raspberry, rat, red cedar, red fire ant, red squid, red swamp crayfish, rice, ringworm fungus, rivet wheat, rough pigweed, Russian thistle, rye, saffron crocus, sagebrush, salmon, sapodilla plum, scabies mite, schistosoma, sesame, shaggy mane, shallow-water cape hake, shan yao, sheep’s briar, short ragweed, short-tailed mamushi, shrimp, Siberian hamster, silk worm, silver hake, silver wormwood, silverfish, silvery wormwood, skin fungus, smokybrown cockroach, snake venom, snow crab, south American pilchard, southern hake, southern house mosquito, southern pacific hake, soybean, spotless smooth-hound, stone pine, storage mite, strawberry, striped hairy -footed hamster, summer cypress, sunflower, sweet orange, sweet vernal grass, sweet wormwood, swordfish, tall fescue, tapeworm, thistle, tomato, tobacco, tropical fire ant, trumpet lily, tsetse fly, turnip, veined rapa whelk, velvet grass, walleye Pollock, wasp, watermelon, weed, western conenose, western king prawn, western ragweed, wheat, white legged freshwater shrimp, white lupine, white mulberry, white mustard, white oak, white shrimp, whiteface hornet, whiteleg shrimp, wild boar, wild cabbage, winter squash, wolf herring, wolfberry, wormwood, wrinkled Neptune, yak, yeast, yellow fever mosquito, yellow jacket, yellow lupine, yellow mealworm, and yellowfin tuna.

[0424] -96-

[0425] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0426] In some embodiments, the allergen, or pollen, is selected from Table 2 of U.S. Provisional Application No. 63 / 496,535, filed April 17, 2023, which is hereby incorporated by reference in its entirety.

[0427] In some embodiments, the allergen, or pollen, has an amino acid sequence as provided in respective Accession number in the Comprehensive Protein Allergen Resource (COMPARE) Database (as accessed at the date of April 17, 2023), which is hereby incorporated by reference in its entirety.

[0428] In some embodiments, the antigen of interest comprises a payload. In some embodiments, the payload is an antigen, an allergen, or a pollen. In some embodiments, the payload comprises an antigen is selected from proinsulin fragment 57-87, proinsulin fragment 57-94, glutamate decarboxylase 1 (GAD), glutamate decarboxylase 2 (GAD65), proinsulin, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), zinc transporter 8 (Znt8), receptor-type tyrosine-protein phosphatase-like N (IA2), tropomyosin alpha-3 chain (TPM3), granulocyte -macrophage colony-stimulating factor (GMCSF / CSF2), RNA polymerase III complex subunit A (RNAP3), RNA polymerase III complex subunit B (RNAP3), RNA polymerase III complex subunit C (RNAP3), RNA polymerase III complex subunit D (RNAP3), RNA polymerase III complex subunit E (RNAP3), RNA polymerase III complex subunit F (RNAP3), RNA polymerase III complex subunit G (RNAP3), RNA polymerase III complex subunit H (RNAP3), RNA polymerase III complex subunit K (RNAP3), DNA topoisomerase 1 (TOPO1), type-1 angiotensin II receptor (AT1R), endothelin-1 receptor (ETAR), major centromere protein A (CENP), major centromere protein B (CENP), major centromere protein C (CENP), tetraspanin-7 (TSPAN7), 21- hydroxylase (21OH), 17alpha-hydroxylase (17OH), Th / To, ANA, dsDNA, HMGCR, myosin, SSA / Ro, SSB / La, U1RNP, U3RNP, PM-Sci, myelin basic protein (MBP), IL17 / IL22, ASMA, actin, amylase a2, GM-CSF, cyclic citrullinated proteins (CCP), snRNP, Ro52, Ro60, La, Jo-1, SRP, IFIH1, CENPA, insulin, RNA-P, U1-70K, Sm-D3, MDA-5, PL7, PL-

[0429] 12, centromere proteins, PM / SCL, RNA polymerase 3 complex, tetraspanin-7, peptidylprolyl isomerase like 2, Mlhl, proteinase-3, immunoglobulin G, immunoglobulin M, myeloperoxidase, acetylcholine receptor (AchR), MUSK, LRP4, HSP90. HSPA5, kallikrein

[0430] 13, ADAMTS13, IFN-y, IFN-a / o), IL6, IL12 / IL23, desmogleins (e.g., desmoglein-3, desmoglein-1), aquaporin-4, myelin oligodendrocyte glycoprotein (MOG), GRIN1, GRIA1, GRIA2, leucine rich glioma inactivated 1 protein (LGI1), neurexin family protein contactin associated protein 2 (CNTNAP2), collagen (e.g., collagen IV-alpha 3 chain (COL4A3), COL17), BP180, phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-

[0431] -97-

[0432] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT containing 7A (THSD7A), thyroid hormone stimulating receptor (THSR), NMD AR, FGF23, acid beta-glycosidase, acid alpha-glycosidase, alpha-galactosidase A, alpha-N- acetylgalactosaminidase, alpha-L-iduronohydrolase, beta-hexosaminidase A, sphingomyelin phosphodiesterase 1, N-acetylsphingosine amidohydrolase 1, galactocerebrosidase, N- acetylgalactosamine-sulfate sulfatase, arylsulfatase B, iduronate 2-sulfatase, heparan-alpha- glucosaminide-N-acetyltransferase, beta-glucuronidase, hyaluronidase, sialidase 1, N- acetylglucos amine- 1 -phosphotransferase alpha / beta, N-acetylglucosamine- 1 - phosphotransferase gamma, glucose-6-phosphatase catalytic subunit, glucose-6-phosphate transporter, ATP7B, Phenylalanine hydroxylase, ATP-binding cassette subfamily A member 4, myocilin, coagulation factor VIII, coagulation factor IX, von Willebrand factor, glycoprotein lb alpha, glycoprotein lb beta, glycoprotein V, glycoprotein VI, glycoprotein IX, glycoprotein lib, glycoprotein Illa, platelet factor 4, AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP. A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP. AAVPHP.B-ATT-T, AAVPHP.B -DGT-T, AAVPHP.B-GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B-SNP(3), AAVPHP.B- SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B-STP, AAVPHP.B- PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4, AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42-10, AAV42-11, AAV42- 12, AAV42-13, AAV42-15, AAV42-aa. AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25. AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2- 15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-1 l / rh.53, AAV4- 8 / rll.64, AAV4-9 / rh.54, AAV4-19 / rh.55, AAV5- 3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l 1, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42,

[0433] -98-

[0434] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0435] AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.10 / hu.60, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAVA3.3, AAVA3.4, AAV A3.5, AAVA3.7, AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.l 2, AAVH6, AAVH- 1 / hu.l. AAVH-5 / hu.3, AAVLG- 10 / rh.40, AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721- 8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.ll, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2. AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14 / 9, AAVhu.l 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31 , AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV- PAEC, AAV-LK01, AAV-LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV-LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV-LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV- PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV- PAEC12, AAV-2-pre-miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , -99-

[0436] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0437] AAV Shuffle 100-1 . AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr-7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CB1-E3, AAV CBr- E4, AAV CBr-E5, AAV CBr-e5, AAV CB1-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2. AAV CHt-3. AAV CHt-6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt-Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd- B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd-N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg-F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Civ 1-7, AAV Civ 1-8, AAV Civ 1-9, AAV CLv-2. AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl , AAV CLv-D2, AAV CLv-D3, AAV CLv- D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv- Kl. AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv- Ml, AAV CLv-Ml 1, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv-Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv-R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1 / HSC1, AAVF11 / HSC11, AAVF12 / HSC12, AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof), SpCas9, SaCas9, FnCasl2a, LbCasl2a, AcCasl2a, Casl3b, APOBEC1, E.

[0438] -100-

[0439] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT coli TadA, Moloney Murine Leukemia Virus Reverse Transcriptase (M-MLV RT), HLA-A, HLA-B, HLA-C, HLA-E, HLA-L, HLA-J, HLA-K, HLA-H, HLA-G, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, HLA-DR, any allergen provided herein, and any combination thereof.

[0440] In some embodiments, the antigen of interest can be referred to as an antigen binding domain. This can refer to a polypeptide, or an antibody, or the antigen-binding fragment thereof, that can bind to the antigen. For example, the polypeptide, or the antibody, or the antigen-binding fragment thereof, can be a polypeptide, or an antibody, or the antigenbinding fragment thereof, that binds to proinsulin fragment 57-87, proinsulin fragment 57-94, glutamate decarboxylase 1 (GAD), glutamate decarboxylase 2 (GAD65), proinsulin, isletspecific glucose-6-phosphatase catalytic subunit-related protein (IGRP), zinc transporter 8 (Znt8), receptor-type tyrosine-protein phosphatase-like N (IA2), tropomyosin alpha-3 chain (TPM3), granulocyte-macrophage colony-stimulating factor (GMCSF / CSF2), RNA polymerase III complex subunit A (RNAP3), RNA polymerase III complex subunit B (RNAP3), RNA polymerase III complex subunit C (RNAP3), RNA polymerase III complex subunit D (RNAP3), RNA polymerase III complex subunit E (RNAP3), RNA polymerase III complex subunit F (RNAP3), RNA polymerase III complex subunit G (RNAP3), RNA polymerase III complex subunit H (RNAP3), RNA polymerase III complex subunit K (RNAP3), DNA topoisomerase 1 (TOPO1), type-1 angiotensin II receptor (AT1R), endothelin-1 receptor (ETAR), major centromere protein A (CENP), major centromere protein B (CENP), major centromere protein C (CENP), tetraspanin-7 (TSPAN7), 21- hydroxylase (21 OH), 17alpha-hydroxylase (17OH), Th / To, ANA, dsDNA, HMGCR, myosin, SSA / Ro, SSB / La, U1RNP, U3RNP, PM-Sci, myelin basic protein (MBP), IL17 / IL22, ASMA, actin, amylase a2, GM-CSF, cyclic citrullinated proteins (CCP), snRNP, Ro52, Ro60, La, Jo-1, SRP, IFIH1, CENP A, insulin, RNA-P, U1-70K, Sm-D3, MDA-5, PL7, PL-

[0441] 12, centromere proteins, PM / SCL, RNA polymerase 3 complex, tetraspanin-7, peptidylprolyl isomerase like 2, Mlhl, proteinase-3, immunoglobulin G, immunoglobulin M, myeloperoxidase, acetylcholine receptor (AchR), MUSK, LRP4, HSP90. HSPA5, kallikrein

[0442] 13, AD AMTS 13, IFN-y, IFN-ot / (o, IL6, IL12 / IL23, desmogleins (e.g., desmoglein-3, desmoglein-1), aquaporin-4, myelin oligodendrocyte glycoprotein (MOG), GRIN1, GRIA1, GRIA2, leucine rich glioma inactivated 1 protein (LGI1), neurexin family protein contactin associated protein 2 (CNTNAP2), collagen (e.g., collagen IV-alpha 3 chain (COL4A3), COLI 7), BP 180, phospholipase A2 receptor (PLA2R), thrombospondin type-1 domaincontaining 7A (THSD7A), thyroid hormone stimulating receptor (THSR), NMD AR, FGF23, acid beta-glycosidase, acid alpha-glycosidase, alpha-galactosidase A, alpha-N-

[0443] -101-

[0444] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT acetylgalactosaminidase, alpha-L-iduronohydrolase, beta-hexosaminidase A, sphingomyelin phosphodiesterase 1, N-acetylsphingosine amidohydrolase 1, galactocerebrosidase, N- acetylgalactosamine-sulfate sulfatase, arylsulfatase B, iduronate 2-sulfatase, heparan-alpha- glucosaminide-N-acetyltransferase, beta-glucuronidase, hyaluronidase, sialidase 1, N- acetylglucosamine-1 -phosphotransferase alpha / beta, N-acetylglucosamine-1- phosphotransferase gamma, glucose-6-phosphatase catalytic subunit, glucose-6-phosphate transporter, ATP7B, Phenylalanine hydroxylase, ATP-binding cassette subfamily A member 4, myocilin, coagulation factor VIII, coagulation factor IX, von Willebrand factor, glycoprotein lb alpha, glycoprotein lb beta, glycoprotein V, glycoprotein VI, glycoprotein IX, glycoprotein lib, glycoprotein Illa, platelet factor 4, AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B-ATT-T, AAVPHP.B -DGT-T, AAVPHP.B -GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B-SNP(3), AAVPHP.B- SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B-STP, AAVPHP.B- PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4, AAV4-4, AAV6, AAV6.1 , AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11 , AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16, AAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12. AAV16.3, AAV24.1, AAV27.3. AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42-10, AAV42-11, AAV42- 12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2- 15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-1 l / rh.53, AAV4- 8 / r 11.64, AAV4-9 / rh.54, AAV4-19 / rh.55, AAV5- 3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l 1, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.1O / hu.6O, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6,

[0445] -102-

[0446] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0447] AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAVA3.3, AAVA3.4, AAV A3.5, AAVA3.7, AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.l 2, AAVH6, AAVH- 1 / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40, AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721- 8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6. AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.ll, AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R, AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.l 4 / 9, AAVhu.t 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57, AAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV- PAEC, AAV-LK01, AAV-LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV-LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV-LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV- PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV- PAEC12, AAV-2-pre-miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7. AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV

[0448] -103-

[0449] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0450] SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.21, AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr-7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CBr-E3, AAV CBr- E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1, AAV CHt-2, AAV CHt-3, AAV CHt-6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt-Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd- B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd-N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg-F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Civ 1-7, AAV Civ 1-8, AAV Civ 1-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv- D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv- Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv- Ml, AAV CLv-Ml 1, AAV CLv-M2, AAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv-Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv-R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3, AAV.VR-355, AAV3B, AAV4, AAV5, AAVF1 / HSC1, AAVF11 / HSC11, AAVF12 / HSC12, AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof), SpCas9, SaCas9, FnCasl2a, LbCasl2a, AcCasl2a, Casl3b, APOBEC1, E. coli TadA, Moloney Murine Leukemia Virus Reverse Transcriptase (M-MLV RT), HLA-A, HLA-B, HLA-C, HLA-E, HLA-L, HLA-J, HLA-K, HLA-H, HLA-G, HLA-DM, HLA-DO,

[0451] -104-

[0452] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT

[0453] HLA-DP, HLA-DQ, and HLA-DR, any allergen provided herein, and any combination thereof. In some embodiments, the antibody, or the antigen-binding fragment thereof, bound to the antigen or pollen, is further internalized by the thymic cell.

[0454] In some embodiments, the antigen of interest is an antibody, or antigen-binding fragment thereof; an antigen, or a fragment thereof; an auto-antigen, or a fragment thereof; a self-antigen, or a fragment thereof; a tolerance inducing antigen, or a fragment thereof; or a ligand, or a fragment thereof. In some embodiments, the antigen of interest is an antigen that induces an autoimmune, alloimmune, allergic, inflammatory, or anti -drug immune response. In some embodiments, the autoimmune, alloimmune, allergic, inflammatory, or anti-drug immune response is a disorder or disease selected from the group consisting of diabetes mellitus type 1, ulcerative colitis, Crohn's disease, celiac disease, systemic sclerosis, graft versus host disease (GVHD), rheumatoid arthritis, anti-AAV immune response, asthma, severe asthma, neutrophilic asthma, paucigranulocytic asthma, eosinophilic asthma, osteoarthritis, solid organ transplant, atopic dermatitis, eosinophilic esophagitis, dermatitis herpetiformis, chronic rhinosinusitis, chronic spontaneous urticaria, food allergy, antibiologic drug immune response, anti-viral immune response, anti-adenoviral immune response, anti-retroviral immune response, anti-lentiviral immune response, and-VLP immune response, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, dementia with Lewy bodies, Duchenne muscular dystrophy, cutaneous lupus myocarditis, postmyocardial infarction syndrome, postpericardiotomy syndrome, subacute bacterial endocarditis, anti -glomerular basement membrane nephritis, interstitial cystitis, lupus nephritis, membranous glomemlonephropathy, chronic kidney disease ("CKD"), autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, antisynthetase syndrome, alopecia areata, autoimmune angioedema, autoimmune progesterone dermatitis, autoimmune urticaria, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, discoid lupus erythematosus, epidermolysis bullosa acquisita, erythema nodosum, gestational pemphigoid, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IgA disease (LAD), morphea, pemphigus, pemphigus vulgaris, hidradenitis suppuritiva, pityriasis lichenoides et varioliformis acuta, Mucha-Habermann disease, psoriasis, guttate psoriasis, erythrodermic psoriasis, plaque psoriasis, pustular psoriasis, skin manifestation associated with systemic sclerosis,, vitiligo, Addison's disease, autoimmune polyendocrine syndrome (APS) type 1, autoimmune poly endocrine syndrome (APS) type 2, autoimmune polyendocrine syndrome (APS) type 3, autoimmune pancreatitis (AIP), autoimmune thyroiditis, Ord's thyroiditis, Graves’ disease, non-radiographic axial

[0455] -105-

[0456] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT spondyloarthropathy, autoimmune oophoritis, endometriosis, autoimmune orchitis, Sjogren's syndrome, dermatitis herpatiformis, autoimmune enteropathy, coeliac disease, immune related adverse events (irAEs) secondary to immune checkpoint inhibitors, microscopic colitis, autoimmune thrombocytopenia, adiposis dolorosa, adult-onset Still’s disease, ankylosing spondylitis, CREST syndrome, drug-induced lupus, enthesitis-related arthritis, eosinophilic fasciitis, Felty syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease (MCTD), palindromic rheumatism, Parry Romberg syndrome, Parsonage-Turner syndrome, psoriatic arthritis, reactive arthritis, relapsing polychondritis, retroperitoneal fibrosis, rheumatic fever, sarcoidosis, Schnitzler syndrome, systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), dermatomyositis, fibromyalgia, inclusion body myositis, myositis, myasthenia gravis, neuromyotonia, paraneoplastic cerebellar degeneration, polymyositis, acute disseminated encephalomyelitis (ADEM), acute motor axonal neuropathy, anti-N-methyl-D- aspartate (anti-NMDA) receptor encephalitis, balo concentric sclerosis, Bickerstaff s encephalitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, Hashimoto's encephalopathy, idiopathic inflammatory demyelinating diseases, Lambert- Eaton myasthenic syndrome, multiple sclerosis, oshtoran syndrome, pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), progressive inflammatory neuropathy, restless leg syndrome, stiff person syndrome, Sydenham chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, Cogan syndrome, Graves ophthalmopathy, intermediate uveitis, ligneous conjunctivitis, Mooren’s ulcer, neuromyelitis optica, opsoclonus myoclonus syndrome, optic neuritis, scleritis, Susac's syndrome, sympathetic ophthalmia, Tolosa-Hunt syndrome, autoimmune inner ear disease (AIED), Meniere's disease, Behcet's disease, eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis, granulmatosis with polyangiitis (GPA), IgA vasculitis (IgAV), Kawasaki's disease, leukocytoclastic vasculitis, lupus vasculitis, rheumatoid vasculitis, microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), polymyalgia rheumaticia, vasculitis, primary immune deficiency, Gaucher disease, Pompe disease, Fabry disease, Schindler disease, Hurler syndrome (MPS1), Tay-Sachs disease, Nieman-Pick disease, Farber lipogranulomatosis, Krabbe disease, Morquio syndrome (MPS4), mucopolysaccharidosis type VI (MPS6), Hunter syndrome (MPS2), Sanfilippo syndrome (MPS3), Sly sundrome (MPS7), hyaluronidase deficiency (MPS9), mucolipidosis type 1 (ML1), I-cell disease, mucolipidosis II (ML2), mucolipidosis III gamma (ML3C), glycogen storage disease la, glycogen storage disease lb, Wilson disease, phenylketonuria, Stargardt disease type I,

[0457] -106-

[0458] IPTS / 200142710.2 DOCKET NO. ZAG-006WO PATENT myocilin-associated glaucoma, hemophilia A, hemophilia B, hereditary or acquired thrombotic thrombocytopathic purpura (TTP), von Willebrand disease, thrombocytopenia platelet autoantigen, heparin-induced thrombocytopenia, tolerance induction for AAV gene therapy, tolerance induction for ex vivo gene editing, tolerance induction for in vivo gene editing, acquired hemophilia, antiphospholipid syndrome, aplastic anemia, autoimmune lymphoproliferative syndrome, autoimmune neutropenia, autoimmune thrombocytopenic purpura, cold agglutinin disease, essential mixed cryoglobulinemia, Evans syndrome, IgG4- related diseases, pure red cell aplasia, warm autoimmune hemolytic anemia, autoimmune gastritis, pernicious anemia, anti-sperm antibodies, autoimmune polyendocrine syndrome type 1, autoimmune polyendocrine syndrome type 2, autoimmune polyendocrine syndrome type 3, autoimmune myocarditis, cryptogenic organizing pneumonia, idiopathic pulmonary fibrosis, IgA nephropathy, post-myocardial infarction syndrome, primary biliary cholangitis, primary idiopathic dilated cardiomyopathy, anti-N-methyl-D-aspartate receptor encephalitis, autoimmune encephalitis, encephalopathy associated with autoimmune thyroid disease, episcleritis. Graves' ophthalmopathy, myelin oligodendrocyte glycoprotein disease, narcolepsy with cataplexy, cutaneous lupus erythematosus, adult-onset Still's disease, ankylosing spondylitis, juvenile arthritis, juvenile dermatomyositis, anti-neutrophil cytoplasmic antibody-associated vasculitis, polymyalgia rheumatic, purpura rheumatic, Takayasu arteritis, transplant, and xenotransplantation.

[0459] In some embodiments, the antigen of interest is proinsulin, or a fragment thereof. In some embodiments, the antigen of interest is a proinsulin fragment comprising residues 57-87 of proinsulin (SEQ ID NO: 16). In some embodiments, the proinsulin fragment 57-87 comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least

[0460] 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least

[0461] 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least

[0462] 95%, at least 96%, at least 97%, at least 98%, at least 99% sequence identity to:

[0463] EAED LQVGQVELGGGP GAGSLQP LALEGSLQ (SEQ ID NO: 63).

[0464] In some embodiments, the proinsulin fragment 57-87 comprises an amino acid sequence of SEQ ID NO: 63.

[0465] In some embodiments, the antigen of interest is a proinsulin fragment comprising residues 57-94 of proinsulin (SEQ ID NO: 16). In some embodiments, the proinsulin fragment 57-94 comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%...

Claims

DOCKET NO. ZAG-006WO PATENTWhat is claimed is:

1. A molecule comprising: a) a Trop2 targeting domain that binds to Trop2 on a thymic cell, a splenic cell, a dendritic cell, or a B cell, wherein the Trop2 targeting domain binds to: the intracellular domain of Trop2, such as to the amino acid sequence of SEQ ID NO: 40, SEQ ID NO: 41, or SEQ ID NO: 42; the extracellular domain of Trop2; or an epitope on Trop2 that comprises residues:R318, K319, E320, P321, S322, and L323, as compared to SEQ ID NO: 38; or E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315, S316, and L317, as compared to SEQ ID NO: 39; b) an autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest; and c) optionally an Fc polypeptide domain.

2. The molecule of claim 1 , wherein the thymic cell is a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, a junction thymic epithelial cell (jTEC), a thymic progenitor epithelial cell (TPEC), a proliferating TPEC, a thymic epithelial cell (TEC), a proliferating TEC, a cortical thymic epithelial cell (cTEC), a proliferating cTEC, or a proliferating mTEC.

3. The molecule of claim 2, wherein the mimetic mTEC is a basal (skin / lung) mTEC, an enterocyte / hepatocyte mTEC, a ciliated mTEC, an ionocyte mTEC, a keratinocyte mTEC, a microfold mTEC, a muscle mTEC, a neuroendocrine mTEC, a parathyroid mTEC, a secretory mTEC, a thyroid mTEC, or a tuft mTEC.

4. The molecule of any one of claims 1-3, wherein the Trop2 targeting domain is an antibody, or an antigen-binding fragment thereof.

5. The molecule of any one of claims 1-4, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest is an antibody, or antigen--240-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT binding fragment thereof; an antigen, or a fragment thereof; an auto-antigen, or a fragment thereof; a self-antigen, or a fragment thereof; a tolerance inducing antigen, or a fragment thereof; or a ligand, or a fragment thereof.

6. The molecule of any one of claims 1-5, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti -drug immune response antigen of interest is elicited by a disorder or disease selected from the group consisting of: diabetes mellitus type 1, ulcerative colitis, Crohn's disease, celiac disease, systemic sclerosis, graft versus host disease (GVHD), rheumatoid arthritis, anti-AAV immune response, asthma, severe asthma, neutrophilic asthma, paucigranulocytic asthma, eosinophilic asthma, osteoarthritis, solid organ transplant, atopic dermatitis, eosinophilic esophagitis, dermatitis herpetiformis, chronic rhinosinusitis, chronic spontaneous urticaria, food allergy, anti-biologic drug immune response, anti-viral immune response, anti- adenoviral immune response, anti-retroviral immune response, anti-lentiviral immune response, and-VLP immune response, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, dementia with Lewy bodies, Duchenne muscular dystrophy, cutaneous lupus myocarditis, postmyocardial infarction syndrome, postpericardiotomy syndrome, subacute bacterial endocarditis, anti-glomerular basement membrane nephritis, interstitial cystitis, lupus nephritis, membranous glomerulonephropathy, chronic kidney disease ("CKD"), autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, antisynthetase syndrome, alopecia areata, autoimmune angioedema, autoimmune progesterone dermatitis, autoimmune urticaria, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, discoid lupus erythematosus, epidermolysis bullosa acquisita, erythema nodosum, gestational pemphigoid, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IgA disease (LAD), morphea, pemphigus, pemphigus vulgaris, hidradenitis suppuritiva, pityriasis lichenoides et varioliformis acuta, Mucha-Habermann disease, psoriasis, guttate psoriasis, erythrodermic psoriasis, plaque psoriasis, pustular psoriasis, skin manifestation associated with systemic sclerosis,, vitiligo, Addison's disease, autoimmune polyendocrine syndrome (APS) type 1, autoimmune polyendocrine syndrome (APS) type 2, autoimmune polyendocrine syndrome (APS) type 3, autoimmune pancreatitis (AIP), autoimmune thyroiditis, Ord's thyroiditis, Graves' disease, non-radiographic axial spondyloarthropathy, autoimmune oophoritis, endometriosis, autoimmune orchitis, Sjogren's syndrome, dermatitis herpatiformis, autoimmune enteropathy, coeliac disease, immune related adverse events (irAEs) secondary to immune checkpoint inhibitors, microscopic-241-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT colitis, autoimmune thrombocytopenia, adiposis dolorosa, adult-onset Still's disease, ankylosing spondylitis, CREST syndrome, drug-induced lupus, enthesitis-related arthritis, eosinophilic fasciitis, Felty syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease (MCTD), palindromic rheumatism, Parry Romberg syndrome, Parsonage-Turner syndrome, psoriatic arthritis, reactive arthritis, relapsing polychondritis, retroperitoneal fibrosis, rheumatic fever, sarcoidosis, Schnitzler syndrome, systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), dermatomyositis, fibromyalgia, inclusion body myositis, myositis, myasthenia gravis, neuromyotonia, paraneoplastic cerebellar degeneration, polymyositis, acute disseminated encephalomyelitis (ADEM), acute motor axonal neuropathy, anti-N-methyl-D- aspartate (anti-NMDA) receptor encephalitis, balo concentric sclerosis, Bickerstaffs encephalitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, Hashimoto's encephalopathy, idiopathic inflammatory demyelinating diseases, Lambert- Eaton myasthenic syndrome, multiple sclerosis, oshtoran syndrome, pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), progressive inflammatory neuropathy, restless leg syndrome, stiff person syndrome, Sydenham chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, Cogan syndrome, Graves ophthalmopathy, intermediate uveitis, ligneous conjunctivitis, Mooren's ulcer, neuromyelitis optica, opsoclonus myoclonus syndrome, optic neuritis, scleritis, Susac's syndrome, sympathetic ophthalmia, Tolosa-Hunt syndrome, autoimmune inner ear disease (AIED), Meniere's disease, Behcet's disease, eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis, granulmatosis with polyangiitis (GPA), IgA vasculitis (IgAV), Kawasaki's disease, leukocytoclastic vasculitis, lupus vasculitis, rheumatoid vasculitis, microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), polymyalgia rheumaticia, vasculitis, primary immune deficiency, Gaucher disease, Pompe disease, Fabry disease, Schindler disease, Hurler syndrome (MPS1), Tay-Sachs disease, Nieman-Pick disease, Farber lipogranulomatosis, Krabbe disease, Morquio syndrome (MPS4), mucopolysaccharidosis type VI (MPS6), Hunter syndrome (MPS2), Sanfilippo syndrome (MPS3), Sly sundrome (MPS7), hyaluronidase deficiency (MPS9), mucolipidosis type 1 (ML1), I -cell disease, mucolipidosis II (ML2), mucolipidosis III gamma (ML3C), glycogen storage disease la, glycogen storage disease lb, Wilson disease, phenylketonuria, Stargardt disease type I, myocilin-associated glaucoma, hemophilia A, hemophilia B, hereditary or acquired thrombotic thrombocytopathic purpura (TTP), von Willebrand disease, thrombocytopenia platelet autoantigen, heparin-induced thrombocytopenia, tolerance induction for AAV gene-242-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT therapy, tolerance induction for ex vivo gene editing, tolerance induction for in vivo gene editing, acquired hemophilia, antiphospholipid syndrome, aplastic anemia, autoimmune lymphoproliferative syndrome, autoimmune neutropenia, autoimmune thrombocytopenic purpura, cold agglutinin disease, essential mixed cryoglobulinemia, Evans syndrome, IgG4- related diseases, pure red cell aplasia, warm autoimmune hemolytic anemia, autoimmune gastritis, pernicious anemia, anti-sperm antibodies, autoimmune polyendocrine syndrome type 1, autoimmune polyendocrine syndrome type 2, autoimmune polyendocrine syndrome type 3, autoimmune myocarditis, cryptogenic organizing pneumonia, idiopathic pulmonary fibrosis, IgA nephropathy, post-myocardial infarction syndrome, primary biliary cholangitis, primary idiopathic dilated cardiomyopathy, anti-N-methyl-D-aspartate receptor encephalitis, autoimmune encephalitis, encephalopathy associated with autoimmune thyroid disease, episcleritis, Graves' ophthalmopathy, myelin oligodendrocyte glycoprotein disease, narcolepsy with cataplexy, cutaneous lupus erythematosus, adult-onset Still's disease, ankylosing spondylitis, juvenile arthritis, juvenile dermatomyositis, anti-neutrophil cytoplasmic antibody-associated vasculitis, polymyalgia rheumatic, purpura rheumatic, Takayasu arteritis, transplant, and xenotransplantation.

7. The molecule of claim 1, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest is selected from the group consisting of: proinsulin fragment 57-87, proinsulin fragment 57-94, glutamate decarboxylase 1 (GAD), glutamate decarboxylase 2 (GAD65), proinsulin, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), zinc transporter 8 (Znt8), receptor-type tyrosineprotein phosphatase-like N (IA2), tropomyosin alpha-3 chain (TPM3), granulocytemacrophage colony-stimulating factor (GMCSF / CSF2), RNA polymerase III complex subunit A (RNAP3), RNA polymerase III complex subunit B (RNAP3), RNA polymerase III complex subunit C (RNAP3), RNA polymerase III complex subunit D (RNAP3), RNA polymerase III complex subunit E (RNAP3), RNA polymerase III complex subunit F (RNAP3), RNA polymerase III complex subunit G (RNAP3), RNA polymerase III complex subunit H (RNAP3), RNA polymerase III complex subunit K (RNAP3), DNA topoisomerase 1 (TOPO1), type-1 angiotensin II receptor (AT1R), endothelin-1 receptor (ETAR), major centromere protein A (CENP), major centromere protein B (CENP), major centromere protein C (CENP), tetraspanin-7 (TSPAN7), 21 -hydroxylase (21OH), 17alpha-hydroxylase (17OH), Th / To, ANA, dsDNA, HMGCR, myosin, SSA / Ro, SSB / La, U1RNP, U3RNP, PM- -243-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENTSci, myelin basic protein (MBP), IL17 / IL22, ASMA, actin, amylase a2, GM-CSF, cyclic citrullinated proteins (CCP), snRNP, Ro52, Ro60, La, Jo-1, SRP, IFIH1, CENPA, insulin, RNA-P, U1-70K, Sm-D3, MDA-5, PL7, PL-12, centromere proteins, PM / SCL, RNA polymerase 3 complex, tetraspanin-7, peptidylprolyl isomerase like 2, Mlhl, proteinase-3, immunoglobulin G, immunoglobulin M, myeloperoxidase, acetylcholine receptor (AchR), MUSK, LRP4, HSP90. HSPA5, kallikrein 13, ADAMTS13, IFN-y, IFN-a o, IL6, IL12 / IL23, desmogleins (e.g., desmoglein-3, desmoglein-1), aquaporin-4, myelin oligodendrocyte glycoprotein (MOG), GRIN1, GRIA1, GRIA2, leucine rich glioma inactivated 1 protein (LGI1), neurexin family protein contactin associated protein 2 (CNTNAP2), collagen (e.g., collagen IV-alpha 3 chain (COL4A3), COL17), BP 180, phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), thyroid hormone stimulating receptor (THSR), NMD AR, FGF23, acid beta-glycosidase, acid alpha-glycosidase, alphagalactosidase A, alpha-N-acetylgalactosaminidase, alpha-L-iduronohydrolase, betahexosaminidase A, sphingomyelin phosphodiesterase 1, N-acetylsphingosine amidohydrolase 1, galactocerebrosidase, N-acetylgalactosamine-sulfate sulfatase, arylsulfatase B, iduronate 2- sulfatase, heparan-alpha-glucosaminide-N-acetyltransferase, beta-glucuronidase, hyaluronidase, sialidase 1, N-acetylglucosamine-1 -phosphotransferase alpha / beta, N- acetylglucosamine-1 -phosphotransferase gamma, glucose-6-phosphatase catalytic subunit, glucose-6-phosphate transporter, ATP7B, Phenylalanine hydroxylase, ATP-binding cassette subfamily A member 4, myocilin, coagulation factor VIII, coagulation factor IX, von Willebrand factor, glycoprotein lb alpha, glycoprotein lb beta, glycoprotein V, glycoprotein VI, glycoprotein IX, glycoprotein lib, glycoprotein Illa, platelet factor 4, AAV capsid protein (such as AAV1, AAVrhlO, AAV-DJ, AAV-DJ8, AAV5, AAVPHP.B (PHP.B), AAVPHP.A (PHP.A), AAVG2B-26, AAVG2B-13, AAVTH1.1-32, AAVTH1.1- 35, AAVPHP.B2 (PHP.B2), AAVPHP.B3 (PHP.B3), AAVPHP.N / PHP.B-DGT, AAVPHP.B-EST, AAVPHP.B-GGT, AAVPHP.B-ATP, AAVPHP.B-ATT-T, AAVPHP.B-DGT-T, AAVPHP.B-GGT-T, AAVPHP.B-SGS, AAVPHP.B-AQP, AAVPHP.B-QQP, AAVPHP.B- SNP(3), AAVPHP.B-SNP, AAVPHP.B-QGT, AAVPHP.B-NQT, AAVPHP.B- EGS, AAVPHP.B-SGN, AAVPHP.B-EGT, AAVPHP.B-DST, AAVPHP.B-DST, AAVPHP.B- STP, AAVPHP.B-PQP, AAVPHP.B-SQP, AAVPHP.B-QLP, AAVPHP.B-TMP, AAVPHP.B-TTP, AAVPHP.eB, AAVPHP.S / G2A12, AAVG2A15 / G2A3 (G2A3), AAVG2B4 (G2B4), AAVG2B5 (G2B5), PHP.S, AAV2, AAV2G9, AAV3, AAV3a, AAV3b, AAV3-3, AAV4. AAV4-4, AAV6, AAV6.1, AAV6.2, AAV6.1.2, AAV7, AAV7.2, AAV8, AAV9.11, AAV9.13, AAV9, AAV9 K449R (or K449R AAV9), AAV9.16,-244-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENTAAV9.24, AAV9.45, AAbiodisV9.47, AAV9.61, AAV9.68, AAV9.84, AAV9.9, AAV10, AAV11, AAV12, AAV16.3, AAV24.1, AAV27.3, AAV42.12, AAV42- lb, AAV42-2, AAV42-3a, AAV42-3b, AAV42-4, AAV42-5a, AAV42-5b, AAV42-6b, AAV42-8, AAV42- 10, AAV42-11, AAV42-12, AAV42-13, AAV42-15, AAV42-aa, AAV43-1, AAV43-12, AAV43-20, AAV43-21, AAV43-23, AAV43-25, AAV43-5, AAV44.1, AAV44.2, AAV44.5, AAV223.1, AAV223.2, AAV223.4, AAV223.5, AAV223.6, AAV223.7, AAVl-7 / rh.48, AAVl-8 / rh.49, AAV2-15 / rh.62, AAV2-3 / rh.61, AAV2-4 / rh.5O, AAV2-5 / rh.51, AAV3.1 / hu.6, AAV3.1 / hu.9, AAV3-9 / rh.52, AAV3-ll / rh.53, AAV4- 8 / rl 1.64, AAV4- 9 / rh.54, AAV4-19 / rh.55, AAV5-3 / rh.57, AAV5-22 / rh.58, AAV7.3 / hu.7, AAV16.8 / hu.lO, AAV16.12 / hu.l l, AAV29.3 / bb.l, AAV29.5 / bb.2, AAV106.1 / hu.37, AAV114.3 / hu.4O, AAV127.2 / hu.41, AAV127.5 / hu.42, AAV128.3 / hu.44, AAV130.4 / hu.48, AAV145.1 / hu.53, AAV145.5 / hu.54, AAV145.6 / hu.55, AAV161.10 / hu.60, AAV161.6 / hu.61, AAV33.12 / hu.l7, AAV33.4 / hu.l5, AAV33.8 / hu.l6, AAV52 / hu.l9, AAV52.1 / hu.2O, AAV58.2 / hu.25, AAVA3.3, AAVA3.4, AAVA3.5, AAVA3.7, AAVC1, AAVC2, AAVC5, AAVF3, AAVF5, AAVH2, AAVrh.72, AAVhu.8, AAVrh.68, AAVrh.70, AAVpi.l, AAVpi.3, AAVpi.2, AAVrh.60, AAVrh.44, AAVrh.65, AAVrh.55, AAVrh.47, AAVrh.69, AAVrh.45, AAVrh.59, AAVhu.12, AAVH6, AAVH-l / hu.l, AAVH-5 / hu.3, AAVLG- 10 / rh.40, AAVLG-4 / rh.38, AAVLG-9 / hu.39, AAVN721-8 / rh.43, AAVCh.5, AAVCh.5Rl, AAVcy.2, AAVcy.3, AAVcy.4, AAVcy.5, AAVCy.5Rl, AAVCy.5R2, AAVCy.5R3, AAVCy.5R4, AAVcy.6, AAVhu.l, AAVhu.2, AAVhu.3, AAVhu.4, AAVhu.5, AAVhu.6, AAVhu.7, AAVhu.9, AAVhu.10, AAVhu.l l , AAVhu.13, AAVhu.15, AAVhu.16, AAVhu.17, AAVhu.18, AAVhu.20, AAVhu.21, AAVhu.22, AAVhu.23.2, AAVhu.24, AAVhu.25, AAVhu.27, AAVhu.28, AAVhu.29, AAVhu.29R. AAVhu.31, AAVhu.32, AAVhu.34, AAVhu.35, AAVhu.37, AAVhu.39, AAVhu.40, AAVhu.41, AAVhu.42, AAVhu.43, AAVhu.44, AAVhu.44Rl, AAVhu.44R2, AAVhu.44R3, AAVhu.45, AAVhu.46, AAVhu.47, AAVhu.48, AAVhu.48Rl, AAVhu.48R2, AAVhu.48R3, AAVhu.49, AAVhu.51, AAVhu.52, AAVhu.54, AAVhu.55, AAVhu.56, AAVhu.57, AAVhu.58, AAVhu.60, AAVhu.61, AAVhu.63, AAVhu.64, AAVhu.66, AAVhu.67, AAVhu.14 / 9, AAVhu.t 19, AAVrh.2, AAVrh.2R, AAVrh.8, AAVrh.8R, AAVrh.10, AAVrh.12, AAVrh.13, AAVrh.l3R, AAVrh.14, AAVrh.17, AAVrh.18, AAVrh.19, AAVrh.20, AAVrh.21, AAVrh.22, AAVrh.23, AAVrh.24, AAVrh.25, AAVrh.31, AAVrh.32, AAVrh.33, AAVrh.34, AAVrh.35, AAVrh.36, AAVrh.37, AAVrh.37R2, AAVrh.38, AAVrh.39, AAVrh.40, AAVrh.46, AAVrh.48, AAVrh.48.1, AAVrh.48.1.2, AAVrh.48.2, AAVrh.49, AAVrh.51, AAVrh.52, AAVrh.53, AAVrh.54, AAVrh.56, AAVrh.57,-245-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENTAAVrh.58, AAVrh.61, AAVrh.64, AAVrh.64Rl, AAVrh.64R2, AAVrh.67, AAVrh.73, AAVrh.74 (also referred to as AAVrh74), AAVrh8R, AAVrh8R A586R mutant, AAVrh8R R533A mutant, AAAV, BAAV, caprine AAV, bovine AAV, AAVhEl.l, AAVhErl.5, AAVhER1.14, AAVhErl.8, AAVhErl.16, AAVhErl.18, AAVhErl.35, AAVhErl.7, AAVhErl.36, AAVhEr2.29, AAVhEr2.4, AAVhEr2.16, AAVhEr2.30, AAVhEr2.31, AAVhEr2.36, AAVhER1.23, AAVhEr3.1, AAV2.5T , AAV-PAEC, AAV-LK01, AAV- LK02, AAV- LK03, AAV-LK04, AAV-LK05, AAV-LK06, AAV-LK07, AAV-LK08, AAV- LK09, AAV- LK10, AAV-LK11, AAV-LK12, AAV-LK13, AAV-LK14, AAV-LK15, AAV- LK16, AAV- LK17, AAV-LK18, AAV-LK19, AAV-PAEC2, AAV-PAEC4, AAV-PAEC6, AAV-PAEC7, AAV-PAEC8, AAV-PAEC11, AAV-PAEC12, AAV-2-pre-miRNA-101 , AAV-8h, AAV- 8b, AAV-h, AAV-b, AAV SM 10-2 , AAV Shuffle 100-1 , AAV Shuffle 100-3, AAV Shuffle 100-7, AAV Shuffle 10-2, AAV Shuffle 10-6, AAV Shuffle 10-8, AAV Shuffle 100- 2, AAV SM 10-1, AAV SM 10-8 , AAV SM 100-3, AAV SM 100-10, BNP61 AAV, BNP62 AAV, BNP63 AAV, AAVrh.50, AAVrh.43, AAVrh.62, AAVrh.48, AAVhu.19, AAVhu.l l, AAVhu.53, AAV4-8 / rh.64, AAVLG-9 / hu.39, AAV54.5 / hu.23, AAV54.2 / hu.22, AAV54.7 / hu.24, AAV54.1 / hu.

21. AAV54.4R / hu.27, AAV46.2 / hu.28, AAV46.6 / hu.29, AAV128.1 / hu.43, true type AAV (ttAAV), UPENN AAV 10, Japanese AAV 10 serotypes, AAV CBr-7.1, AAV CBr-7.10, AAV CBr-7.2, AAV CBr-7.3, AAV CBr- 7.4, AAV CBr-7.5, AAV CBr-7.7, AAV CBr-7.8, AAV CBr-B7.3, AAV CBr-B7.4, AAV CBr-El, AAV CBr- E2, AAV CBr-E3, AAV CBr-E4, AAV CBr-E5, AAV CBr-e5, AAV CBr-E6, AAV CBr-E7, AAV CBr-E8, AAV CHt-1 , AAV CHt-2, AAV CHt-3, AAV CHt- 6.1, AAV CHt-6.10, AAV CHt-6.5, AAV CHt-6.6, AAV CHt-6.7, AAV CHt-6.8, AAV CHt- Pl, AAV CHt-P2, AAV CHt-P5, AAV CHt-P6, AAV CHt-P8, AAV CHt-P9, AAV CKd-1, AAV CKd-10, AAV CKd-2, AAV CKd-3, AAV CKd-4, AAV CKd-6, AAV CKd-7, AAV CKd-8, AAV CKd-Bl, AAV CKd-B2, AAV CKd-B3, AAV CKd-B4, AAV CKd-B5, AAV CKd-B6, AAV CKd-B7, AAV CKd-B8, AAV CKd-Hl, AAV CKd-H2, AAV CKd-H3, AAV CKd-H4, AAV CKd- H5, AAV CKd-H6, AAV CKd-N3, AAV CKd-N4, AAV CKd- N9, AAV CLg-Fl, AAV CLg-F2, AAV CLg-F3, AAV CLg-F4, AAV CLg-F5, AAV CLg- F6, AAV CLg-F7, AAV CLg-F8, AAV CLv-1, AAV CLvl-1, AAV Clvl-10, AAV CLvl-2, AAV CLv-12, AAV CLvl-3, AAV CLv-13, AAV CLvl-4, AAV Clvl-7, AAV Clvl-8, AAV Clvl-9, AAV CLv-2, AAV CLv-3, AAV CLv-4, AAV CLv-6, AAV CLv-8, AAV CLv-Dl, AAV CLv-D2, AAV CLv-D3, AAV CLv-D4, AAV CLv-D5, AAV CLv-D6, AAV CLv-D7, AAV CLv-D8, AAV CLv-El, AAV CLv-Kl, AAV CLv-K3, AAV CLv-K6, AAV CLv-L4, AAV CLv-L5, AAV CLv-L6, AAV CLv-Ml, AAV CLv-Ml 1, AAV CLv-M2,-246-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENTAAV CLv-M5, AAV CLv-M6, AAV CLv-M7, AAV CLv-M8, AAV CLv-M9, AAV CLv- Rl, AAV CLv-R2, AAV CLv-R3, AAV CLv-R4, AAV CLv-R5, AAV CLv-R6, AAV CLv- R7, AAV CLv-R8, AAV CLv-R9, AAV CSp-1, AAV CSp-10, AAV CSp-11, AAV CSp-2, AAV CSp-3, AAV CSp-4, AAV CSp-6, AAV CSp-7, AAV CSp-8, AAV CSp-8.10, AAV CSp-8.2, AAV CSp-8.4, AAV CSp-8.5, AAV CSp-8.6, AAV CSp-8.7, AAV CSp-8.8, AAV CSp-8.9, AAV CSp-9, AAV.hu.48R3. AAV.VR-355, AAV3B, AAV4. AAV5, AAVF1 / HSC1, AAVF11 / HSC11. AAVF12 / HSC12, AAVF13 / HSC13, AAVF14 / HSC14, AAVF15 / HSC15, AAVF16 / HSC16, AAVF17 / HSC17, AAVF2 / HSC2, AAVF3 / HSC3, AAVF4 / HSC4, AAVF5 / HSC5, AAVF6 / HSC6, AAVF7 / HSC7, AAVF8 / HSC8, and / or AAVF9 / HSC9, 7m8, SparklOO, AAVMYO and variants thereof), SpCas9, SaCas9, FnCasl2a, LbCasl2a, AcCasl2a, Cast 3b, APOBEC1, E. coli TadA, Moloney Murine Leukemia Virus Reverse Transcriptase (M-MLV RT), HLA-A, HLA-B, HLA-C, HLA-E, HLA-L, HLA-J, HLA-K, HLA-H, HLA-G, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, and HLA-DR.

8. The molecule of claim 1, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest has an amino acid sequence having at least 85% sequence identity to the amino acid sequence selected from any one of SEQ ID NOs: 63, 64. 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28. 29, 30, 31, 32, 33, 34, 35, 36, or 37.

9. The molecule of claim 8, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest has an amino acid sequence selected from any one of SEQ ID NOs: 63, 64, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, or 37.

10. The molecule of claim 8, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest has the amino acid sequence of SEQ ID NO: 63.-247-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT11. The molecule of claim 8, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest has the amino acid sequence of SEQ ID NO: 64.

12. The molecule of claim 1, wherein the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest is an effector peptide or molecule capable of eliciting an autoimmune response in a subject.

13. The molecule of claim 12, wherein the effector peptide or molecule is an allergen.

14. The molecule of claim 1, wherein the molecule comprises the Fc polypeptide domain.

15. The molecule of claim 14, wherein the Fc polypeptide domain comprises any one, or any combination of L234A, L235A, L234F, L235E, P329G, P331S, N297A, N297G, N297Q, G236A, A330S, S239D, I332E, S267E, H268F, S324T, Y296W, T299A, V308P, H310A, R409K, Y435H, T307A, T309A, T309K, K322A, K326W, K334W, K326A, K334A, G237A, P238S, and H268A mutations, according to EU numbering, and as compared to SEQ ID NO: 65, 66, 67, or 68.

16. The molecule of claim 14, wherein: the Fc polypeptide domain is an effectorless Fc polypeptide domain ; the Fc polypeptide domain does not bind, or has reduced affinity, to FcRn; the Fc polypeptide domain is an effectorless Fc polypeptide domain, and wherein the Fc polypeptide domain does not bind, or has reduced affinity, to FcRn; and / pr the Fc polypeptide domain enhances antigen presentation on the surface of the cell.

17. The molecule of claim 16, wherein the cell is a thymic cell.

18. The molecule of claim 1, wherein the molecule does not comprise an Fc polypeptide domain.

19. The molecule of claim any one of claims 14-17, wherein:-248-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT the Trop2 targeting domain is conjugated to the N-terminus of Fc polypeptide domain, and the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest, is conjugated to a C-terminus of the Fc polypeptide domain; or the Trop2 targeting domain is conjugated to the C-terminus of Fc polypeptide domain, and the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest, is conjugated to the N-terminus of the Fc polypeptide domain.

20. The molecule of any one of claims 1-19, wherein the Trop2 targeting domain and the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest, are linked by a linker.

21. The molecule of claim 20, wherein the linker is a peptide linker.

22. The molecule of any one of claims 1-21, wherein the Trop2 targeting domain and the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest, are directly conjugated.

23. A molecule comprising: a) a Trop2 targeting domain that binds to Trop2 on a thymic cell, a splenic cell, a dendritic cell, or a B cell, wherein the Trop2 targeting domain binds to: the intracellular domain of Trop2, such as to the amino acid sequence of SEQID NO: 40, SEQ ID NO: 41, or SEQ ID NO: 42; the extracellular domain of Trop2; or an epitope on Trop2 that comprises residues:R318, K319, E320, P321, S322, and L323, as compared to SEQ ID NO: 38; or E304, L305, K306, E307, L308, G309, E310, M311, R312, S313, E314, P315,S316, and L317, as compared to SEQ ID NO: 39; b) an antigen that is at least 85% identical to proinsulin fragment 57-87 or proinsulin fragment 57-94; and c) optionally an Fc polypeptide domain.-249-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT24. The molecule of claim 23, wherein the thymic cell is a medullary thymic epithelial cell (mTEC), a mimetic mTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, a junction thymic epithelial cell (jTEC), a thymic progenitor epithelial cell (TPEC), a proliferating TPEC, a thymic epithelial cell (TEC), a proliferating TEC, a cortical thymic epithelial cell (cTEC), a proliferating cTEC, or a proliferating mTEC.

25. The molecule of claim 24, wherein the mimetic mTEC is a basal (skin / lung) mTEC, an enterocyte / hepatocyte mTEC, a ciliated mTEC, an ionocyte mTEC, a keratinocyte mTEC, a microfold mTEC, a muscle mTEC, a neuroendocrine mTEC, a parathyroid mTEC, a secretory mTEC, a thyroid mTEC, or a tuft mTEC.

26. The molecule of any one of claims 23-25, wherein the Trop2 targeting domain is an antibody, or an antigen-binding fragment thereof.

27. The molecule of claim 23, wherein the proinsulin fragment 57-87 comprises the amino acid sequence of SEQ ID NO: 63.

28. The molecule of claim 23, wherein the proinsulin fragment 57-94 comprises the amino acid sequence of SEQ ID NO: 64.

29. The molecule of any one of claims 23-28, wherein the molecule comprises the Fc polypeptide domain.

30. The molecule of claim 29, wherein the Fc polypeptide domain comprises any one, or any combination of L234A, L235A, L234F, L235E, P329G, P331S, N297A, N297G, N297Q, G236A, A330S, S239D, I332E, S267E, H268F, S324T, Y296W, T299A. V308P, H310A, R409K, Y435H, T307A, T309A, T309K, K322A, K326W, K334W, K326A, K334A, G237A, P238S, and H268A mutations, according to EU numbering, and as compared to SEQ ID NO: 65, 66, 67, or 68.

31. The molecule of claims 29 or 30, wherein: the Fc polypeptide domain is an effectorless Fc polypeptide domain;-250-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT the Fc polypeptide domain does not bind, or has reduced affinity, to FcRn; the Fc polypeptide domain is an effectorless Fc polypeptide domain, and wherein the Fc polypeptide domain does not bind, or has reduced affinity, to FcRn; and / pr the Fc polypeptide domain enhances antigen presentation on the surface of a cell.

32. The molecule of claim 31, wherein the cell is a thymic cell.

33. The molecule of claim 23, wherein the molecule does not comprise an Fc polypeptide domain.

34. The molecule of claim 23, wherein: the Trop2 targeting domain is conjugated to the N-terminus of Fc polypeptide domain, and the proinsulin fragment 57-87 or the proinsulin fragment 57-94, is conjugated to a C-terminus of the Fc polypeptide domain; or the Trop2 targeting domain is conjugated to the C-terminus of Fc polypeptide domain, and the proinsulin fragment 57-87 or the proinsulin fragment 57-94, is conjugated to the N- terminus of the Fc polypeptide domain.

35. The molecule of any one of claims 23-34, wherein the Trop2 targeting domain and the proinsulin fragment 57-87 or the proinsulin fragment 57-94, are linked by a linker.

36. A dimer molecule comprising a first molecule and a second molecule, wherein: the first molecule is a molecule of any one of claims 1-35; and the second molecule is a molecule of any one of claims 1-35.

37. The dimer molecule of claim 36, wherein the first polypeptide and the second polypeptide are the same polypeptides (homodimer) or different polypeptides (heterodimer).

38. A pharmaceutical composition comprising the molecule of any one of claims 1-35, or the dimer molecule of any one of claims 36-37.

39. A method of modulating a cell, or a plurality of cells, the method comprising contacting the cell with the molecule of any one of claims 1-35, the dimer molecule of any one of claims 36-37, or the pharmaceutical composition of claim 38.-251-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT40. A method of modulating a thymic cell, or a plurality of thymic cells, the method comprising contacting the thymic cell, or the plurality of thymic cells, with the molecule of any one of claims 1-35, the dimer molecule of any one of claims 36-37, or the pharmaceutical composition of claim 38.

41. The method of claim 40, wherein the method further comprises the thymic cell, or the plurality of thymic cells, internalizing the molecule of any one of claims 1-35, the dimer molecule of any one of claims 36-37, to produce a modulated thymic cell, or a plurality of modulated thymic cells, comprising the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest.

42. The method of claim 41, wherein the modulated thymic cell, or plurality of modulated thymic cells, comprises any one of the antigens of interest of any one of claims 1-35 on the membrane surface of the modulated thymic cell.

43. The method of any one of claims 40-42, wherein the thymic cell is a medullary thymic epithelial cell (niTEC), a mimetic niTEC, an AIRE+ mTEC, an AIRE- mTEC, a mTEC progenitor cell, a mimetic mTEC progenitor cell, a junction thymic epithelial cell (jTEC), a thymic progenitor epithelial cell (TPEC), a proliferating TPEC, a thymic epithelial cell (TEC), a proliferating TEC, a cortical thymic epithelial cell (cTEC), a proliferating cTEC, or a proliferating mTEC.

44. A method of inducing antigen-specific Treg expansion in a subject, the method comprising administering to the subject the molecule of any one of claims 1-35, the dimer molecule of any one of claims 36-37, or the pharmaceutical composition of claim 38.

45. The method of claim 44, wherein the Treg is a thymic Treg, or a splenic Treg.

46. The method of claim 45, wherein the Treg is a CD4+FoxP3+ Treg, or a CD4+FoxP3+CD73- Treg.-252-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT47. The method of any one of claims 44-46, wherein the molecule of any one of claims 1- 44, the dimer molecule of any one of claims 45-46, or the pharmaceutical composition of claim 47 is administered to the subject systematically.

48. The method of any one of claims 44-47, wherein the method does not significantly induce antigen-specific Teff cells.

49. A method of inducing immune tolerance against an autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest, such as T cell tolerance to the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest in a subject, the method comprising administering to the subject the molecule of claim 1, thereby inducing tolerance against the antigen of interest.

50. The method of claim 49, wherein the T cell is specific against the autoimmune antigen of interest, alloimmune antigen of interest, allergic antigen of interest, inflammatory antigen of interest, or anti-drug immune response associated antigen of interest present in the molecule of claim 1.51 . The method of any one of claims 49-50, wherein the T cell is a CD4+CD8+ T cell, a CD4+ T cell, a CD8+ T cell, a CD4+FoxP3+ Treg, or a CD4+FoxP3+CD73- Treg.

52. The method of claim 49, wherein the molecule is administered to the subject systematically.

53. The method of claim 49, wherein the molecule is not administered intrathymically.

54. A method of treating or reducing an autoimmune, alloimmune, allergic, inflammatory, or anti-drag immune response in a subject, the method comprising administering the molecule of any one of claims 1-35, the dimer molecule of any one of claims 36-37, or the pharmaceutical composition of claim 38, to the subject.-253-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT55. The method of claim 54, wherein the autoimmune, alloimmune, allergic, inflammatory, or anti -drug immune response is elicited by a disorder, such as asthma, severe asthma, neutrophilic asthma, paucigranulocytic asthma, eosinophilic asthma, osteoarthritis, solid organ transplant, atopic dermatitis, eosinophilic esophagitis, dermatitis herpetiformis, chronic rhinosinusitis, chronic spontaneous urticaria, food allergy, anti-biologic drug immune response, anti-viral immune response, anti-AAV immune response, anti-adenoviral immune response, anti-retroviral immune response, anti-lentiviral immune response, and-VLP immune response, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, dementia with Lewy bodies, Duchenne muscular dystrophy, cutaneous lupus myocarditis, postmyocardial infarction syndrome, postpericardiotomy syndrome, subacute bacterial endocarditis, anti-glomerular basement membrane nephritis, interstitial cystitis, lupus nephritis, membranous glomerulonephropathy, chronic kidney disease ("CKD"), autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, antisynthetase syndrome, alopecia areata, autoimmune angioedema, autoimmune progesterone dermatitis, autoimmune urticaria, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, discoid lupus erythematosus, epidermolysis bullosa acquisita, erythema nodosum, gestational pemphigoid, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IgA disease (LAD), morphea, pemphigus, pemphigus vulgaris, hidradenitis suppuritiva, pityriasis lichenoides et varioliformis acuta, Mucha-Habermann disease, psoriasis, guttate psoriasis, erythrodermic psoriasis, plaque psoriasis, pustular psoriasis, systemic sclerosis, skin manifestation associated with systemic sclerosis,, vitiligo, Addison's disease, autoimmune polyendocrine syndrome (APS) type 1, autoimmune polyendocrine syndrome (APS) type 2, autoimmune polyendocrine syndrome (APS) type 3, autoimmune pancreatitis (AIP), diabetes mellitus type 1, autoimmune thyroiditis, Ord's thyroiditis, Graves' disease, non-radiographic axial spondyloarthropathy, autoimmune oophoritis, endometriosis, autoimmune orchitis, Sjogren's syndrome, dermatitis herpatiformis, autoimmune enteropathy, coeliac disease, Crohn's disease, immune related adverse events (irAEs) secondary to immune checkpoint inhibitors, microscopic colitis, ulcerative colitis, autoimmune thrombocytopenia, adiposis dolorosa, adult-onset Still's disease, ankylosing spondylitis, CREST syndrome, drug-induced lupus, enthesitis-related arthritis, eosinophilic fasciitis, Felty syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease (MCTD), palindromic rheumatism, Parry Romberg syndrome, Parsonage-Turner syndrome, psoriatic arthritis, reactive arthritis, relapsing polychondritis, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis,-254-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT sarcoidosis, Schnitzler syndrome, systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), dermatomyositis, fibromyalgia, inclusion body myositis, myositis, myasthenia gravis, neuromyotonia, paraneoplastic cerebellar degeneration, polymyositis, acute disseminated encephalomyelitis (ADEM), acute motor axonal neuropathy, anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis, balo concentric sclerosis, Bickerstaffs encephalitis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, Hashimoto's encephalopathy, idiopathic inflammatory demyelinating diseases, Lambert-Eaton myasthenic syndrome, multiple sclerosis, oshtoran syndrome, pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), progressive inflammatory neuropathy, restless leg syndrome, stiff person syndrome, Sydenham chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, Cogan syndrome, Graves ophthalmopathy, intermediate uveitis, ligneous conjunctivitis, Mooren's ulcer, neuromyelitis optica, opsoclonus myoclonus syndrome, optic neuritis, scleritis, Susac's syndrome, sympathetic ophthalmia, Tolosa-Hunt syndrome, autoimmune inner ear disease (AIED), Meniere's disease, Behcet's disease, eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis, granulmatosis with polyangiitis (GPA), IgA vasculitis (IgAV), Kawasaki's disease, leukocytoclastic vasculitis, lupus vasculitis, rheumatoid vasculitis, microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), polymyalgia rheumaticia, vasculitis, primary immune deficiency, Gaucher disease, Pompe disease, Fabry disease, Schindler disease, Hurler syndrome (MPS1), Tay-Sachs disease, Nieman-Pick disease, Farber lipogranulomatosis, Krabbe disease, Morquio syndrome (MPS4), mucopolysaccharidosis type VI (MPS6), Hunter syndrome (MPS2), Sanfilippo syndrome (MPS3), Sly sundrome (MPS7), hyaluronidase deficiency (MPS9), mucolipidosis type 1 (ML1), I-cell disease, mucolipidosis II (ML2), mucolipidosis III gamma (ML3C), glycogen storage disease la, glycogen storage disease lb, Wilson disease, phenylketonuria, Stargardt disease type I, myocilin-associated glaucoma, hemophilia A, hemophilia B, hereditary or acquired thrombotic thrombocytopathic purpura (TTP), von Willebrand disease, thrombocytopenia platelet autoantigen, heparin-induced thrombocytopenia, tolerance induction for AAV gene therapy, tolerance induction for ex vivo gene editing, tolerance induction for in vivo gene editing, acquired hemophilia, antiphospholipid syndrome, aplastic anemia, autoimmune lymphoproliferative syndrome, autoimmune neutropenia, autoimmune thrombocytopenic purpura, cold agglutinin disease, essential mixed cryoglobulinemia, Evans syndrome, IgG4-related diseases, pure red cell aplasia, warm autoimmune hemolytic anemia, autoimmune gastritis, celiac disease, pernicious anemia, anti-sperm antibodies, autoimmune -255-IPTS / 200142710.2DOCKET NO. ZAG-006WO PATENT polyendocrine syndrome type 1 , autoimmune poly endocrine syndrome type 2, autoimmune poly endocrine syndrome type 3, autoimmune myocarditis, cryptogenic organizing pneumonia, idiopathic pulmonary fibrosis, IgA nephropathy, post-myocardial infarction syndrome, primary biliary cholangitis, primary idiopathic dilated cardiomyopathy, anti-N- methyl-D-aspartate receptor encephalitis, autoimmune encephalitis, encephalopathy associated with autoimmune thyroid disease, episcleritis, Graves' ophthalmopathy, myelin oligodendrocyte glycoprotein disease, narcolepsy with cataplexy, cutaneous lupus erythematosus, adult-onset Still's disease, ankylosing spondylitis, juvenile arthritis, juvenile dermatomyositis, anti-neutrophil cytoplasmic antibody-associated vasculitis, polymyalgia rheumatic, purpura rheumatic, Takayasu arteritis, graft versus host disease (GVHD), transplant, and xenotransplantation.

56. The method of any one of claims 54-55, wherein the molecule of any one of claims 1- 35, the dimer molecule of any one of claims 36-37, or the pharmaceutical composition of claim 38 is administered to the subject systematically.-256-IPTS / 200142710.2

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