Antibodies binding to vista at acidic ph

Abstract

To provide antibodies specifically binding to VISTA and their use in cancer treatment.SOLUTION: The present invention provides antibodies specifically binding to the V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) at acidic pH. In some embodiments, the antibodies bind specifically to human VISTA at acidic pH, but do not significantly bind to human VISTA at neutral or physiological pH.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] This application relates to antibodies that specifically bind to V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) at acidic pH and their use in cancer treatment. [Background technology]

[0002] V-domain Ig-containing suppressor of T-cell activation, or VISTA, is a co-inhibitory member of the B7 family of immune receptors expressed by myelomonocytic cells and other leukocytes. However, the mechanism by which VISTA suppresses immune responses is not well understood.

[0003] The present inventors have found that, unlike other known immune receptors, VISTA selectively engages and functions with its counterreceptor at acidic pH, but has very low activity at physiological pH (e.g., 7.3-7.4). Therefore, VISTA may suppress immune responses in acidic microenvironments, such as tumor beds or sites of inflammation, without interfering with cells circulating in the blood or retaining in non-inflamed, non-acidic tissues. Additionally, the present inventors have found that anti-VISTA antibodies can be engineered to selectively bind to VISTA at acidic pH, but exhibit little or no binding at physiological pH, similar to the acidic pH selectivity of VISTA itself. Such acidic pH-selective antibodies may offer desirable properties for treating diseases such as cancer, compared to antibodies that bind to VISTA at physiological pH. Summary of the Invention

[0004] The present disclosure relates to antibodies that specifically bind to the extracellular domain (ECD) of VISTA, such as human VISTA ("hVISTA" or "huVISTA"), at acidic pH (e.g., under acidic conditions). The present disclosure also relates to antibodies that specifically bind to the extracellular domain (ECD) of VISTA, such as hVISTA, at acidic pH, but show little or no binding at neutral or physiological pH. The inventors herein recognized that the hVISTA-ECD amino acid sequence contains many conserved and non-conserved histidine residues, and that the frequency of histidine residues in the ECD of VISTA is very high compared to other B7 family members and other immunoglobulin superfamily members. (See Figures 1A and 1B.) The amino acid histidine has a pKa of approximately 6.5 in solution. This means that at pH 6.5 or lower, histidine residues in proteins are often protonated and therefore positively charged, but become increasingly unprotonated and charge-neutral at pHs higher than 6.5. Because tumor microenvironments and inflamed tissues are often acidic, VISTA proteins found in these microenvironments may have at least partially protonated histidine residues. As discussed herein, the inventors hypothesized that histidine protonation may affect the conformation, surface structure, and / or charge density of VISTA, which in turn may generate pH-specific or pH-selective epitopes for both receptor-ligand interactions and antibody binding. Targeting VISTA with antibodies that bind at acidic pH but not at neutral or physiological pH may prevent target-mediated pharmacokinetics by circulating and lymphoid organ-resident myelomonocytic cells and improve antibody PK, receptor occupancy, and activity in the tumor microenvironment. Acidic pH selective antibodies can also improve the specificity of VISTA antibodies to target cells within the tumor rather than in the circulation for therapeutic modalities such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and delivery of payloads (antibody-drug conjugates).

[0005] Color versions of some of the drawings are provided in priority U.S. Provisional Patent Application No. 62 / 636,746, filed February 28, 2018. The priority application file was made available upon publication of this application, and copies of the color drawing(s) will be provided by the U.S. Patent and Trademark Office upon request, upon payment of the necessary fee. [Brief explanation of the drawings]

[0006] [Figure 1A] 1 shows that the extracellular domain of VISTA contains a very high frequency of histidine residues, many of which are conserved, and at least some of which can participate in receptor-ligand binding. Also shown is a graph of immunoglobulin domain-containing proteins, with the number of amino acid residues in the extracellular domain of each protein plotted on the X-axis and the frequency of histidine residues in the extracellular domain of each protein plotted on the Y-axis. The size of each data point corresponds to the total number of histidine residues in the extracellular domain of each protein. [Figure 1B] This figure shows that the extracellular domain of VISTA contains a very high frequency of histidine residues, many of which are conserved, and at least some of which may be involved in receptor-ligand binding. Also shown are aligned amino acid sequences of the extracellular domains of human, cynomolgus macaque, and mouse VISTA. The signal peptide (Sig) and transmembrane domain (TMD) sequence positions are marked. Histidine residues conserved across all three species are shown in bold and underlined, while histidine residues conserved across humans and cynolmogus macaques are shown in bold only. [Figure 1C]

[0023] Figure 1 shows that the extracellular domain of VISTA contains a very high frequency of histidine residues, many of which are conserved, and at least some of which may be involved in receptor-ligand binding. Also shown is a model of the three-dimensional structure of a human VISTA immunoglobulin domain. Histidine residues are shown as ball-and-stick traces. [Figure 2A]

[0023] Figure 1 shows a model for how histidine residues in the extracellular domain of VISTA confer counter-receptor selectivity at acidic pH but not at physiological pH. It also shows that the absence and presence of protonation of the pyrrole ammonium group (NH) of the histidine residues are in equilibrium. The pKa of histidine in solution is 6.5. This indicates that histidine residues are more likely to be protonated, and therefore more likely to be positively charged, at pH 6.5 and lower than at higher pHs. [Figure 2B]

[0023] Figure 1 shows a model in which histidine residues in the extracellular domain of VISTA confer counter-receptor selectivity at acidic but not physiological pH. Also shown is a model in which VISTA selectively engages P-selectin glycoprotein ligand 1 (PSGL-1) or other counter-receptors and ligands ("VISTA-R") at acidic pH. Thus, antibodies that bind to the extracellular domain of VISTA at acidic but not physiological pH may be important for inhibiting or modulating VISTA activity. [Figure 3] Figure 1 shows the levels of VISTA surface expression (mean fluorescence intensity (MFI) of anti-VISTA antibody staining) on ​​tumor-infiltrating macrophages, dendritic cells, neutrophils, CD4+ effector T cells, CD4+ regulatory T cells, CD8+ T cells, natural killer (NK) cells, and B cells. VISTA is expressed on numerous tumor-infiltrating leukocytes, particularly myeloid cells. The tumor microenvironment is often acidic, allowing VISTA to engage with counterreceptors and ligands. [Figure 4A]This figure shows that VISTA selectively binds to leukocytes and PSGL-1 at acidic pH, but exhibits little or no binding at neutral pH, and this binding can be blocked by anti-VISTA antibodies. The left side of Figure 4A shows representative histograms of fluorescently conjugated recombinant VISTA multimers binding to activated human CD4+ T cells. Filled histograms, ranging from darker to lighter gray, indicate binding at pH 7.0, 6.5, 6.4, 6.3, 6.1, and 6.0. Some histograms are labeled with their corresponding pH. A non-VISTA control multimer, which binds at pH 6.0, is shown as an open histogram. The right side graphs the average MFI of VISTA (circles) and control (triangles) multimers binding to activated human CD4+ T cells from two donors at various pHs. [Figure 4B] Figure 4B shows that VISTA selectively binds to leukocytes and PSGL-1 at acidic pH, but little or no binding at neutral pH, and this binding can be blocked by anti-VISTA antibodies. Figure 4B shows representative histograms of recombinant VISTA multimer binding to peripheral blood mononuclear cells (PBMCs) at pH 6.0 and pH 7.4. The filled histograms, from darker to lighter gray, show binding to CD19+ B cells, CD4+ T cells, CD8+ T cells, CD56+ NK cells, and CD14+ monocytes at pH 6.0. The unfilled, solid-border and dotted-border histograms show binding to PBMC lymphocytes and monocytes, respectively, at pH 7.4. [Figure 4C]Figure 4C shows that VISTA selectively binds to leukocytes and PSGL-1 at acidic pH, but exhibits little or no binding at neutral pH, and that this binding can be blocked by anti-VISTA antibodies. Figure 4C shows binding of representative recombinant VISTA multimers to activated human CD4+ T cells in the presence of anti-VISTA blocking antibodies (squares) or a non-VISTA-specific isotype-matched control antibody (circles). Antibody concentrations are plotted on a logarithmic scale. Nonlinear regression curves are also shown. Triangles indicate background signal from activated human CD4+ T cells that were not stained with recombinant VISTA multimers. [Figure 4D] This figure shows that VISTA selectively binds to leukocytes and PSGL-1 at acidic pH, but little or no binding at neutral pH, and this binding can be blocked by anti-VISTA antibodies. Also shown are representative two-dimensional flow cytometry plots of recombinant VISTA multimers binding at pH 6.0 to heparan sulfate-deficient Chinese hamster ovary (CHO) cells (strain pGSD-677, American Type Culture Collection) transfected to express human PSGL-1. Multimer binding was performed in the presence and absence of the anti-VISTA blocking antibodies shown in Figure 4C. Cells left unstained with recombinant VISTA multimers are shown as controls. PSGL-1 antibody staining is plotted on the Y-axis, and VISTA multimer staining is plotted on the X-axis. [Figure 4E] Representative histograms of recombinant mouse VISTA-Fc fusion protein binding to mouse splenocytes at pH 6.0 and pH 7.4 are shown. Filled histograms, from darker to lighter gray, show binding to CD8+ T cells, CD11b+ myeloid cells, and CD4+ T cells at pH 6.0. Open histograms show binding to whole splenocytes at pH 7.4. [Figure 5A-5B](A) and (B) show that VISTA preferentially mediates T cell suppression and cell-cell adhesion at acidic pH, and both effects can be reversed by anti-VISTA blocking antibodies. (A) Representative cell-cell conjugate formation at pH 6.0 and 7.0 between 293T cells expressing hVISTA or a vector control (plotted on the y-axis) and CHO cells endogenously expressing cell surface heparan sulfate on the x-axis. (B) Graph showing the frequency of cell-cell conjugates formed between the same cells at pH 6.0 in the presence of an anti-VISTA blocking antibody, an anti-VISTA non-blocking antibody, or an isotype-matched non-VISTA-specific control antibody. [Figure 5C-5D] (C) shows that VISTA preferentially mediates T cell suppression and cell-cell adhesion at acidic pH, and both effects can be reversed by anti-VISTA blocking antibodies. (D) Representative plots of luciferase activity produced by Jurkat (a human T cell line) cells expressing an NFkB luciferase reporter after co-culture with 293T cells ("artificial antigen-presenting cells") expressing hVISTA and a single-chain variable fragment of the anti-human T cell receptor agonist antibody OKT3 at various pHs. Anti-VISTA blocking antibodies (squares) or an isotype-matched non-VISTA-specific control antibody (circles) were added to the co-cultured cells. (D) The data shown in Figure 5A are plotted as the fold increase in luciferase signal with anti-VISTA antibody treatment compared to the control ("effect size"). [Figure 6A] Figure 6A shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6A shows the colocalization of VISTA, Rab5 (an early endosome marker), Rab7 (a late endosome marker), and Rab11 (a recycling endosome marker) in 293T cells expressing human VISTA. [Figure 6B]Figure 6B shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6B shows the colocalization of VISTA and Rab11 within human monocytes. Intracellular VISTA is colocalized with Rab11+ recycling endosomes. A non-VISTA-binding control antibody ("cAb") of the same isotype as the VISTA antibody shows no detectable binding to monocytes. [Figure 6C] Figure 6C shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6C shows the binding of three anti-VISTA antibodies to recombinant VISTA at pH 7.4 (black), 6.7 (darker gray), and 6.7 (lighter gray). [Figure 6D] Figure 6D shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface via endosomal trafficking. Figure 6D shows the sensitivity of VISTA-expressing acute myeloid leukemia (AML) cell lines to killing by the same anti-VISTA antibodies 1 (inverted triangle), 2 (circle), and 3 (square) with cathepsin B-sensitive linkers and cytotoxic payloads, or a non-VISTA-specific control antibody (triangle). Cell viability (CellTiter-Glo LU) is plotted on the Y-axis, and antibody concentration is plotted on the X-axis. [Figure 6E] Figure 6E shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6E compares hVISTA binding of anti-VISTA antibody 3 to hVISTA binding of an engineered variant ("VISTA mAb3c") that does not exhibit poor binding at acidic pH. [Figure 6F]Figure 6F shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6F shows an antibody-drug-conjugate assay comparing the potency of anti-VISTA antibodies 3 (squares) and 3c (diamonds). [Figure 6G] Figure 6G shows that VISTA can be found in intracellular endosomes, particularly Rab11+ recycling endosomes, and that VISTA can be recycled to and from the cell surface by endosomal trafficking. Figure 6G shows a scheme of endosomal trafficking, in which VISTA is recycled to and from the cell surface by early endosomes and recycling endosomes. [Figure 7A] This figure shows how the anti-VISTA antibody variant library was designed and screened for acidic pH-selective antibodies. Figure 7A shows the amino acid substitutions made in the VH CDR3 of the anti-human VISTA antibody clone P1-061029 (abbreviated as '029) to generate the '029 library for screening. To potentially improve binding to the histidine-rich region of VISTA at acidic pH, the library allowed substitution of the negatively charged amino acids aspartic acid and glutamic acid and pH-sensitive histidine. X = H, D, or E. Bracketed sequences were removed from the synthesis to avoid introducing instability. A total of 647 unique sequences of P1-061029 HCDR3 with one or two mutations were synthesized. [Figure 7B] Figure 7B shows how the anti-VISTA antibody variant library was designed and screened for acidic pH-selective antibodies. Figure 7B shows the procedure for iteratively screening the '029 library to select acidic pH-selective antibody variants. R indicates selection round. [Figure 7C]Figure 7A shows how the anti-VISTA antibody mutant library was designed and screened to obtain acidic pH-selective antibodies. Figure 7C shows representative two-dimensional flow cytometry plot data showing the mutant pool after nine rounds of selection. VISTA binding is plotted on the Y-axis, and mutant antibody expression is plotted on the X-axis. Binding data at various antibody concentrations and pHs are shown. [Figure 7D] Figure 7D shows how the anti-VISTA antibody variant library was designed and screened for acidic pH-selective antibodies. Figure 7D shows a diagram of the binding of P1-061029 and its progeny clones to human VISTA at pH 6.0 and 7.4. [Figure 7E] Figure 7E shows how the anti-VISTA antibody variant library was designed and screened for acidic pH-selective antibodies. Figure 7E shows a diagram of the dissociation rates of P1-061029 and its progeny clones against human VISTA at pH 6.0. [Figure 7F] Figure 7F shows how the anti-VISTA antibody variant library was designed and screened for acidic pH-selective antibodies. Figure 7F shows SPR binding data for antibodies P1-068761, P1-068767, and P1-061029 against human VISTA at pH 6.0 and pH 7.4. [Figure 8A-8B]Figure 8 shows the pH-selective cell binding, blocking, and effector activity of VISTA antibodies P1-068761 and P1-068767. Panels A and B show the mean fluorescence emission intensity of the acidic pH-selective antibodies P1-068761 (Figure 8A) and P1-068767 (Figure 8B) binding to Raji cells ectopically expressing human VISTA. Cells were stained at approximately pH 6.0 (circles; topmost curve in Figure 8A), 6.1 (squares; third topmost curve), 6.2 (triangles; second topmost curve), 6.4 (inverted triangles; fourth topmost curve near the pH 6.1 curve), 6.6 (diamonds; fourth bottommost curve), 7.0 (circles; third bottommost curve), 7.2 (squares; second bottommost curve), and 8.1 (open triangles; lowest bottom curve in Figure 8A). Binding was detected with a fluorescently conjugated anti-human IgG secondary antibody. [Figure 8C] Figure 8C shows the pH-selective cell binding, blocking, and effector activity of VISTA antibodies P1-068761 and P1-068767. Figure 8C shows the binding of 3125 ng / mL P1-068767 (circles) and an isotype-matched nonspecific control antibody (triangles) to Raji cells ectopically expressing human VISTA at various pHs. "pH50," the pH at which 50% of P1-068767 binding is lost, is approximately 6.6. [Figure 8D] Figure 8D shows the pH-selective cell binding, blocking, and effector activity of VISTA antibodies P1-068761 and P1-068767. Figure 8D shows the mean fluorescence intensity (MFI) of binding to human monocytes by an isotype-matched nonspecific control antibody (filled and open circles, pH 7.0 and 6.0, respectively), anti-VISTA mAb2 ("Control"; see Figure 6C; filled and open squares, pH 7.0 and 6.0, respectively), P1-068761 (filled and open triangles, pH 7.0 and 6.0, respectively), and P1-068767 (filled and open inverted triangles, pH 7.0 and 6.0, respectively). Binding was detected with a fluorescently conjugated anti-human IgG secondary antibody. [Figure 8E]Figure 8E shows the pH-selective cell binding, blocking, and effector activity of VISTA antibodies P1-068761 and P1-068767. At pH 6.0, recombinant VISTA multimer binding to activated human CD4+ T cells was equivalently blocked by P1-061029 (squares), P1-068761 (triangles), and P1-068767 (inverted triangles), whereas a non-VISTA-specific control antibody (circles) did not block VISTA binding. [Figure 8F] Figure 8F shows pH-selective cell binding, blocking, and effector activity of VISTA antibodies P1-068761 and P1-068767. Figure 8F shows that at physiological pH, the potency of P1-068761 (triangles) and P1-068767 (inverted triangles) in mediating antibody-dependent cellular cytotoxicity (ADCC) was reduced. P1-061029 (squares), a non-VISTA-specific positive control antibody (circles), and a non-VISTA-specific negative control antibody (diamonds) are also shown. NK cell-specific lysis of target cells as a percentage of total target cells is plotted on the Y-axis, and antibody concentration is plotted on the X-axis. Nonlinear regression curves are also shown. [Figure 9] Figure 6C shows enhanced pharmacokinetics (PK) of acidic pH-selective anti-VISTA antibodies in cynomolgus monkeys. The figure shows serum antibody concentrations over time in cynomolgus monkeys treated with VISTA antibody 2 ("control," circles, see Figure 6C), VISTA antibody 3 ("acidic pH-sensitive," squares, see Figure 6C), or P1-068767 (triangles). [Figure 10A] Figure 10 shows the effect of mutations on binding in acidic pH selective anti-VISTA antibodies '761 and '767. Figure 10A shows kinetic binding data for P1-068761 revertants at pH 7.4, pH 6.7, and pH 6.0, and the location of the backmutations relative to P1-068761. [Figure 10B]Figure 10B shows the effect of mutations on binding in acidic pH selective anti-VISTA antibodies '761 and '767. Figure 10B shows kinetic binding data for P1-068761 revertants at pH 7.4, pH 6.7, and pH 6.0, and the position of the backmutations relative to P1-068767. [Figure 11A] Figure 11 shows epitope binning and mapping of various anti-VISTA antibodies: Figure 11A shows VISTA epitope competition for P1-068761 and P1-068767 compared to P1-061029 and a VISTA antibody control. [Figures 11B-11C] Figure 11B shows epitope binning and mapping of various anti-VISTA antibodies. Figures 11B and 11C show a graphical representation of all epitope residues of the blocking hVISTA antibodies listed in Table 14 (Figure 11B) compared to the non-blocking hVISTA antibody (mAb1; Figure 11C). Amino acid residues 66 (H) and 162 (A) are shown to indicate molecular orientation. Histidine residues are in gray, and epitope residues are in black. [Figures 12A-12C] Figure 12 shows the following imaging capillary isoelectric focusing (icIEF) data: Figure 12A: P1-061029, Figure 12B: P1-068761, and Figure 12C: P1-068767. The isoelectric points of the major species (main pI) as well as pI markers are shown. [Figure 13A] Figure 13A shows an alignment of the variable regions of '029 and '015 progeny clones. Figure 13A shows an alignment of the amino acid sequences of the variable regions of '029 and its progeny clones. [Figure 13A-1] This is a continuation of Figure 13A. [Figure 13B] Figure 13B shows an alignment of the variable regions of '029 and '015 progeny clones. Figure 13B shows an alignment of the amino acid sequences of the variable regions of '015 and its progeny clones. DETAILED DESCRIPTION OF THE INVENTION

[0007] definition In this application, the use of "or" means "and / or" unless stated otherwise. In the context of a multiple dependent claim, the use of "or" refers to only one or more of the preceding independent or alternative dependent claims. The terms "comprising," "including," and "having" can be used interchangeably herein. According to the present invention, an "isolated" molecule is one that has been removed from its natural environment. As such, the term "isolated" does not necessarily reflect the extent to which the molecule has been purified.

[0008] The term "polypeptide" refers to a polymer of amino acid residues and is not limited to a minimum length. A "protein" may comprise one or more polypeptides. Such polymers of amino acid residues may contain natural or unnatural amino acid residues, including, but not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are encompassed by this definition. These terms also include post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, and phosphorylation. Furthermore, for purposes of the present invention, "polypeptide" or "protein" refer to polypeptides or proteins, respectively, that contain modifications, such as deletions, additions, and substitutions (generally conservative in nature), to the native sequence, so long as the protein maintains the desired activity. Such modifications may be deliberate, such as by site-directed mutagenesis, or may be accidental, such as due to mutations of hosts producing the protein or errors due to PCR amplification. A protein may comprise two or more polypeptides.

[0009] "VISTA" is an abbreviation for V-domain immunoglobulin-containing suppressor of T-cell activation and is a member of the B7 family of immune checkpoint regulators. VISTA is also known as PD-1 homolog (PD1H), B7-H5, C10orf54, differentiation of ESC-1 (Dies-1), platelet receptor Gi24 precursor, and death domain 1 alpha (DD1α). The term "hVISTA" or "huVISTA" refers herein to the human VISTA protein. The amino acid sequence of hVISTA, including the signal peptide, is provided in SEQ ID NO: 1, and the sequence without the signal peptide is provided in SEQ ID NO: 2. (See Sequence Listing below.) The extracellular domain of VISTA, or "ECD," or "VISTA-ECD," refers to the portion of the VISTA protein located in the extracellular space, which, in the case of hVISTA, includes amino acids 1-162 of SEQ ID NO: 2. (See also FIG. 1B.) The "IgV domain" portion of hVISTA comprises residues 5-135 of SEQ ID NO:2.

[0010] The term "leader peptide" or "leader sequence" refers to a sequence of amino acid residues located at the N-terminus of a polypeptide that facilitates secretion of the polypeptide from mammalian cells. The leader sequence is cleaved to form the mature protein once the polypeptide is exported from the mammalian cell. Leader sequences can be natural or synthetic, and can be heterologous or homologous to the protein to which they are attached.

[0011] The term "antibody" or "Ab" is used herein in the broadest sense and encompasses various antibody structures, including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity. As used herein, this term refers to a molecule comprising at least the complementarity-determining regions (CDRs) 1, 2, and 3 of a heavy chain and at least the CDRs 1, 2, and 3 of a light chain, and capable of binding to an antigen. The term antibody includes fragments capable of binding to an antigen, such as, but not limited to, Fv, single-chain Fv (scFv), Fab, Fab', and (Fab')2. The term "antibody" also includes, but is not limited to, chimeric antibodies, humanized antibodies, human antibodies, and antibodies of various species, such as mouse and cynomolgus monkey.

[0012] The term "heavy chain" or "HC" refers to a polypeptide comprising at least a heavy chain variable region, with or without a leader sequence. In some embodiments, a heavy chain comprises at least a portion of a heavy chain constant region. The term "full-length heavy chain" refers to a polypeptide comprising a heavy chain variable region and a heavy chain constant region, with or without a leader sequence, and with or without a C-terminal lysine (K).

[0013] The term "heavy chain variable region" or "VH" refers to a region comprising heavy chain complementarity determining region (CDR) 1, heavy chain framework region (FR) 2, CDR2, FR3, and CDR3. Additionally, in some embodiments, a heavy chain variable region comprises at least a portion of FR1 and / or at least a portion of FR4. As specified below, in some embodiments, heavy chain CDR1 comprises residues 26-35 of a VH SEQ ID NO: herein, heavy chain CDR2 comprises residues 50-66 of a VH SEQ ID NO: herein, and heavy chain CDR3 comprises residues 99-110 of a VH SEQ ID NO: herein. In other embodiments, where specified, heavy chain CDR1 corresponds to Kabat residues 31-35, heavy chain CDR2 corresponds to Kabat residues 50-65, and heavy chain CDR3 corresponds to Kabat residues 95-102. See, e.g., Kabat Sequences of Proteins of Immunological Interest (1987 and 1991, NIH, Bethesda, Md.). In some embodiments, the heavy chain CDRs are as specified herein, such as in the Sequence Listing below or Table 2.

[0014] The term "light chain" or "LC" refers to a polypeptide comprising at least a light chain variable region, with or without a leader sequence. In some embodiments, a light chain comprises at least a portion of a light chain constant region. The term "full-length light chain" refers to a polypeptide comprising a light chain variable region and a light chain constant region, with or without a leader sequence.

[0015] The term "light chain variable region" or "VL" refers to a region comprising light chain CDR1, FR2, HVR2, FR3, and HVR3. In some embodiments, the light chain variable region also comprises FR1 and / or FR4. As specified below, in some embodiments, light chain CDR1 comprises residues 24-35 of a VL SEQ ID NO: herein, light chain CDR2 comprises residues 51-57 of a VL SEQ ID NO: herein, and light chain CDR3 comprises residues 90-98 of a VL SEQ ID NO: herein. In other embodiments, where specified, light chain CDR1 corresponds to Kabat residues 24-34, light chain CDR2 corresponds to Kabat residues 50-56, and light chain CDR3 corresponds to Kabat residues 89-97. See, e.g., Kabat Sequences of Proteins of Immunological Interest (1987 and 1991, NIH, Bethesda, MD). In some embodiments, the light chain CDRs are as specified herein, such as in the sequence listing.

[0016] A "chimeric antibody" refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, with the remainder of the heavy and / or light chain derived from a different source or species. In some embodiments, a chimeric antibody refers to an antibody comprising at least one variable region derived from a first species (mouse, rat, cynomolgus monkey, etc.) and at least one constant region derived from a second species (human, cynomolgus monkey, etc.). In some embodiments, a chimeric antibody comprises at least one mouse variable region and at least one human constant region. In some embodiments, a chimeric antibody comprises at least one cynomolgus monkey variable region and at least one human constant region. In some embodiments, all of the variable regions of a chimeric antibody are derived from a first species, and all of the constant regions of a chimeric antibody are derived from a second species.

[0017] A "humanized antibody" refers to an antibody in which at least one amino acid in the framework region of a non-human variable region is replaced with the corresponding amino acid from a human variable region. In some embodiments, a humanized antibody comprises at least one human constant region or fragment thereof. In some embodiments, a humanized antibody is a Fab, scFv, (Fab')2, etc.

[0018] "Human antibody," as used herein, refers to antibodies produced in humans, antibodies produced in non-human animals that contain human immunoglobulin genes, such as XenoMouse®, and antibodies selected using in vitro methods, such as phage display, whose antibody repertoire is based on human immunoglobulin sequences.

[0019] A "VISTA antibody" or "anti-VISTA antibody," as used herein, refers to an antibody that specifically binds to VISTA under at least some conditions, such as acidic pH. In some embodiments, the antibody may be a "huVISTA antibody" or "anti-huVISTA antibody," which exhibits specific binding to human VISTA protein under at least some conditions, such as acidic pH. A VISTA antibody that specifically binds to the extracellular domain (ECD) of VISTA may be referred to, for example, as a "VISTA-ECD antibody."

[0020] In some embodiments, the antibody may bind to VISTA with higher affinity at acidic pH than at neutral and / or physiological pH, hi some embodiments, the antibody may bind to VISTA with higher affinity at acidic pH and may bind negligibly or non-specifically at neutral and / or physiological pH.

[0021] The "K" of antibody binding to a protein, e.g., the VISTA-ECD protein D " or "dissociation constant" is a measure of the affinity or specific binding of an antibody to a protein, e.g., a VISTA-ECD protein. D is higher K Dexhibits improved binding or affinity over K D is the "dissociation rate" or k for antibodies and polypeptides. off or k d and the "association rate" or k on or k a The dissociation rate and association rate are the rates at which two binding partners associate and dissociate in a system. Thus, if the dissociation rate is slower and the association rate remains roughly constant, there is a higher overall affinity, and therefore a lower K D As used herein, a k off is k off or the "dissociation rate" is as specified or slower than the specified rate.

[0022] The term "specific binding" or "specifically binds" or similar terms refers to the K of binding of two polypeptides, such as an antibody and its polypeptide target. D is lower than that between two random polypeptides present under the same conditions. D is lower than that due to non-specific aggregation of polypeptides in the system.

[0023] In some embodiments, an antibody specifically binds to a VISTA-ECD protein at a particular pH or pH range. An "acidic" pH, as used herein, generally refers to a pH below 7.0, a "basic" pH generally refers to a pH above 7.0, and a "neutral" pH generally refers to a pH of about 7.0. A "physiological pH," as used herein, refers to a pH under normal (i.e., non-cancerous) physiological conditions, e.g., from 7.35 to 7.45, or from 7.3 to 7.4, such as about 7.4. As used herein, phrases such as "binding under acidic conditions" or "binding under physiological conditions," when used in the context of binding between two molecules, such as VISTA and a VISTA binding partner or VISTA and a T cell, refer to binding at acidic pH and binding at physiological pH, respectively.

[0024] When referring to an antibody that "blocks binding" or "inhibits binding" of a ligand (or receptor), or a competing antibody to the receptor (or ligand) alone or to cells, binding is blocked if there is a statistically significant overall reduction compared to the control, e.g., a 50% or greater overall reduction, e.g., a 75%, 80%, 85%, 90%, 95% or greater overall reduction. An "anti-VISTA blocking antibody" is one that can block binding of VISTA to PSGL-1 or another VISTA ligand or receptor or heparan sulfate proteoglycans under at least some conditions, e.g., acidic pH.

[0025] "Tumor model," as used herein, refers to an in vivo preclinical assay that can be used to study the biological activity of a VISTA-ECD antibody, and includes xenograft or native mouse tumor assay systems. In some cases, the tumor model may make it possible to track tumor size or growth upon treatment with the antibody and / or to track the presence of immune cells in the tumor, such as specific types of T cells or NK cells, to determine whether the antibody has initiated or enhanced an immune response.

[0026] The term "immunostimulatory agent," as used herein, refers to a molecule that stimulates the immune system by either acting as an agonist of immunostimulatory molecules, including costimulatory molecules, or as an antagonist of immunoinhibitory molecules, including coinhibitory molecules. The immunostimulatory or immunoinhibitory molecule may be an immune checkpoint regulator, such as VISTA or another B7 family member, or another molecule as further described below. The immunostimulatory agent may be a biologic, such as an antibody or antibody fragment, other protein, or vaccine, or may be a small molecule drug. "Immunostimulatory molecules" include receptors or ligands that act to enhance, stimulate, induce, or otherwise "turn on" an immune response. As defined herein, immunostimulatory molecules include costimulatory molecules. "Immunoinhibitory molecules" include receptors or ligands that act to reduce, inhibit, suppress, or otherwise "turn off" an immune response. As defined herein, immunoinhibitory molecules include coinhibitory molecules. Such immunostimulatory and immunoinhibitory molecules may be, for example, receptors or ligands found on immune cells such as T cells or on cells involved in innate immunity such as NK cells.

[0027] "Percent (%) amino acid sequence identity" and "homology" with respect to a peptide, polypeptide, or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in a particular peptide or polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity; any conservative substitutions are not considered part of the sequence identity. Alignment to determine percent amino acid sequence identity can be achieved in a variety of ways within the skill of the art, using publicly available computer software, such as, for example, BLAST, BLAST-2, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment across the full length of the sequences being compared.

[0028] The terms "prime" or "enhance" refer to the initiation or increase of any event (such as protein-ligand binding), or the initiation or increase of any biological activity (such as an immune response) or phenotypic characteristic, or an increase in the initiation or occurrence, degree, or likelihood of that activity or characteristic. "prime" or "enhance" refers to the initiation or increase of an activity, function, and / or amount compared to a reference. Initiation or enhancement need not be complete. For example, in certain embodiments, "enhance" refers to the ability to cause a 20% or greater overall increase. In another embodiment, "enhance" refers to the ability to cause a 50% or greater overall increase. In yet other embodiments, "enhance" refers to the ability to cause a 75%, 85%, 90%, 95%, or greater overall increase.

[0029] The term "inhibition" or "inhibiting" more generally refers to the reduction or interruption of any event (such as protein-ligand binding), or the reduction or interruption of any phenotypic characteristic, or the reduction or interruption of the occurrence, degree, or likelihood of that characteristic. "Reducing" or "inhibiting" is the decrease, reduction, or cessation of an activity, function, and / or amount compared to a reference standard. Inhibition or reduction need not be complete. For example, in certain embodiments, "reducing" or "inhibiting" refers to the ability to cause a 20% or greater overall reduction. In another embodiment, "reducing" or "inhibiting" refers to the ability to cause a 50% or greater overall reduction. In yet other embodiments, "reducing" or "inhibiting" refers to the ability to cause a 75%, 85%, 90%, 95%, or greater overall reduction.

[0030] "Treatment," as used herein, encompasses any administration or application of a therapeutic agent for a disease in a human, including inhibiting the disease, or the progression of the disease, or one or more symptoms thereof, inhibiting or slowing the disease, or its progression, or one or more symptoms thereof, arresting its onset, partially or completely alleviating the disease or one or more symptoms thereof, or preventing the recurrence of one or more symptoms of the disease.

[0031] The terms "subject" and "patient" are used interchangeably herein and refer to a human.

[0032] The term "effective amount" or "therapeutically effective amount" refers to an amount of a drug effective in treating a disease or disorder of interest, e.g., to partially or completely alleviate one or more symptoms. In some embodiments, an effective amount refers to an amount effective, at dosages and for periods of time, to achieve a desired therapeutic or prophylactic result.

[0033] The term "cancer" is used herein to refer to a group of cells that exhibit abnormally high levels of proliferation and growth. Cancers can be benign (also called benign tumors), pre-malignant, or malignant. Cancer cells can be solid cancer cells or leukemic cancer cells. The term "tumor growth" is used herein to refer to proliferation or growth by a cell(s) comprising the cancer, leading to a corresponding increase in the size or extent of the cancer.

[0034] Examples of cancers amenable to the treatment methods herein include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More specific, non-limiting examples of such cancers include squamous cell carcinoma, small cell lung cancer, pituitary cancer, esophageal cancer, astrocytoma, soft tissue sarcoma, non-small cell lung cancer (including squamous cell non-small cell lung cancer), adenocarcinoma of the lung, squamous cell carcinoma of the lung, cancer of the peritoneum, hepatocellular carcinoma, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, liver cancer, breast cancer, colon cancer, colorectal cancer, endometrial or uterine cancer, salivary gland cancer, kidney cancer, renal cell carcinoma, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, hepatocellular carcinoma, brain cancer, endometrial cancer, testicular cancer, bile duct cancer, gallbladder cancer, gastric cancer, melanoma, and various types of head and neck cancer (including squamous cell carcinoma of the head and neck).

[0035] Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) and consecutive (sequential) administration in any order.

[0036] A "pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid, or liquid filler, diluent, encapsulating material, formulation aid, or carrier conventional in the art for use in therapeutic agents that together comprise a "pharmaceutical composition" for administration to a subject. A pharmaceutically acceptable carrier is non-toxic to recipients at the dosages and concentrations used and is compatible with the other ingredients of the formulation. A pharmaceutically acceptable carrier is appropriate for the formulation used. For example, if the therapeutic agent is administered orally, the carrier may be a gel capsule. If the therapeutic agent is administered subcutaneously, the carrier ideally is not irritating to the skin and does not cause injection site reactions.

[0037] A "chemotherapeutic agent" is a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents that can be administered in accordance with the methods herein include, but are not limited to, alkylating agents such as thiotepa and Cytoxan® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan, and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines, including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide, and trimethylolomelamine; acetogenins (particularly bullatacin and bullatacinone); camptothecin (including the synthetic analog topotecan); brinzimidazole; Ostatin; kallistatin; CC-1065 (including its synthetic analogs adozelesin, carzelesin, and biceresin); cryptophycins (especially cryptophycin 1 and cryptophycin 8); dolastatins; duocarmycins (including synthetic analogs kW-2189 and CB1-TM1); eluterobin; pancratistatin; sarcodictyin; spongistatin; chlorambucil, chlornaphazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine nitrogen mustards, such as thiamine oxide hydrochloride, melphalan, nobuenbiquine, fenesterine, prednimustine, trofosfamide, and uracil mustard; nitrosureas, such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; enediyne antibiotics, such as calicheamicin, particularly calicheamicin gamma 11 and calicheamicin omega 11 (see, e.g., Agnew, Chem Intl. Ed. Engl., 33:183-186 (1994));Dynemicins, including dynemicin A; bisphosphonates such as clodronate; esperamicin; and neocarzinostatin chromophore and related chromoprotein (enediyne antibiotic chromophores), aclacinomycins, actinomycin, autramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycinis ), dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, Adriamycin® doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin, and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins , peplomycin, potfiromycin, puromycin, queramycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetrexate; fludarabine, 6-mercaptopropanol Purine analogs such as thiamiprine, thiamiprine, and thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and floxuridine; androgens such as calciterone, dromostanolone propionate, epithiostanol, mepitiostane, and testolactone; antiadrenal agents such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as furoic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestravcil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine;Elliptinium acetate; epothilone; etoglucide; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocin; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oregon; razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2''-trichlorotriethylamine; trichothecenes (particularly T-2 toxin, veracrine A, roridin A, and anguidine); urethane; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids, such as Taxol® paclitaxel (Bristol-Myers Squibb Oncology, Princeton, New Jersey), Abraxane® Cremophor Free, an albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, Illinois), and Taxotere® doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; Gemzar® gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin, and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; Navelbine® vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; Xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including treatment regimens of irinotecan with 5-FU and leucovorin);topoisomerase inhibitors RFS 2000; difluorometlhylornithine (DMFO); retinoids such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin, including the oxaliplatin treatment regimen (FOLFOX); inhibitors of PKC-alpha, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva®)), and VEGF-A, which reduce cell proliferation, and pharmaceutically acceptable salts, acids, or derivatives of any of the above;

[0038] Additional non-limiting exemplary chemotherapeutic agents that can be administered in the methods herein include: antihormonal agents that act to regulate or inhibit hormone action on cancer, such as antiestrogens and selective estrogen receptor modulators (SERMs), including, for example, tamoxifen (including Nolvadex® tamoxifen), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and Fareston® toremifene; enzymes that regulate estrogen production in the adrenal glands, such as, for example, 4(5)-imidazoles, aminoglutethimide, Megase® megestrol acetate, Aromasin® exemestane, formestani, fadrozole, Rivisor® vorozole, Femara® letrozole, and Arimidex® anastrozole. and antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; and troxacitabine (a 1,3-dioxolane nucleoside cytosine analog); antisense oligonucleotides, particularly those that inhibit the expression of genes in signaling pathways involved in abherent cell growth, such as PKC-alpha, Ralf, and H-Ras; ribozymes such as VEGF expression inhibitors (e.g., Angiozyme® ribozyme) and HER2 expression inhibitors; gene therapy vaccines such as Allovectin® vaccine, Leuvectin® vaccine, and Vaxid® vaccine; Proleukin® rIL-2; Lurtotecan® topoisomerase 1 inhibitor; Abarelix® rmRH; and pharmaceutically acceptable salts, acids, or derivatives of any of the above.

[0039] "Anti-angiogenic agent" or "angiogenesis inhibitor" refers to a low molecular weight substance, polynucleotide (including, for example, inhibitory RNA (RNAi or siRNA)), polypeptide, isolated protein, recombinant protein, antibody, or conjugate or fusion protein thereof that inhibits angiogenesis, vasculogenesis, or undesired vascular permeability either directly or indirectly. It should be understood that anti-angiogenic agents include agents that bind to angiogenic factors or their receptors and block their angiogenic activity. For example, anti-angiogenic agents that can be administered in the methods herein include antibodies or other antagonists to angiogenic agents, such as antibodies to VEGF-A (e.g., bevacizumab (Avastin®) or antibodies to a VEGF-A receptor (e.g., KDR receptor or Flt-1 receptor), anti-PDGFR inhibitors such as Gleevec® (imatinib mesylate), small molecules that block VEGF receptor signaling (e.g., PTK787 / ZK2284, SU6668, Sutent® / SU11248 (sunitinib malate), AMG706, or those described, for example, in WO 2004 / 113304). Anti-angiogenic agents also include natural angiogenesis inhibitors, such as angiostatin, endostatin, etc. See, e.g., Klagsbrun and D'Amore (1991) Annu. Rev. See Physiol. 53:217-39; Streit and Detmar (2003) Oncogene 22:3172-3179 (e.g., Table 3, listing antiangiogenic treatments for malignant melanoma); Ferrara & Alitalo (1999) Nature Medicine 5(12):1359-1364; Tonini et al. (2003) Oncogene 22:6549-6556 (e.g., Table 2, listing known antiangiogenic factors); Sato (2003) Int. J. Clin. Oncol. 8:200-206 (e.g., Table 1, listing antiangiogenic agents used in clinical trials).

[0040] As used herein, a "growth inhibitor" refers to a compound or composition that inhibits the proliferation of cells (such as cells expressing VEGF) either in vitro or in vivo. Thus, a growth inhibitor that can be administered in the methods herein may significantly reduce the percentage of cells in S phase (such as cells expressing VEGF). Examples of growth inhibitors include, but are not limited to, agents that block cell cycle progression (at a point other than S phase), such as agents that induce G1 arrest and M-phase arrest. Classical M-phase blockers include vincas (vincristine and vinblastine), taxanes, and topoisomerase II inhibitors such as doxorubicin, epirubicin, daunorubicin, etoposide, and bleomycin. Additionally, agents that arrest G1 spill over into S-phase arrest. For example, DNA alkylating agents such as tamoxifen, prednisone, dacarbazine, mechlorethamine, cisplatin, methotrexate, 5-fluorouracil, and ara-C. Further information can be found in Mendelsohn and Israel (eds.), The Molecular Basis of Cancer, Chapter 1, entitled "Cell cycle regulation, oncogenes, and antineoplastic drugs," by Murakami et al. (WB Saunders, Philadelphia, 1995), e.g., page 13. The taxanes (paclitaxel and docetaxel) are anticancer drugs both derived from the yew tree. Docetaxel (Taxotere®, Rhone-Poulenc Rorer), derived from the European yew, is a semisynthetic analog of paclitaxel (Taxol®, Bristol-Myers Squibb). Paclitaxel and docetaxel promote the assembly of microtubules from tubulin dimers and stabilize microtubules by preventing depolymerization, which leads to the inhibition of mitosis in cells.

[0041] The term "anti-tumor composition" refers to a composition useful for treating cancer, comprising at least one active therapeutic agent. Examples of therapeutic agents include, but are not limited to, chemotherapeutic agents, growth inhibitors, cytotoxic agents, agents used in radiation therapy, anti-angiogenic agents, cancer immunotherapeutic agents, apoptotic agents, anti-tubulin agents, and other agents for treating cancer, such as anti-HER-2 antibodies, anti-CD20 antibodies, epidermal growth factor receptor (EGFR) antagonists (e.g., tyrosine kinase inhibitors), HER1 / EGFR inhibitors (e.g., erlotinib (Tarceva®)), platelet-derived growth factor inhibitors (e.g., Gleevec® (imatinib mesylate)), COX-2 inhibitors (e.g., celecoxib), interferons, CTLA4 inhibitors ( For example, the anti-CTLA antibody ipilimumab (YERVOY®), PD-1 or PD-L1 inhibitors (e.g., OPDIVO®, KEYTRUDA®, TECENTRIQ®, BAVENCIO®, IMFINZI®), TIM3 inhibitors (e.g., anti-TIM3 antibodies), cytokines, antagonists (e.g., neutralizing antibodies) that bind to one or more of the following targets: ErbB2, ErbB3, ErbB4, PDGFR-beta, BlyS, APRIL, BCMA, CTLA4, TIM3, or VEGF receptors, TRAIL / Apo2, and other bioactive and organic chemical agents. Combinations of these are also included in the present disclosure.

[0042] Antibody that specifically binds to VISTA-ECD at acidic pH VISTA has a large number of histidine residues in its ECD, which alters its folding and overall structure, as well as the surface available for binding of ligands such as antibodies, at acidic pH compared to neutral pH, particularly the pK of histidine. a This may be different from the pH around 6.5, which is generally acidic in tumor microenvironments, and in order for an antibody to bind to VISTA in such a microenvironment, it may be necessary for the antibody to specifically bind to VISTA at an acidic pH, where at least some of the surface histidine residues are more likely to be protonated.

[0043] The sequence listing below provides the amino acid sequences of human VISTA (hVISTA) with and without the signal peptide (SEQ ID NO: 1 and SEQ ID NO: 2 (mature hVISTA) respectively. The signal peptide consists of amino acid residues 1-32 of SEQ ID NO: 1. The extracellular domain (ECD) consists of amino acid residues 1-162 of SEQ ID NO: 2). The IgV domain consists of amino acid residues 37-167 of SEQ ID NO: 1 and amino acid residues 5-135 of SEQ ID NO: 2. The stalk region consists of amino acid residues 172-194 of SEQ ID NO: 1 and amino acid residues 136-162 of SEQ ID NO: 2. The transmembrane domain consists of amino acid residues 195-216 of SEQ ID NO: 1 and amino acid residues 163-184 of SEQ ID NO: 2. Amino acid residue 187 of SEQ ID NO: 1 and residue 155 of SEQ ID NO: 2 (bold and underlined) may be either D or E and represent polymorphisms of hVISTA. The residues are shown in bold and underlined. Thus, SEQ ID NO: 1 and SEQ ID NO: 2 encompass both human polymorphisms at that residue. The histidine residues in the ECD of VISTA are shaded in grey.

[0044] An anti-VISTA antibody (Ab) can specifically bind to VISTA-ECD or a fragment thereof at an acidic pH, for example, comprising the IgV domain of VISTA or a region derived from hVISTA, for example, comprising amino acids 20-95, 20-70, 35-70, 35-95, 35-127, or 37-125 of SEQ ID NO: 2. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 7.0. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 6.8. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 6.5. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 6.3. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 6.0. In certain embodiments, an Ab specifically binds to VISTA-ECD protein at a pH below 5.8. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH below pH 5.5. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH below pH 5.3. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH below pH 5.0.

[0045] Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 5.0 to pH 7.0. Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 5.0 to pH 6.5. Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 5.0 to pH 6.0. Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 5.5 to pH 7.0. Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 5.5 to pH 6.5. Certain Abs specifically bind to VISTA-ECD protein at a pH within the range of pH 6.0 to pH 6.5.

[0046] Also provided herein are methods for treating a VISTA-ECD protein, such as hVISTA-ECD or a fragment thereof, comprising the IgV domain of VISTA, or a region derived from hVISTA, for example, comprising amino acids 20-95, 20-70, 35-70, 35-95, 35-127, or 37-125 of SEQ ID NO: 2, at a pH of 6.5 or lower, for 10 minutes. -6 M or a smaller K D In some embodiments, the Ab binds at 10 -7 M or a smaller K D In some embodiments, the Ab binds at 10 -8 M or a smaller K D In some embodiments, the Ab binds at 10 -9 K of M D In some embodiments, the Ab binds at 10 -10 M or a smaller K D For example, Abs bind at 10 at pH 6.5 or lower. -8 M or a smaller K D can bind to the VISTA-ECD protein.

[0047] In this specification, the pH range is 6.0 to 6.5. -6 M or a smaller K D In some embodiments, the Ab binds to the VISTA-ECD protein at 10 -7 M or a smaller K D In some embodiments, the Ab binds at 10 -8 M or a smaller K D In some embodiments, the Ab binds at 10 -9 K of M D In some embodiments, the Ab binds at 10 -10 M or a smaller K D For example, Abs bind at pH 6.5 or lower, e.g., in the pH range of 6.0 to 6.5, at 10 -7 M or a smaller K DFurthermore, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, for example, within the pH range of 6.0 to 6.5, with a 10 -8 M or a smaller K D The Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, for example, in the pH range of 6.0 to 6.5, at a pH of 10 -9 M or a smaller K D can bind to hVISTA-ECD.

[0048] Also provided herein are methods for treating a VISTA-ECD protein, such as hVISTA-ECD or a fragment thereof, comprising the IgV domain of VISTA or a region derived from hVISTA, e.g., comprising amino acids 20-95, 20-70, 35-70, 35-95, 35-127, or 37-125 of SEQ ID NO: 2, at either 25°C or 37°C, at a pH of 6.5 or lower, for 10 minutes. -5 s -1 or a smaller k off In some embodiments, the Ab binds at 10 at either 25° C. or 37° C. -4 s -1 or a smaller k off In some embodiments, the Ab has a 2 10 -4 s -1 or a smaller k off In some embodiments, the Ab has a 5 to 10 -4 s -1 or a smaller k off In some embodiments, the Ab has a 7 to 10 -4 s -1 or smaller koff In some embodiments, the Ab has a 10 -3 s -1 or a smaller k offIn some embodiments, the Ab has a 2 10 -3 s -1 or a smaller k off In some embodiments, the Ab has a 5 to 10 -3 s -1 or a smaller k off In some embodiments, the Ab has a 7 to 10 -3 s -1 or a smaller k off In some embodiments, the Ab has a 10 -2 s -1 k off In some embodiments, the Ab has a 10 -1 s -1 or a smaller k off For example, the Ab has a 10 -3 s -1 or a smaller k off The Ab can specifically bind to the VISTA-ECD protein at 10°C at either 25°C or 37°C, at a pH of 6.5 or lower. -3 s -1 or a smaller k off Furthermore, the Abs are capable of specifically binding to hVISTA-ECD at either 25°C or 37°C, at pH 6.5 or lower, and at 10 -2 s -1 or a smaller k off and can specifically bind to the VISTA-ECD protein.

[0049] As used herein, a VISTA-ECD protein, such as hVISTA-ECD or a fragment thereof, comprising the IgV domain of VISTA, or a region derived from hVISTA, e.g., comprising amino acids 20-95, 20-70, 35-70, or 35-95, 35-127, or 37-125 of SEQ ID NO: 2, is subjected to a 100-fold increase in saturation, e.g., at a pH of 6.5 or lower, e.g., measured at 25°C or 37°C, of ​​(i) 10 -6 M or smaller, 10 -7 M or smaller, 10 -8 M or smaller, 10 -9 M or smaller, or 10 -10 M or a smaller K D and (ii) 10 -5 s -1 Or smaller, 10 -4 (or 2, 5, or 7 10 -4 )s -1 Or smaller, 10 -3 (or 2, 5, or 7 10 -4 )s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off For example, Abs that bind at a rate of 10, as measured at pH 6.5 or lower, e.g., at 25°C or 37°C, are provided. -7 M or a smaller K D and 10 -3 s -1 or a smaller k off The Abs can bind to the VISTA-ECD protein at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -8 M or a smaller K D and 10 -3 s -1 or a smaller k offThe Abs can bind to the VISTA-ECD protein at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -8 M or a smaller K D and 10 -2 s -1 or a smaller k off For example, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., at 25°C or 37°C, with a binding rate of 10 -7 M or a smaller K D and 10 -3 s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -9 M or a smaller K D and 10 -3 s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -9 M or a smaller K D and 10 -2 s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -8 M or a smaller K D and 10 -4 (or 2, 5, or 7 10 -4 )s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -8 M or a smaller K D and 10 -5(or 2, 5, or 7 10 -5 )s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -9 M or a smaller K D and 10 -4 (or 2, 5, or 7 10 -4 )s -1 or a smaller k off The Ab can bind to hVISTA-ECD at a rate of 10, measured at pH 6.5 or lower, e.g., at 25°C or 37°C. -9 M or a smaller K D and 10 -5 (or 2, 5, or 7 10 -5 )s -1 or a smaller k off It can bind to hVISTA-ECD at high speed.

[0050] As used herein, 10 4 M -1 s -1 higher than k on In some such embodiments, the Ab specifically binds to the VISTA-ECD protein at a concentration of 10 5 M -1 s -1 or higher k on In some such embodiments, the Ab can bind at 10 6 M -1 s -1 or higher k on In some such embodiments, the Ab can bind at 10 7 M -1 s -1 or higher k on For example, Abs can bind at 10 s at a pH of 6.5 or lower, e.g., measured at 25°C or 37°C.6 M -1 s -1 or higher k on For example, the Ab can bind to the VISTA-ECD protein at a pH of 10 or less, measured at, for example, 25° C. or 37° C., at a pH of 6.5 or less. 6 M -1 s -1 or higher k on and can bind to the ECD of hVISTA.

[0051] As used herein, a VISTA-ECD protein is provided that exhibits (i) a 10 -6 M or smaller, 10 -7 M or smaller, 10 -8 M or smaller, 10 -9 M or smaller, or 10 -10 M or a smaller K D and (ii) 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on For example, the Abs may bind at a pH of 6.5 or lower, e.g., at 25°C or 37°C, with a binding affinity of 10 -7 M or a smaller K D and 10 6 M -1 s -1 or higher k on For example, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., at 25°C or 37°C, with a binding rate of 10 -8M or a smaller K D and 10 6 M -1 s -1 or higher k on For example, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., at 25°C or 37°C, with a binding rate of 10 -7 M or a smaller K D and 10 6 M -1 s -1 or higher k on For example, the Ab can bind to hVISTA-ECD at a pH of 6.5 or lower, e.g., at 25°C or 37°C, at a rate of 10 -8 M or a smaller K D and 10 6 M -1 s -1 or higher k on It can bind to hVISTA-ECD at high speed.

[0052] In some embodiments, the Ab has a 10% or higher activity at a pH of 6.5 or lower, e.g., measured at 25°C or 37°C. -7 M or a smaller K D And 10 -5 s -1 or smaller, 2 10 -5 s -1 or smaller, 5 10 -5 s -1 or smaller, 7 10 -5 s -1 Or smaller, 10 -4 s -1 or smaller, 2 10 -4 s -1 or smaller, 5 10 -4 s -1 or smaller, 7 10 -4 s -1 Or smaller, 10 -3 s-1 or smaller, 2 10 -3 s -1 or smaller, 5 10 -3 s -1 or smaller, 7 10 -3 s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off In some embodiments, the Abs are capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., as measured at 25°C or 37°C, at a binding affinity of 10 -9 M or a smaller K D And 10 -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off In some such embodiments, the Abs are capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., as measured at 25°C or 37°C, at a binding affinity of 10 -10 M or a smaller K D And 10 -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s-1 or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off and can bind to the VISTA-ECD protein.

[0053] In some embodiments, the Ab has a 10% or higher activity at a pH of 6.5 or lower, e.g., measured at 25°C or 37°C. -7 M or a smaller K D And 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on In some embodiments, the Abs are capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., as measured at 25°C or 37°C, at a binding affinity of 10 -8 M or a smaller K D And 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on In some embodiments, the Abs are capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., as measured at 25°C or 37°C, at a binding affinity of 10 -9 M or a smaller K D And 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 107 M -1 s -1 or higher k on In some such embodiments, the Abs are capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower, e.g., as measured at 25°C or 37°C, at a binding affinity of 10 -10 M or a smaller K D And 10 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on and can bind to the VISTA-ECD protein.

[0054] In some embodiments, the Ab is at a pH of 6.5 or lower and -7 M or a smaller K D and, for example, at 25°C or 37°C. -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off and, for example, at 25°C or 37°C, 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1or higher, 10 7 M -1 s -1 or higher k on In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower and at a pH of 10 -8 M or a smaller K D and, for example, at 25°C or 37°C. -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s -1 Or smaller, 10 -2 s-1 or smaller, or 10 -1 s -1 Or a smaller k off and, for example, at 25°C or 37°C, 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower and at a pH of 10 -9 M or a smaller K D and, for example, at 25°C or 37°C. -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1Or a smaller k off and, for example, at 25°C or 37°C, 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on In some such embodiments, the Ab is capable of binding to the VISTA-ECD protein at a pH of 6.5 or lower and at a pH of 10 -10 M or a smaller K D and, for example, at 25°C or 37°C. -5 s -1 Or smaller, 10 -4 s -1 Or smaller, 10 -3 s -1 Or smaller, 10 -2 s -1 or smaller, or 10 -1 s -1 Or a smaller k off and, for example, at 25°C or 37°C, 4 M -1 s -1 or higher, 10 5 M -1 s -1 or higher, 10 6 M -1 s -1 or higher, 10 7 M -1 s -1 or higher k on and can bind to the VISTA-ECD protein.

[0055] As noted above, in some of the above embodiments, the VISTA-ECD protein is hVISTA-ECD or a portion of hVISTA-ECD, such as the IgV domain. In some of the above embodiments, the Ab is capable of specifically binding to an epitope comprising amino acids 20-95 of SEQ ID NO:2. In some of the above embodiments, the Ab is capable of specifically binding to an epitope comprising amino acids 20-70 of SEQ ID NO:2. In some of the above embodiments, the Ab is capable of specifically binding to an epitope comprising amino acids 35-95 of SEQ ID NO:2. In some of the above embodiments, the Ab is capable of specifically binding to an epitope comprising amino acids 35-70 of SEQ ID NO:2. In some of the above embodiments, the epitope is a three-dimensional epitope that includes not only one of the above portions of SEQ ID NO:2 derived from residues 20-95, 20-70, 35-95, or 35-70, but also another portion of SEQ ID NO:2, such as residues 95-105 of SEQ ID NO:2. In certain embodiments, the Ab binds to an epitope of hVISTA bound by the Abs disclosed in WO 2015 / 097536. For example, the Ab can compete or cross-compete for binding to hVISTA with the Abs disclosed in WO 2015 / 097536. In certain embodiments, the Ab binds to a conformational epitope of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising or residing within residues 103-111 of SEQ ID NO:2 and 136-146 of SEQ ID NO:2 of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising or residing within residues 24-36, 54-65, and 100-102 of SEQ ID NO:2 of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising amino acid residues of the FG loop of human VISTA. In some embodiments, the Ab binds to a polypeptide comprising amino acid residues 35-127 and / or 37-125 of SEQ ID NO:2.In some embodiments, the Ab binds to a VISTA ECD polypeptide or portion thereof comprising amino acid residues 350-127 of SEQ ID NO:2, but the antibody does not bind, or binds with reduced affinity, to a VISTA ECD polypeptide or portion thereof comprising an amino acid substitution (1) at one of the following amino acid residues: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127, and SEQ ID NO:2, or (2) at one of the following amino acid residues: Y37, T39, R54, F62, Q63, H66, L115, V117, I119, S124, or E125. In some embodiments, the anti-VISTA antibody has the same binding characteristics (or significantly the same binding characteristics) as the antibodies described herein, eg, in the Examples.

[0056] Some of the above antibodies may exhibit differences in binding affinity to the VISTA-ECD protein depending on pH. Certain Abs that specifically bind to the VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or lower, also specifically bind to the VISTA-ECD protein with similar affinity at neutral and / or alkaline pH (i.e., they are "pan-binders"). For example, some such Abs have a binding affinity of 10 at both pH 6.5 and pH 7.0 (at a constant temperature, e.g., 25°C or 37°C). -7 M or a smaller K D can bind to the VISTA-ECD protein at pH 6.5. D is the K at pH 7.0 D Some such Abs have a 10 fold increase in activity at both pH 6.5 and pH 7.0 (at a constant temperature, e.g., 25°C or 37°C). -8 M or a smaller K D can bind to the VISTA-ECD protein at pH 6.5. D is the K at pH 7.0 DSome such Abs have a 10 fold increase in activity at both pH 6.5 and pH 7.0 (at a constant temperature, e.g., 25°C or 37°C). -8 M or a smaller K D can bind to hVISTA-ECD at pH 6.5. D is the K at pH 7.0 D It is within 1.5 times of

[0057] Certain Abs that specifically bind to VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or lower, may bind to VISTA-ECD protein with lower affinity under neutral, physiological, and / or alkaline conditions ("pH-sensitive binders" or "pH-sensitive Abs"). Certain Abs that specifically bind to VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or lower, may exhibit insignificant, e.g., nearly undetectable, binding to VISTA-ECD protein under neutral, physiological, and / or alkaline conditions. For example, in some embodiments, the Abs exhibit a 10 -8 M or a smaller K D 10 at pH 7.0 and / or pH 7.4 -8 M or larger K D In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 10 -8 M or a smaller K D At pH 7.0 and / or pH 7.4, K at pH 6.5 D More than 1.5 times higher K D In certain embodiments, the K at pH 6.5 is at least 1.5, 2, 5, 10, 20, 50, 100, 300, 500, 1000, or 5000 times lower than at pH 7.0. DpH-sensitive Abs that specifically bind to VISTA-ECD protein at a constant temperature (e.g., 25° C. or 37° C.) are provided. For example, in some cases, the Ab may have a K that is 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 300-fold, 500-fold, 1000-fold, or 5000-fold or less at pH 6.0 compared to pH 7.0 and / or pH 7.4 or higher. D (for example, at a constant temperature of 25°C or 37°C) to bind to the VISTA-ECD protein.

[0058] In certain embodiments, Abs exhibit a kappa activity under acidic conditions compared to kappa activity under neutral, physiological, or alkaline conditions. off Lower k compared to off In certain embodiments, the VISTA-ECD protein specifically binds under acidic conditions, e.g., at pH 6.5, at pH 7.0, and / or at pH 7.4, as measured at 25°C or 37°C. off k less than 1 / 1.5, 1 / 2, 1 / 5, 1 / 10, 1 / 20, 1 / 50, 1 / 100, or 1 / 1000 of off Abs are provided that bind to VISTA-ECD proteins at a K of 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold or less at pH 6.0 compared to pH 7.0 and / or pH 7.4, e.g., measured at 25°C or 37°C. off In certain embodiments, the K at pH 6.5 is greater than or equal to the K at pH 7.4, e.g., as measured at 25°C or 37°C. off K less than 1 / 1.5, 1 / 2, 1 / 5, 1 / 10, 1 / 20, 1 / 50, 1 / 100, or 1 / 1000 of offIn some embodiments, the Abs have a K that is 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold lower at pH 6.0 compared to pH 7.4, e.g., measured at 25°C or 37°C. off In certain embodiments, the K specifically binds to the VISTA-ECD protein at a rate of 100 kJ / s, e.g., 100 kJ / s ... off K less than 1 / 1.5, 1 / 2, 1 / 5, 1 / 10, 1 / 20, 1 / 50, 1 / 100, or 1 / 1000 of off In this case, an Ab that binds to the VISTA-ECD protein is provided.

[0059] In certain embodiments, Abs have a higher k in acidic conditions compared to neutral, physiological, or alkaline conditions. on In certain embodiments, the K specifically binds to the VISTA-ECD protein under acidic conditions, e.g., at pH 6.5, pH 7.0, and / or 7.4, as measured at 25°C or 37°C. on at least 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold higher than on For example, in some embodiments, the Abs have a K that is at least 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold higher at pH 6.0 than at pH 7.0 and / or pH 7.4, e.g., measured at 25°C or 37°C. on and specifically binds to the VISTA-ECD protein.

[0060] In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH at which at least one histidine residue, e.g., His98 of SEQ ID NO: 1, is protonated. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH at or below pH 6.5, e.g., a pH at which most of the histidine residues in the ECD are protonated, which is expected to be between pH 6.0 and pH 6.5.

[0061] Also encompassed herein are Abs that specifically bind to VISTA-ECD protein with higher affinity at neutral, physiological, or alkaline pH compared to acidic pH, so long as the binding affinity remains high at acidic pH. For example, an Ab may have a K at pH 7.0 that is 1.5-, 2-, 5-, 10-, 20-, 50-, 100-, 300-, 500-, 1000-, or less than that at pH 6.5. D Even when binding at pH 6.5 and pH 7.0, the Ab binds at 10 -8 M or a smaller K D can bind to the VISTA-ECD protein.

[0062] Also encompassed herein are Abs that share one or more of the above characteristics in this section. D , k off , k on The above characteristics, such as specific epitopes, should not be treated in isolation. Thus, an Ab may bind to an epitope comprising one of the regions of SEQ ID NO:2 described above, and may also exhibit its K at different pHs, as described above. D , k off , k on The antibody may have general binding or pH-sensitive or pH-selective binding properties as demonstrated by one or more of the following behaviors:

[0063] In any of the above embodiments, the Ab may be, for example, a full-length antibody (i.e., comprising a full-length heavy chain (with or without a C-terminal lysine) and a full-length light chain), or may be an antigen-binding fragment such as a Fab fragment, a Fab' fragment, a (Fab')2 fragment, an scFv fragment, an Fv fragment, or the Ab may be a chimeric, humanized, or human antibody, or the Ab may be a bispecific or multispecific antibody.

[0064] Determining the binding affinity of an Ab to a VISTA-ECD protein at a given pH can be performed using several different methods, including surface plasmon resonance (SPR), such as a BIACORE® assay. An exemplary SPR assay involves capturing one or several antibodies on a CM4 sensor chip with immobilized capture reagents (e.g., using a Biacore® anti-human Fc capture kit, GE Healthcare catalog #BR-1008-39, or a Biacore® anti-mouse capture kit, GE Healthcare catalog #BR-1008-39), and running a concentration series of VISTA antigen as the analyte to determine binding kinetics and affinity in a running buffer at the desired pH. In one embodiment, VISTA is injected at two to five concentrations ranging from 0.1 nM to 500 nM (e.g., 0.1 nM, 1 nM, 10 nM, 100 nM, 500 nM) at a flow rate of 30 μL / min, with an association time of up to 4 minutes and a dissociation time of up to 10 minutes. Between binding cycles, the capture surface is regenerated according to the manufacturer's instructions for each capture kit. All data are double-referenced using a reference flow cell and a blank injection. Data from simple 1:1 kinetics are fitted to a Langmuir binding model of mass transfer using Biacore® T200 evaluation software. SPR methods, as described in the Examples, may also be used.

[0065] The affinity of Abs for VISTA ECD polypeptides can be determined using cells expressing VISTA ECD polypeptides, PSGL-1, or heparan sulfate on their surface. This method involves flow cytometry, in which the binding of Abs to cell-bound VISTA-ECD is determined at a given pH, e.g., pH 6.5 or lower. An exemplary flow cytometry assay involves resuspending 293T cells or other cells ectopically expressing hVISTA ECD in a buffer consisting of HBSS + 1% BSA adjusted to the desired pH, e.g., pH 6.0 with MES or pH 7.4 with HEPES. Serial dilutions of Abs against hVISTA (e.g., human IgG) starting at approximately 20 μg / mL are incubated with the resuspended cells at 4°C for 30 minutes. The cells are then washed twice with the same buffer, maintained at a desired pH, e.g., 6.0 or 7.4, and incubated with a fluorophore-conjugated secondary antibody that recognizes the primary antibody (e.g., human IgG) and is stable at low pH. The cells are then washed as above and immediately acquired on a BD Fortessa or other flow cytometer without fixation. The affinity of the Ab for the VISTA ECD polypeptide can be determined as described in the Examples.

[0066] In certain embodiments, an Ab that binds to hVISTA ECD blocks binding of hVISTA to its binding partner (e.g., a VISTA receptor), for example, on a cell. Inhibition or blocking may be 100%, or at least 99%, 95%, 90%, 85%, 80%, 75%, or 50%. In certain embodiments, an Ab binds to the VISTA-ECD protein at an acidic pH, e.g., pH 6.5 or lower, and inhibits binding of VISTA to its binding partner by at least 50%, such as at least 75%, 80%, 85%, 90%, 95%, or 100%. In certain embodiments, an Ab specifically binds to the VISTA-ECD protein at a pH below pH 7.0 and inhibits binding of VISTA to its binding partner by at least 50%. In certain embodiments, an Ab specifically binds to the VISTA-ECD protein at a pH below pH 6.8 and inhibits binding of VISTA to its binding partner by at least 50%. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below 6.5. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below 6.3. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below 6.0. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below 5.8. In certain embodiments, an Ab specifically binds to a VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below 5.5. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below pH 5.3.In certain embodiments, the Ab specifically binds to the VISTA-ECD protein and inhibits binding of VISTA to its binding partner by at least 50% at a pH below pH 5.0.

[0067] Certain Abs specifically bind to the VISTA-ECD protein and inhibit the binding of VISTA to its binding partner by at least 50% at a pH in the range of pH 5.0 to pH 7.0. Certain Abs specifically bind to the VISTA-ECD protein and inhibit the binding of VISTA to its binding partner by at least 50% at a pH in the range of pH 5.0 to pH 6.5. Certain Abs specifically bind to the VISTA-ECD protein and inhibit the binding of VISTA to its binding partner by at least 50% at a pH in the range of pH 5.0 to pH 6.0. Certain Abs specifically bind to the VISTA-ECD protein and inhibit the binding of VISTA to its binding partner by at least 50% at a pH in the range of pH 5.5 to pH 7.0. Certain Abs specifically bind to the VISTA-ECD protein and inhibit the binding of VISTA to its binding partner by at least 50% at a pH in the range of pH 5.5 to pH 6.5. Certain Abs specifically bind to the VISTA-ECD protein and inhibit binding of VISTA to its binding partner by at least 50% at pH values ​​between 6.0 and 6.5. Inhibition of binding can be determined as described in the Examples.

[0068] The VISTA binding partner may be PSGL-1, such as human PSGL-1. The sequences of human PSGL-1 isoforms are provided herein as SEQ ID NOS: 3-10. It may also be, for example, a heparan sulfate proteoglycan present on certain cells.

[0069] Inhibition of VISTA binding to a binding partner can be determined by measuring inhibition of binding of VISTA (or VISTA ECD, or VISTA IgV domain, or VISTA-positive cells) to cells to which VISTA binds, such as T cells (e.g., CD4+ T cells, CD8+ T cells, activated or not), NK cells, or other cells to which VISTA binds, in the presence or absence of the antibody. An exemplary experiment that can be used to determine whether an antibody inhibits VISTA binding to its binding partner, or to T cells expressing the binding partner, is a flow cytometry assay, for example, an assay comprising the following: Human peripheral blood mononuclear cells, buffy coat, or leukopak derived from donor blood are resuspended in a buffer composed of HBSS + 1% BSA adjusted to the desired pH, for example, pH 6.0 with MES or pH 7.4 with HEPES. The cells are then incubated with 20 μg / mL recombinant chimeric protein consisting of hVISTA ECD fused to human IgG1 Fc (VISTA-Fc) and various concentrations of candidate VISTA blocking or control antibodies for 30 minutes at 4°C. The cells are then washed twice with the same buffer to maintain a desired pH, e.g., 6.0 or 7.4, and incubated for an additional 30 minutes at 4°C with a fluorophore-conjugated secondary antibody that recognizes VISTA-Fc but not the candidate blocking or control antibody and is stable at low pH. The cells are then washed as above and immediately acquired on a BD Fortessa or other flow cytometer without fixation. Inhibition of binding can be determined, for example, as described in the Examples.

[0070] In specific embodiments, the Abs described herein can initiate or enhance an immune response, such as an antigen-specific immune response. In certain embodiments, the Abs stimulate T cell activity, particularly at acidic pH, such as that found in the tumor microenvironment. Stimulation of T cell activity can be measured, for example, in a mixed lymphocyte reaction (MLR) or in an in vitro assay using antigen-presenting cells (natural or artificial) and T cells. Stimulation of T cell activity can also be measured, for example, using the Jurkat assay described in the Examples.

[0071] In specific embodiments, the Abs described herein inhibit cell adhesion, which can be measured as described in the Examples.

[0072] Additionally, the activity of anti-VISTA Abs can be demonstrated in monocyte, ADCC, and ADCP assays, particularly at acidic pH such as found in the tumor microenvironment.

[0073] In certain embodiments, the anti-VISTA Abs inhibit tumor growth in a tumor model, for example, a human VISTA knock-in tumor model.

[0074] As shown in the Examples herein, the pharmacokinetic (PK) properties of the antibody, i.e., recycling of anti-VISTA Abs in endosomes to enhance half-life, etc., require that the anti-VISTA antibody bind to VISTA under acidic conditions. Thus, as further described herein, anti-VISTA Abs that bind to VISTA at low pH, e.g., at or below 6.5, are also expected to have a longer, acceptable half-life compared to VISTA antibodies that do not bind to VISTA at acidic pH.

[0075] Exemplary hVISTA-ECD Binding Abs Provided herein are Abs that bind preferentially to hVISTA (ECD) at acidic pH (eg, acidic conditions) relative to physiological or neutral pH.

[0076] In certain embodiments, an anti-hVISTA Ab comprises a heavy chain variable region ("VH") comprising the VH CDR1, CDR2, and / or CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH comprising the VH CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH of P1-061029 or P1-061015 or their progeny, such as VHs comprising CDR1, CDR2, and / or CDR3: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063 , P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-0 68736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF. The VH CDR1, CDR2, and CDR3 of each of these species comprise amino acids 26-35 (VH CDR1), 50-66 (VH CDR2), and 99-110 (VH CDR3) of the VH sequences of each of the above antibody species provided in the Sequence Listing below, and the CDRs of each of the VH sequences of the above antibody species provided in the Sequence Listing below are underlined and in bold.

[0077] In certain embodiments, an anti-hVISTA Ab comprises a VH that includes the VH CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH that includes the VH CDR1, CDR2, and CDR3 of one of the following: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P 1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-06 8736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF. The VL CDR1, CDR2, and CDR3 of each of these species comprise amino acids 24-35 (VL CDR1), 51-57 (VL CDR2), and 90-98 (VL CDR3) of the VL sequences of each of the above antibody species provided in the Sequence Listing below, with the CDRs of such sequences underlined and in bold.

[0078] In certain embodiments, an anti-hVISTA Ab comprises a VH that comprises the VH CDR1, CDR2, and / or CDR3 of any of the anti-hVISTA Abs provided herein, and a VL that comprises the CDR1, CDR2, and / or CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH that comprises the VH CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein, and a VL that comprises the CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH that comprises the VH CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein. Ab is P1-061029, or P1-061015, or P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063 , P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-0 68736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E 30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1 -068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-06 8761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E 32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-0 68767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, VHs of their progeny, such as P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fFa VH comprising CDR1, CDR2, and / or CDR3, and P1-061029, or P1-061015, or P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-06 9061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-0610 15, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E 30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1 -068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-06 8761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E 32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-0 68767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, and VLs comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or progeny thereof, such as P1-068767_E30D_E100fF.

[0079] In some embodiments, the anti-hVISTA Ab (a) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-061029, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-061029; (b) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-061015, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-061015; (c) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068757, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068757; (d) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068759, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068759; (e) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761; (f) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068763, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068763; (g) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068765, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068765; (h) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767; (i) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068769, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068769; (j) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068771, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068771; (k) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068773, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068773; (l) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068775, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068775; (m) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069059, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069059; (n) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069061, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069061; (o) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069063, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069063; (p) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069065, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069065; (q) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069067, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069067; (r) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069069, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069069; (s) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069071, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069071; (t) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069073, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069073; (u) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069075, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069075; (v) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069077, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-069077; (w) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068736, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068736; (x) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068738, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068738; (y) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068740, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068740; (z) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068742, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068742; (aa) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068744, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068744; (bb) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068746, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068746; (cc) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068748, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068748; (dd) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068750, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068750; (ee) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068752, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068752; (ff) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068754, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068754; (gg) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E55A, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E55A; (hh) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_H100G, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_H100G; (ii) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E56N; (jj) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E55A_E56N, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E55A_E56N; (kk) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D; (ll) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E55A, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E55A; (mm) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G; (nn) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G; (oo) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N; (pp) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E100fF; (qq) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF; (rr) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF; (ss) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF; (tt) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF; (uu) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E32Y; (vv) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E55A, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E55A; (ww) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E56N, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E56N; (xx) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E32Y, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E32Y; (yy) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_H100G, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_H100G; (zz) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E100fF, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E100fF; (aaa) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_D102V, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_D52N_D102V; (bbb) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D52N, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_D52N; (ccc) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_E55A, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_D52N_E55A; (ddd) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E55A_D102V, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E55A_D102V; (eee) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D102V, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_D102V; (fff) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E55A, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E55A; (ggg) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_D52N, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E30D_D52N; (hhh) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_D102V, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E30D_D102V; (iii) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E30D; (jjj) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_E55A, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E30D_E55A; (kkk) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V; (lll) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF, and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF; (mmm) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF; (nnn) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E100fF; (ooo) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_E100fF, and VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E30D_E100fF. may also include:

[0080] Again, the sequence listing below provides the heavy and light chain variable region sequences and full-length heavy and light chain sequences of the above-listed antibodies having an IgG1.3 heavy chain constant region (unless a different H constant region is noted in the table), with the positions of their VH CDR1, CDR2, and CDR3, and VL CDR1, CDR2, and CDR3 indicated by amino acid residues, with the CDRs of each VH and VL sequence indicated in bold and underlined. Thus, for example, as indicated by the bold and underlined amino acids of SEQ ID NO:67 shown in the sequence listing, VH CDR1 of P1-061029 comprises amino acids 26-35 of SEQ ID NO:67, VH CDR2 comprises amino acids 50-66 of SEQ ID NO:67, VH CDR3 comprises amino acids 99-110 of SEQ ID NO:67, etc.

[0081] In certain embodiments, an anti-hVISTA Ab comprises a VH that comprises the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein. Individual VH sequences of the particular antibody species provided herein are listed in the Sequence Listing. In certain embodiments, an anti-hVISTA Ab comprises a VH that comprises the amino acid sequence of the VH of P1-061029 or P1-061015 or a progeny thereof, such as: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069069, P1-069070, P1-069080, P1-069090, P1-0691029, P1-069115, P1-069125, P1-069135, P1-069145, P1-069155, P1-069165, P1-069170, P1-069185, P1-069190, P1-069191, P1-069192, P1-069193, P1-069194, P1-069195, P1-069196, P1-069197, P1-069198, P1-069199, P1-069109 69061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061 015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF. In certain embodiments, an anti-hVISTA Ab comprises a VH CDR1, CDR2, and CDR3 that comprise the amino acid sequences of the VH CDRs of any of the anti-hVISTA Abs provided herein, and that is 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% identical to the VH of any of the anti-hVISTA Abs provided herein.Ab is P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1 -069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_ E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55 A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_ E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767 _D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1 -068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-06 In certain embodiments, the anti-hVISTA Ab comprises a VH comprising an amino acid sequence that is 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% identical to the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises a VH consisting of the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein.The Ab comprises a VH consisting of the amino acid sequence of the VH of P1-061029 or P1-061015 or a progeny thereof, such as: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1- 069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061 015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF.

[0082] In certain embodiments, an anti-hVISTA Ab comprises a VL comprising the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VL comprising the amino acid sequence of the VL of P1-061029 or P1-061015 or a progeny thereof, such as: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069069, P1-069070, P1-069080, P1-069091, P1-069092, P1-069093, P1-069094, P1-069095, P1-069096, P1-069097, P1-069098, P1-069099, P1-069099, P1-069099, P1-069091, P1-069095, P1-069096, P1-069097, P1-069098, P1-069099, P1-069099, P1-069099, P1-069099, P1-069090, P1-069091, P1-069092, P1-069093, P1-069094, P1-069095, P1-069096 69061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061 015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF. In certain embodiments, an anti-hVISTA Ab comprises a VL CDR1, CDR2, and CDR3 that comprise the amino acid sequences of the VL CDRs of any of the anti-hVISTA Abs provided herein, and that is 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% identical to the VL of any of the anti-hVISTA Abs provided herein.Ab is P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1 -069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_ E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55 A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_ E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767 _D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1 -068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-06 In certain embodiments, the anti-hVISTA Ab comprises a VL comprising an amino acid sequence that is 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% identical to the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein.The Ab comprises a VL consisting of the amino acid sequence of the VL of P1-061029 or P1-061015 or a progeny thereof, such as: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1- 069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061 015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF.

[0083] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising the amino acid sequence of the VH of any of the anti-hVISTA Abs provided herein, and a VL comprising the amino acid sequence of the VL of any of the anti-hVISTA Abs provided herein. In certain such embodiments, the anti-hVISTA Ab is selected from the group consisting of P1-061029 or P1-061015 or P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-0 68736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1- 068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF , P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-0 68761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, P1- 068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E55A_D102 V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068 767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or a progeny thereof, such as P1-068767_E30D_E100fF, and a VL comprising the amino acid sequence of the VL of P1-061029 or P1-061015.Ab is P1-061029 or P1-061015 or P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-0 68736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D , P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-06876 1_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_ E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761 _E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P 1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V , P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF, or progeny thereof.

[0084] In certain embodiments, an anti-hVISTA Ab comprises a VH CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VH CDR of any of the anti-hVISTA Abs provided herein, and a VL CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VL CDR of any of the anti-hVISTA Abs provided herein, and comprises a VH and VL that are 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% identical, respectively, to the corresponding VH and VL of any of the anti-hVISTA Abs provided herein. containing all six CDRs of Ab, and also P1-061029 or P1-061015 or P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1- 069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P 1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30 D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068 761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E 56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-0 68761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N _E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E3 and VL of an anti-hVISTA Ab, such as P1-068767_E52N_E100fF, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or a progeny thereof, such as P1-068767_E30D_E100fF. In certain embodiments, the anti-hVISTA Ab comprises a VH and a VL consisting of the amino acid sequences of the VH and VL of any of the anti-hVISTA Abs provided herein.The Abs each comprise a VH and a VL consisting of the amino acid sequence of the VH and VL of P1-061029 or P1-061015 or a progeny thereof, such as: P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-0 69067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P 1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E3 0D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF.

[0085] Anti-hVISTA Ab (a) VH comprising the amino acid sequence of VH of P1-061029, and VL comprising the amino acid sequence of VL of P1-061029; (b) VH comprising the amino acid sequence of VH of P1-061015, and VL comprising the amino acid sequence of VL of P1-061015; (c) VH comprising the amino acid sequence of VH of P1-068757, and VL comprising the amino acid sequence of VL of P1-068757; (d) a VH comprising the amino acid sequence of the VH of P1-068759, and a VL comprising the amino acid sequence of the VL of P1-068759; (e) VH comprising the amino acid sequence of VH of P1-068761, and VL comprising the amino acid sequence of VL of P1-068761; (f) VH comprising the amino acid sequence of VH of P1-068763, and VL comprising the amino acid sequence of VL of P1-068763; (g) VH comprising the amino acid sequence of VH of P1-068765, and VL comprising the amino acid sequence of VL of P1-068765; (h) VH comprising the amino acid sequence of VH of P1-068767, and VL comprising the amino acid sequence of VL of P1-068767; (i) a VH comprising the amino acid sequence of the VH of P1-068769, and a VL comprising the amino acid sequence of the VL of P1-068769; (j) VH comprising the amino acid sequence of VH of P1-068771, and VL comprising the amino acid sequence of VL of P1-068771; (k) VH comprising the amino acid sequence of VH of P1-068773, and VL comprising the amino acid sequence of VL of -068773; (l) VH comprising the amino acid sequence of VH of P1-068775, and VL comprising the amino acid sequence of VL of P1-068775; (m) a VH comprising the amino acid sequence of the VH of P1-069059, and a VL comprising the amino acid sequence of the VL of P1-069059; (n) a VH comprising the amino acid sequence of the VH of P1-069061, and a VL comprising the amino acid sequence of the VL of P1-069061; (o) VH comprising the amino acid sequence of VH of P1-069063, and VL comprising the amino acid sequence of VL of P1-069063; (p) VH comprising the amino acid sequence of VH of P1-069065, and VL comprising the amino acid sequence of VL of P1-069065; (q) a VH comprising the amino acid sequence of the VH of P1-069067, and a VL comprising the amino acid sequence of the VL of P1-069067; (r) VH comprising the amino acid sequence of VH of P1-069069, and VL comprising the amino acid sequence of VL of P1-069069; (s) a VH comprising the amino acid sequence of the VH of P1-069071, and a VL comprising the amino acid sequence of the VL of P1-069071; (t) VH comprising the amino acid sequence of VH of P1-069073, and VL comprising the amino acid sequence of VL of P1-069073; (u) VH comprising the amino acid sequence of VH of P1-069075, and VL comprising the amino acid sequence of VL of P1-069075; (v) VH comprising the amino acid sequence of VH of P1-069077, and VL comprising the amino acid sequence of VL of P1-069077; (w) VH comprising the amino acid sequence of VH of P1-068736, and VL comprising the amino acid sequence of VL of P1-068736; (x) VH comprising the amino acid sequence of VH of P1-068738, and VL comprising the amino acid sequence of VL of P1-068738; (y) VH comprising the amino acid sequence of VH of P1-068740, and VL comprising the amino acid sequence of VL of P1-068740; (z) VH comprising the amino acid sequence of VH of P1-068742, and VL comprising the amino acid sequence of VL of P1-068742; (aa) VH comprising the amino acid sequence of VH of P1-068744, and VL comprising the amino acid sequence of VL of P1-068744; (bb) VH comprising the amino acid sequence of VH of P1-068746, and VL comprising the amino acid sequence of VL of P1-068746; (cc) VH comprising the amino acid sequence of VH of P1-068748, and VL comprising the amino acid sequence of VL of P1-068748; (dd) VH comprising the amino acid sequence of VH of P1-068750, and VL comprising the amino acid sequence of VL of P1-068750; (ee) VH comprising the amino acid sequence of VH of P1-068752, and VL comprising the amino acid sequence of VL of P1-068752; (ff) VH comprising the amino acid sequence of VH of P1-068754, and VL comprising the amino acid sequence of VL of P1-068754; (gg) VH comprising the amino acid sequence of VH of P1-068761_E55A, and VL comprising the amino acid sequence of VL of P1-068761_E55A; (hh) VH comprising the amino acid sequence of VH of P1-068761_H100G, and VL comprising the amino acid sequence of VL of P1-068761_H100G; (ii) a VH comprising the amino acid sequence of the VH of P1-068761_E56N, and a VL comprising the amino acid sequence of the VL of P1-068761_E56N; (jj) VH comprising the amino acid sequence of VH of P1-068761_E55A_E56N, and VL comprising the amino acid sequence of VL of P1-068761_E55A_E56N; (kk) VH comprising the amino acid sequence of VH of P1-068761_E30D, and VL comprising the amino acid sequence of VL of P1-068761_E30D; (ll) VH comprising the amino acid sequence of VH of P1-068761_E30D_E55A, and VL comprising the amino acid sequence of VL of P1-068761_E30D_E55A; (mm) VH comprising the amino acid sequence of VH of P1-068761_E56N_H100G, and VL comprising the amino acid sequence of VL of P1-068761_E56N_H100G; (nn) VH comprising the amino acid sequence of VH of P1-068761_E30D_H100G, and VL comprising the amino acid sequence of VL of P1-068761_E30D_H100G; (oo) VH comprising the amino acid sequence of VH of P1-068761_E30D_E56N, and VL comprising the amino acid sequence of VL of P1-068761_E30D_E56N; (pp) VH comprising the amino acid sequence of VH of P1-068761_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_E100fF; (qq) VH comprising the amino acid sequence of VH of P1-068761_E55A_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_E55A_E100fF; (rr) VH comprising the amino acid sequence of VH of P1-068761_H100G_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_H100G_E100fF; (ss) VH comprising the amino acid sequence of VH of P1-068761_E30D_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_E30D_E100fF; (tt) VH comprising the amino acid sequence of VH of P1-068761_E56N_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_E56N_E100fF; (uu) VH comprising the amino acid sequence of VH of P1-068761_E32Y, and VL comprising the amino acid sequence of VL of P1-068761_E32Y; (vv) VH comprising the amino acid sequence of VH of P1-068761_E32Y_E55A, and VL comprising the amino acid sequence of VL of P1-068761_E32Y_E55A; (ww) VH comprising the amino acid sequence of VH of P1-068761_E32Y_E56N, and VL comprising the amino acid sequence of VL of P1-068761_E32Y_E56N; (xx) VH comprising the amino acid sequence of VH of P1-068761_E30D_E32Y, and VL comprising the amino acid sequence of VL of P1-068761_E30D_E32Y; (yy) VH comprising the amino acid sequence of VH of P1-068761_E32Y_H100G, and VL comprising the amino acid sequence of VL of P1-068761_E32Y_H100G; (zz) VH comprising the amino acid sequence of VH of P1-068761_E32Y_E100fF, and VL comprising the amino acid sequence of VL of P1-068761_E32Y_E100fF; (aaa) VH comprising the amino acid sequence of VH of P1-068767_D52N_D102V, and VL comprising the amino acid sequence of VL of P1-068767_D52N_D102V; (bbb) VH comprising the amino acid sequence of VH of P1-068767_D52N, and VL comprising the amino acid sequence of VL of P1-068767_D52N; (ccc) VH comprising the amino acid sequence of VH of P1-068767_D52N_E55A, and VL comprising the amino acid sequence of VL of P1-068767_D52N_E55A; (ddd) VH comprising the amino acid sequence of VH of P1-068767_E55A_D102V, and VL comprising the amino acid sequence of VL of P1-068767_E55A_D102V; (eee) VH comprising the amino acid sequence of VH of P1-068767_D102V, and VL comprising the amino acid sequence of VL of P1-068767_D102V; (fff) VH comprising the amino acid sequence of VH of P1-068767_E55A, and VL comprising the amino acid sequence of VL of P1-068767_E55A; (ggg) VH comprising the amino acid sequence of VH of P1-068767_E30D_D52N, and VL comprising the amino acid sequence of VL of P1-068767_E30D_D52N; (hhh) VH comprising the amino acid sequence of VH of P1-068767_E30D_D102V, and VL comprising the amino acid sequence of VL of P1-068767_E30D_D102V; (iii) VH comprising the amino acid sequence of VH of P1-068767_E30D, and VL comprising the amino acid sequence of VL of P1-068767_E30D; (jjj) VH comprising the amino acid sequence of VH of P1-068767_E30D_E55A, and VL comprising the amino acid sequence of VL of P1-068767_E30D_E55A; (kkk) VH comprising the amino acid sequence of VH of P1-068767_E100fF_D102V, and VL comprising the amino acid sequence of VL of P1-068767_E100fF_D102V; (lll) VH comprising the amino acid sequence of VH of P1-068767_E55A_E100fF, and VL comprising the amino acid sequence of VL of P1-068767_E55A_E100fF; (mmm) VH comprising the amino acid sequence of VH of P1-068767_D52N_E100fF, and VL comprising the amino acid sequence of VL of P1-068767_D52N_E100fF; (nnn) VH comprising the amino acid sequence of VH of P1-068767_E100fF, and VL comprising the amino acid sequence of VL of P1-068767_E100fF; or (ooo) VH comprising the amino acid sequence of VH of P1-068767_E30D_E100fF, and VL comprising the amino acid sequence of VL of P1-068767_E30D_E100fF may also include:

[0086] Anti-hVISTA Ab (a) a VH comprising the VH CDRs of the VH of P1-061029, a VL comprising the VL CDRs of P1-061029, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-061029; (b) a VH comprising the VH CDRs of the VH of P1-061015, a VL comprising the VL CDRs of P1-061015, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-061015; (c) a VH comprising the VH CDRs of the VH of P1-068757, a VL comprising the VL CDRs of P1-068757, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068757; (d) a VH comprising the VH CDRs of the VH of P1-068759, a VL comprising the VL CDRs of P1-068759, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068759; (e) a VH comprising the VH CDRs of the VH of P1-068761, a VL comprising the VL CDRs of P1-068761, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068761; (f) a VH comprising the VH CDRs of the VH of P1-068763, a VL comprising the VL CDRs of P1-068763, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068763; (g) a VH comprising the VH CDRs of the VH of P1-068765, a VL comprising the VL CDRs of P1-068765, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068765; (h) a VH comprising the VH CDRs of the VH of P1-068767, a VL comprising the VL CDRs of P1-068767, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068767; (i) a VH comprising the VH CDRs of the VH of P1-068769, a VL comprising the VL CDRs of P1-068769, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068769; (j) a VH comprising the VH CDRs of the VH of P1-068771, a VL comprising the VL CDRs of P1-068771, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068771; (k) a VH comprising the VH CDRs of the VH of P1-068773, a VL comprising the VL CDRs of P1-068773, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068773; (l) a VH comprising the VH CDRs of the VH of P1-068775, a VL comprising the VL CDRs of P1-068775, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068775; (m) a VH comprising the VH CDRs of the VH of P1-069059, a VL comprising the VL CDRs of P1-069059, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069059; (n) a VH comprising the VH CDRs of the VH of P1-069061, a VL comprising the VL CDRs of P1-069061, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069061; (o) a VH comprising the VH CDRs of the VH of P1-069063, a VL comprising the VL CDRs of P1-069063, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069063; (p) a VH comprising the VH CDRs of the VH of P1-069065, a VL comprising the VL CDRs of P1-069065, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069065; (q) a VH comprising the VH CDRs of the VH of P1-069067, a VL comprising the VL CDRs of P1-069067, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069067; (r) a VH comprising the VH CDRs of the VH of P1-069069, a VL comprising the VL CDRs of P1-069069, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069069; (s) a VH comprising the VH CDRs of the VH of P1-069071, a VL comprising the VL CDRs of P1-069071, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-069071; (t) a VH comprising the VH CDRs of the VH of P1-069073, a VL comprising the VL CDRs of P1-069073, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069073; (u) a VH comprising the VH CDRs of the VH of P1-069075, a VL comprising the VL CDRs of P1-069075, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-069075; (v) a VH comprising the VH CDRs of the VH of P1-069077, a VL comprising the VL CDRs of P1-069077, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-069077; (w) a VH comprising the VH CDRs of the VH of P1-068736, a VL comprising the VL CDRs of P1-068736, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068736; (x) a VH comprising the VH CDRs of the VH of P1-068738, a VL comprising the VL CDRs of P1-068738, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068738; (y) a VH comprising the VH CDRs of the VH of P1-068740, a VL comprising the VL CDRs of P1-068740, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068740; (z) a VH comprising the VH CDRs of the VH of P1-068742, a VL comprising the VL CDRs of P1-068742, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068742; (aa) a VH comprising the VH CDRs of the VH of P1-068744, a VL comprising the VL CDRs of P1-068744, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068744; (bb) a VH comprising the VH CDRs of the VH of P1-068746, a VL comprising the VL CDRs of P1-068746, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068746; (cc) a VH comprising the VH CDRs of the VH of P1-068748, a VL comprising the VL CDRs of P1-068748, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068748; (dd) a VH comprising the VH CDRs of the VH of P1-068750, a VL comprising the VL CDRs of P1-068750, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068750; (ee) a VH comprising the VH CDRs of the VH of P1-068752, a VL comprising the VL CDRs of P1-068752, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068752; (ff) a VH comprising the VH CDRs of the VH of P1-068754, a VL comprising the VL CDRs of P1-068754, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068754; (gg) a VH comprising the VH CDRs of the VH of P1-068761_E55A, a VL comprising the VL CDRs of P1-068761_E55A, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E55A; (hh) a VH comprising the VH CDRs of the VH of P1-068761_H100G, a VL comprising the VL CDRs of P1-068761_H100G, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_H100G; (ii) a VH comprising the VH CDRs of the VH of P1-068761_E56N, a VL comprising the VL CDRs of P1-068761_E56N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E56N; (jj) a VH comprising the VH CDRs of the VH of P1-068761_E55A_E56N, a VL comprising the VL CDRs of P1-068761_E55A_E56N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E55A_E56N; (kk) a VH comprising the VH CDRs of the VH of P1-068761_E30D, a VL comprising the VL CDRs of P1-068761_E30D, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D; (ll) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E55A, a VL comprising the VL CDRs of P1-068761_E30D_E55A, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D_E55A; (mm) a VH comprising the VH CDRs of the VH of P1-068761_E56N_H100G, a VL comprising the VL CDRs of P1-068761_E56N_H100G, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E56N_H100G; (nn) a VH comprising the VH CDRs of the VH of P1-068761_E30D_H100G, a VL comprising the VL CDRs of P1-068761_E30D_H100G, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D_H100G; (oo) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E56N, a VL comprising the VL CDRs of P1-068761_E30D_E56N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D_E56N; (pp) a VH comprising the VH CDRs of the VH of P1-068761_E100fF, a VL comprising the VL CDRs of P1-068761_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E100fF; (qq) a VH comprising the VH CDRs of the VH of P1-068761_E55A_E100fF, a VL comprising the VL CDRs of P1-068761_E55A_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E55A_E100fF; (rr) a VH comprising the VH CDRs of the VH of P1-068761_H100G_E100fF, a VL comprising the VL CDRs of P1-068761_H100G_E100fF, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068761_H100G_E100fF; (ss) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E100fF, a VL comprising the VL CDRs of P1-068761_E30D_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D_E100fF; (tt) a VH comprising the VH CDRs of the VH of P1-068761_E56N_E100fF, a VL comprising the VL CDRs of P1-068761_E56N_E100fF, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068761_E56N_E100fF; (uu) a VH comprising the VH CDRs of the VH of P1-068761_E32Y, a VL comprising the VL CDRs of P1-068761_E32Y, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E32Y; (vv) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_E55A, a VL comprising the VL CDRs of P1-068761_E32Y_E55A, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068761_E32Y_E55A; (ww) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_E56N, a VL comprising the VL CDRs of P1-068761_E32Y_E56N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E32Y_E56N; (xx) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E32Y, a VL comprising the VL CDRs of P1-068761_E30D_E32Y, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E30D_E32Y; (yy) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_H100G, a VL comprising the VL CDRs of P1-068761_E32Y_H100G, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E32Y_H100G; (zz) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_E100fF, a VL comprising the VL CDRs of P1-068761_E32Y_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068761_E32Y_E100fF; (aaa) a VH comprising the VH CDRs of the VH of P1-068767_D52N_D102V, a VL comprising the VL CDRs of P1-068767_D52N_D102V, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_D52N_D102V; (bbb) a VH comprising the VH CDRs of the VH of P1-068767_D52N, a VL comprising the VL CDRs of P1-068767_D52N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_D52N; (ccc) a VH comprising the VH CDRs of the VH of P1-068767_D52N_E55A, a VL comprising the VL CDRs of P1-068767_D52N_E55A, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_D52N_E55A; (ddd) a VH comprising the VH CDRs of the VH of P1-068767_E55A_D102V, a VL comprising the VL CDRs of P1-068767_E55A_D102V, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E55A_D102V; (eee) a VH comprising the VH CDRs of the VH of P1-068767_D102V, a VL comprising the VL CDRs of P1-068767_D102V, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_D102V; (fff) a VH comprising the VH CDRs of the VH of P1-068767_E55A, a VL comprising the VL CDRs of P1-068767_E55A, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E55A; (ggg) a VH comprising the VH CDRs of the VH of P1-068767_E30D_D52N, a VL comprising the VL CDRs of P1-068767_E30D_D52N, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E30D_D52N; (hhh) a VH comprising the VH CDRs of the VH of P1-068767_E30D_D102V, a VL comprising the VL CDRs of P1-068767_E30D_D102V, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E30D_D102V; (iii) a VH comprising the VH CDRs of the VH of P1-068767_E30D, a VL comprising the VL CDRs of P1-068767_E30D, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E30D; (jjj) a VH comprising the VH CDRs of the VH of P1-068767_E30D_E55A, a VL comprising the VL CDRs of P1-068767_E30D_E55A, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E30D_E55A; (kkk) A VH comprising the VH CDR of the VH of P1-068767_E100fF_D102V, a VL comprising the VL CDR of P1-068767_E100fF_D102V, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E100fF_D102V; (lll) a VH comprising the VH CDRs of the VH of P1-068767_E55A_E100fF, a VL comprising the VL CDRs of P1-068767_E55A_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E55A_E100fF; (mmm) a VH comprising the VH CDRs of the VH of P1-068767_D52N_E100fF, a VL comprising the VL CDRs of P1-068767_D52N_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_D52N_E100fF; (nnn) a VH comprising the VH CDRs of the VH of P1-068767_E100fF, a VL comprising the VL CDRs of P1-068767_E100fF, and a VH and VL amino acid sequence that is 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% identical to the VH and VL of P1-068767_E100fF; or (ooo) A VH comprising the VH CDRs of the VH of P1-068767_E30D_E100fF, and a VL comprising the VL CDRs of P1-068767_E30D_E100fF, and VH and VL amino acid sequences that are 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% identical to the VH and VL of P1-068767_E30D_E100fF. may also include:

[0087] Anti-hVISTA Ab (a) VH consisting of the amino acid sequence of VH of P1-061029 and VL consisting of VL of P1-061029; (b) VH consisting of the amino acid sequence of VH of P1-061015 and VL consisting of VL of P1-061015; (c) VH consisting of the amino acid sequence of VH of P1-068757 and VL consisting of VL of P1-068757; (d) a VH consisting of the amino acid sequence of the VH of P1-068759, and a VL consisting of the VL of P1-068759; (e) VH consisting of the amino acid sequence of VH of P1-068761, and VL consisting of VL of P1-068761; (f) VH consisting of the amino acid sequence of VH of P1-068763, and VL consisting of VL of P1-068763; (g) VH consisting of the amino acid sequence of VH of P1-068765, and VL consisting of VL of P1-068765; (h) VH consisting of the amino acid sequence of VH of P1-068767, and VL consisting of VL of P1-068767; (i) a VH consisting of the amino acid sequence of the VH of P1-068769, and a VL consisting of the VL of P1-068769; (j) VH consisting of the amino acid sequence of VH of P1-068771 and VL consisting of VL of P1-068771; (k) VH consisting of the amino acid sequence of VH of P1-068773, and VL consisting of VL of P1-068773; (l) VH consisting of the amino acid sequence of VH of P1-068775, and VL consisting of VL of P1-068775; (m) a VH consisting of the amino acid sequence of the VH of P1-069059, and a VL consisting of the VL of P1-069059; (n) a VH consisting of the amino acid sequence of the VH of P1-069061, and a VL consisting of the VL of P1-069061; (o) VH consisting of the amino acid sequence of VH of P1-069063, and VL consisting of VL of P1-069063; (p) VH consisting of the amino acid sequence of VH of P1-069065, and VL consisting of VL of P1-069065; (q) a VH consisting of the amino acid sequence of the VH of P1-069067, and a VL consisting of the VL of P1-069067; (r) VH consisting of the amino acid sequence of VH of P1-069069, and VL consisting of VL of P1-069069; (s) a VH consisting of the amino acid sequence of the VH of P1-069071, and a VL consisting of the VL of P1-069071; (t) VH consisting of the amino acid sequence of VH of P1-069073, and VL consisting of VL of P1-069073; (u) VH consisting of the amino acid sequence of VH of P1-069075, and VL consisting of VL of P1-069075; (v) VH consisting of the amino acid sequence of VH of P1-069077, and VL consisting of VL of P1-069077; (w) VH consisting of the amino acid sequence of VH of P1-068736 and VL consisting of VL of P1-068736; (x) VH consisting of the amino acid sequence of VH of P1-068738, and VL consisting of VL of P1-068738; (y) VH consisting of the amino acid sequence of VH of P1-068740, and VL consisting of VL of P1-068740; (z) VH consisting of the amino acid sequence of VH of P1-068742 and VL consisting of VL of P1-068742; (aa) VH consisting of the amino acid sequence of VH of P1-068744, and VL consisting of VL of P1-068744; (bb) VH consisting of the amino acid sequence of VH of P1-068746 and VL consisting of VL of P1-068746; (cc) VH consisting of the amino acid sequence of VH of P1-068748, and VL consisting of VL of P1-068748; (dd) VH consisting of the amino acid sequence of VH of P1-068750, and VL consisting of VL of P1-068750; (ee) VH consisting of the amino acid sequence of VH of P1-068752, and VL consisting of VL of P1-068752; (ff) VH consisting of the amino acid sequence of VH of P1-068754, and VL consisting of VL of P1-068754; (gg) VH consisting of the amino acid sequence of VH of P1-068761_E55A, and VL consisting of the amino acid sequence of VL of P1-068761_E55A; (hh) VH consisting of the amino acid sequence of VH of P1-068761_H100G, and VL consisting of the amino acid sequence of VL of P1-068761_H100G; (ii) VH consisting of the amino acid sequence of VH of P1-068761_E56N, and VL consisting of the amino acid sequence of VL of P1-068761_E56N; (jj) VH consisting of the amino acid sequence of VH of P1-068761_E55A_E56N, and VL consisting of the amino acid sequence of VL of P1-068761_E55A_E56N; (kk) VH consisting of the amino acid sequence of VH of P1-068761_E30D, and VL consisting of the amino acid sequence of VL of P1-068761_E30D; (ll) VH consisting of the amino acid sequence of VH of P1-068761_E30D_E55A, and VL consisting of the amino acid sequence of VL of P1-068761_E30D_E55A; (mm) VH consisting of the amino acid sequence of VH of P1-068761_E56N_H100G, and VL consisting of the amino acid sequence of VL of P1-068761_E56N_H100G; (nn) VH consisting of the amino acid sequence of VH of P1-068761_E30D_H100G, and VL consisting of the amino acid sequence of VL of P1-068761_E30D_H100G; (oo) VH consisting of the amino acid sequence of VH of P1-068761_E30D_E56N, and VL consisting of the amino acid sequence of VL of P1-068761_E30D_E56N; (pp) VH consisting of the amino acid sequence of VH of P1-068761_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_E100fF; (qq) VH consisting of the amino acid sequence of VH of P1-068761_E55A_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_E55A_E100fF; (rr) VH consisting of the amino acid sequence of VH of P1-068761_H100G_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_H100G_E100fF; (ss) VH consisting of the amino acid sequence of VH of P1-068761_E30D_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_E30D_E100fF; (tt) VH consisting of the amino acid sequence of VH of P1-068761_E56N_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_E56N_E100fF; (uu) VH consisting of the amino acid sequence of VH of P1-068761_E32Y, and VL consisting of the amino acid sequence of VL of P1-068761_E32Y; (vv) VH consisting of the amino acid sequence of VH of P1-068761_E32Y_E55A, and VL consisting of the amino acid sequence of VL of P1-068761_E32Y_E55A; (ww) VH consisting of the amino acid sequence of VH of P1-068761_E32Y_E56N, and VL consisting of the amino acid sequence of VL of P1-068761_E32Y_E56N; (xx) VH consisting of the amino acid sequence of VH of P1-068761_E30D_E32Y, and VL consisting of the amino acid sequence of VL of P1-068761_E30D_E32Y; (yy) VH consisting of the amino acid sequence of VH of P1-068761_E32Y_H100G, and VL consisting of the amino acid sequence of VL of P1-068761_E32Y_H100G; (zz) VH consisting of the amino acid sequence of VH of P1-068761_E32Y_E100fF, and VL consisting of the amino acid sequence of VL of P1-068761_E32Y_E100fF; (aaa) VH consisting of the amino acid sequence of VH of P1-068767_D52N_D102V, and VL consisting of the amino acid sequence of VL of P1-068767_D52N_D102V; (bbb) VH consisting of the amino acid sequence of VH of P1-068767_D52N, and VL consisting of the amino acid sequence of VL of P1-068767_D52N; (ccc) VH consisting of the amino acid sequence of VH of P1-068767_D52N_E55A, and VL consisting of the amino acid sequence of VL of P1-068767_D52N_E55A; (ddd) VH consisting of the amino acid sequence of VH of P1-068767_E55A_D102V, and VL consisting of the amino acid sequence of VL of P1-068767_E55A_D102V; (eee) VH consisting of the amino acid sequence of VH of P1-068767_D102V, and VL consisting of the amino acid sequence of VL of P1-068767_D102V; (fff) VH consisting of the amino acid sequence of VH of P1-068767_E55A, and VL consisting of the amino acid sequence of VL of P1-068767_E55A; (ggg) VH consisting of the amino acid sequence of VH of P1-068767_E30D_D52N, and VL consisting of the amino acid sequence of VL of P1-068767_E30D_D52N; (hhh) VH consisting of the amino acid sequence of VH of P1-068767_E30D_D102V, and VL consisting of the amino acid sequence of VL of P1-068767_E30D_D102V; (iii) VH consisting of the amino acid sequence of VH of P1-068767_E30D, and VL consisting of the amino acid sequence of VL of P1-068767_E30D; (jjj) VH consisting of the amino acid sequence of VH of P1-068767_E30D_E55A, and VL consisting of the amino acid sequence of VL of P1-068767_E30D_E55A; (kkk) VH consisting of the amino acid sequence of VH of P1-068767_E100fF_D102V, and VL consisting of the amino acid sequence of VL of P1-068767_E100fF_D102V; (lll) VH consisting of the amino acid sequence of VH of P1-068767_E55A_E100fF, and VL consisting of the amino acid sequence of VL of P1-068767_E55A_E100fF; (mmm) VH consisting of the amino acid sequence of VH of P1-068767_D52N_E100fF, and VL consisting of the amino acid sequence of VL of P1-068767_D52N_E100fF; (nnn) VH consisting of the amino acid sequence of VH of P1-068767_E100fF, and VL consisting of the amino acid sequence of VL of P1-068767_E100fF; or (ooo) VH comprising the amino acid sequence of VH of P1-068767_E30D_E100fF, and VL comprising the amino acid sequence of VL of P1-068767_E30D_E100fF may also include:

[0088] In certain embodiments, the anti-VISTA Ab P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-0687 69, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-0 69067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P 1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752 P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30 D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF. (1) one or more of VH CDR1, CDR2, and CDR3; (2) VH CDR1, CDR2, and CDR3; (3) VH, (4) one or more of VH CDR1, CDR2, and CDR3, and one or more of VL CDR1, CDR2, and CDR3; (5) VH CDR1, CDR2, and CDR3, and VL CDR1, CDR2, and CDR3; or (6) VH and VL The anti-VISTA Ab may comprise any of the variable regions and / or variable region CDRs 1-3 of the antibodies described above and elsewhere herein, such as, for example, VISTA ...

[0089] In certain embodiments, the anti-VISTA Ab P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-0 69067、P1-069069、P1-069071、P1-069073、P1-069075、P1-069077、P1-061015、P1-068736、P1-068738、P1-068740、P1-068742、P1-068744、P1-068766、P1-068748、P1-068750、P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_ E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N , P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P 1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E 30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52 N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30 D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF, (1) one or more of VH CDR1, CDR2, and CDR3; (2) VH CDR1, CDR2, and CDR3; (3) VH, (4) one or more of VH CDR1, CDR2, and CDR3, and one or more of VL CDR1, CDR2, and CDR3; (5) VH CDR1, CDR2, and CDR3, and VL CDR1, CDR2, and CDR3; or (6) VH and VL and / or any of the variable regions CDR1-3 of the antibodies described above and elsewhere herein, such as Further comprising one or more of the following characteristics: - specifically binds to hVISTA at an acidic pH, e.g., pH 6.0 or pH 6.5, e.g., to a polypeptide comprising the histidine-rich region of the ECD or amino acid residues 35 to 127 of SEQ ID NO: 2; - lacking significant binding to hVISTA at physiological or neutral pH, e.g., pH 7.4 or pH 7.0, e.g., to a polypeptide comprising the histidine-rich region of the ECD or amino acid residues 35 to 127 of SEQ ID NO: 2; - specifically binds to cynoVISTA, e.g., to the histidine-rich region of the ECD, at an acidic pH, e.g., at pH 6.0 or pH 6.5; - lacking significant binding to cyno VISTA, e.g., to the histidine-rich region of the ECD, at physiological or neutral pH, e.g., pH 7.4 or pH 7.0; - has reduced binding to hVISTA-ECD having a substitution at one or more of the following amino acids: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127 compared to hVISTA ECD having SEQ ID NO: 2; - cross-compete with P1-061029, P1-068761, P1-068767, and / or P1-061015 for binding to hVISTA; - inhibiting binding of hVISTA to human T cells at an acidic pH, e.g., pH 6.0 or pH 6.5; - inhibiting the binding of hVISTA to PSGL-1 at an acidic pH, e.g., pH 6.0 or pH 6.5; - a mean residence time of at least 350 hours in cynomolgus monkeys, - stimulating T cell activation; - inhibiting VISTA-mediated cell-cell adhesion, and - specifically binds to hVISTA in a sample of human tumor cells or in a sample of inflamed human tissue.

[0090] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain (HC) comprising the amino acid sequence of the heavy chain of any of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is selected from the group consisting of P1-061029.IgG1.3 (SEQ ID NO: 69), P1-068757.IgG1.3, P1-068759.IgG1.3, P1-068761.IgG1.3, P1-068763.IgG1.3, P1-068765.IgG1.3, P1-068767.IgG1.3, P1-068769.IgG1.3, P1-068771.IgG1.3, P1-068773.IgG1.3, P1-068775.IgG1.3, P1-069059.IgG1.3, P1-0690 61.IgG1.3, P1-069063.IgG1.3, P1-069065.IgG1.3, P1-069067.IgG1.3, P1-069069.IgG1.3, P1-069071.IgG1.3, P1-069073.IgG1.3 , P1-069075.IgG1.3, P1-069077.IgG1.3, P1-061015.IgG1.3, P1-068736.IgG1.3, P1-068738.IgG1.3, P1-068740.IgG1.3, P1-068742 .IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1.3, P1-068752.IgG1.3, P1-068754.IgG1.3, P 1-068761_E55A.IgG1.3, P1-068761_H100G.IgG1.3, P1-068761_E56N.IgG1.3, P1-068761_E55A_E56N.IgG1.3, P1-068761_E30D.IgG1 .3, P1-068761_E30D_E55A.IgG1.3, P1-068761_E56N_H100G.IgG1.3, P1-068761_E30D_H100G.IgG1.3, P1-068761_E30D_E56N.IgG1. 3, P1-068761_E100fF.IgG1.3, P1-068761_E55A_E100fF.IgG1.3, P1-068761_H100G_E100fF.IgG1.3, P1-068761_E30D_E100fF.IgG1.3, P1-068761_E56N_E100fF.IgG1.3, P1-068761_E32Y.IgG1.3, P1-068761_E32Y_E55A.IgG1.3, P1-0 68761_E32Y_E56N.IgG1.3, P1-068761_E30D_E32Y.IgG1.3, P1-068761_E32Y_H100G.IgG1.3, P1-068 761_E32Y_E100fF.IgG1.3, P1-068767_D52N_D102V.IgG1.3, P1-068767_D52N.IgG1.3, P1-068767_D 52N_E55A.IgG1.3, P1-068767_E55A_D102V.IgG1.3, P1-068767_D102V.IgG1.3, P1-068767_E55A.Ig G1.3, P1-068767_E30D_D52N.IgG1.3, P1-068767_E30D_D102V.IgG1.3, P1-068767_E30D.IgG1.3, P1 -068767_E30D_E55A.IgG1.3, P1-068767_E100fF_D102V.IgG1.3, P1-068767_E55A_E100fF.IgG1.3, and a heavy chain comprising the amino acid sequence of the heavy chain of P1-061029 or P1-061015 or a progeny thereof as set forth in the Sequence Listing below, including an IgG1.3 heavy chain constant region, such as P1-068767_D52N_E100fF.IgG1.3, P1-068767_E100fF.IgG1.3, or P1-068767_E30D_E100fF.IgG1.3.

[0091] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain comprising the amino acid sequence of the heavy chain of any of the anti-hVISTA Abs provided herein, including the IgG1.3 heavy chain constant region, and the amino acid sequence of the light chain of any of the anti-hVISTA Abs provided herein. The Abs are P1-061029.IgG1.3 (SEQ ID NO: 69), P1-068757.IgG1.3, P1-068759.IgG1.3, P1-068761.IgG1.3, P1-068763.IgG1.3, P1-068765.IgG1.3, P1-068767.IgG1.3, P1-068769.IgG1.3, P1-068771.IgG1.3, P1-068773.IgG1.3, P1-068775.IgG1.3, P1-069059 .IgG1.3, P1-069061.IgG1.3, P1-069063.IgG1.3, P1-069065.IgG1.3, P1-069067.IgG1.3, P1-069069.IgG1.3, P1-069071.I gG1.3, P1-069073.IgG1.3, P1-069075.IgG1.3, P1-069077.IgG1.3, P1-061015.IgG1.3, P1-068736.IgG1.3, P1-068738.IgG 1.3, P1-068740.IgG1.3, P1-068742.IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1. 3, P1-068752.IgG1.3, P1-068754.IgG1.3, P1-068761_E55A.IgG1.3, P1-068761_H100G.IgG1.3, P1-068761_E56N.IgG1.3, P 1-068761_E55A_E56N.IgG1.3, P1-068761_E30D.IgG1.3, P1-068761_E30D_E55A.IgG1.3, P1-068761_E56N_H100G.IgG1.3, P 1-068761_E30D_H100G.IgG1.3, P1-068761_E30D_E56N.IgG1.3, P1-068761_E100fF.IgG1.3, P1-068761_E55A_E100fF.IgG1.3, P1-068761_H100G_E100fF.IgG1.3, P1-068761_E30D_E100fF.IgG1.3, P1-068761_E56N_E100fF.IgG1.3, P1-0 68761_E32Y.IgG1.3, P1-068761_E32Y_E55A.IgG1.3, P1-068761_E32Y_E56N.IgG1.3, P1-068761_E30D_E32Y.Ig G1.3, P1-068761_E32Y_H100G.IgG1.3, P1-068761_E32Y_E100fF.IgG1.3, P1-068767_D52N_D102V.IgG1.3, P1-0 68767_D52N.IgG1.3, P1-068767_D52N_E55A.IgG1.3, P1-068767_E55A_D102V.IgG1.3, P1-068767_D102V.IgG1.3 , P1-068767_E55A.IgG1.3, P1-068767_E30D_D52N.IgG1.3, P1-068767_E30D_D102V.IgG1.3, P1-068767_E30D.I gG1.3, P1-068767_E30D_E55A.IgG1.3, P1-068767_E100fF_D102V.IgG1.3, P1-068767_E55A_E100fF.IgG1.3, P1- and a heavy chain comprising the amino acid sequence of the VH of P1-061029 or P1-061015 or a progeny thereof, including an IgG1.3HC constant region such as 068767_D52N_E100fF.IgG1.3, P1-068767_E100fF.IgG1.3, or P1-068767_E30D_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-061029 or P1-061015.

[0092] Anti-hVISTA Ab (a) a heavy chain comprising the amino acid sequence of the heavy chain of P1-061029.IgG1.3 (SEQ ID NO: 69), and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) a heavy chain comprising the amino acid sequence of the heavy chain of P1-061015.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-061015; (c) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068757.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068757; (d) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068759.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068759; (e) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761; (f) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068763.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068763; (g) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068765.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068765; (h) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767; (i) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068769.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068769; (j) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068771.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068771; (k) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068773.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068773; (l) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068775.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068775; (m) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069059.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069059; (n) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069061.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069061; (o) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069063.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069063; (p) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069065.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069065; (q) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069067.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069067; (r) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069069.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069069; (s) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069071.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069071; (t) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069073.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069073; (u) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069075.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069075; (v) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069077.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-069077; (w) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068736.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068736; (x) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068738.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068738; (y) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068740.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068740; (z) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068742.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068742; (aa) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068744.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068744; (bb) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068746.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068746; (cc) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068748.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068748; (dd) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068750.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068750; (ee) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068752.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068752; (ff) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068754.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068754; (gg) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A; (hh) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_H100G.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G; (ii) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N; (jj) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A_E56N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E56N; (kk) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D; (ll) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E55A; (mm) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N_H100G.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_H100G; (nn) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_H100G.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_H100G; (oo) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E56N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E56N; (pp) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E100fF; (qq) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E100fF; (rr) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_H100G_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G_E100fF; (ss) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E100fF; (tt) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_E100fF; (uu) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y; (vv) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E55A; a heavy chain comprising the amino acid sequence of the heavy chain of (ww)P1-068761_E32Y_E56N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E56N; (xx) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E32Y.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E32Y; (yy) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_H100G.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_H100G; (zz) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E100fF; a heavy chain comprising the amino acid sequence of the heavy chain of (aaa)P1-068767_D52N_D102V.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_D102V; (bbb) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N; (ccc) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E55A; (ddd) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A_D102V.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_D102V; (eee) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D102V.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_D102V; (fff) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A; (ggg) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_D52N.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D52N; (hhh) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_D102V.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D102V; (iii) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D; (jjj) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_E55A.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E55A; (kkk) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E100fF_D102V.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF_D102V, (lll) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_E100fF; (mmm) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E100fF; (nnn) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF, or (ooo) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_E100fF.IgG1.3, and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E100fF. may also include:

[0093] Anti-hVISTA Ab (a) a heavy chain (HC) comprising the HC CDRs of the HC of P1-061029, and a light chain (LC) comprising the LC CDRs of P1-061029, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-061029.IgG1.3, respectively; (b) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P-061015, and a LC comprising the LC CDRs of P1-061015, and the HC and LC of P1-061015.IgG1.3, respectively; (c) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068757, and a LC comprising the LC CDRs of P1-068757, and the HC and LC of P1-068757.IgG1.3, respectively; (d) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068759, and a LC comprising the LC CDRs of P1-068759, and the HC and LC of P1-068759.IgG1.3, respectively; (e) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068761, and a LC comprising the LC CDRs of P1-068761, and the HC and LC of P1-068761.IgG1.3, respectively; (f) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068763, and a LC comprising the LC CDRs of P1-068763, and the HC and LC of P1-068763.IgG1.3, respectively; (g) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068765, and a LC comprising the LC CDRs of P1-068765, and the HC and LC of P1-068765.IgG1.3, respectively; (h) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068767, and a LC comprising the LC CDRs of P1-068767, and the HC and LC of P1-068767.IgG1.3, respectively; (i) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068769, and a LC comprising the LC CDRs of P1-068769, and the HC and LC of P1-068769.IgG1.3, respectively; (j) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068771, and a LC comprising the LC CDRs of P1-068771, and the HC and LC of P1-068771.IgG1.3, respectively; (k) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068773, and a LC comprising the LC CDRs of P1-068773, and the HC and LC of P1-068773.IgG1.3, respectively; (l) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068775, and a LC comprising the LC CDRs of P1-068775, and the HC and LC of P1-068775.IgG1.3, respectively; (m) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069059, and a LC comprising the LC CDRs of P1-069059, and the HC and LC of P1-069059.IgG1.3, respectively; (n) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069061, and a LC comprising the LC CDRs of P1-069061, and the HC and LC of P1-069061.IgG1.3, respectively; (o) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069063, and a LC comprising the LC CDRs of P1-069063, and the HC and LC of P1-069063.IgG1.3, respectively; (p) a HC comprising the HC CDRs of the HC of P1-069065, and a LC comprising the LC CDRs of P1-069065, and a HC and LC that are 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% identical to the HC and LC of P1-069065.IgG1.3, respectively; (q) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069067, and a LC comprising the LC CDRs of P1-069067, and the HC and LC of P1-069067.IgG1.3, respectively; (r) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069069, and a LC comprising the LC CDRs of P1-069069, and the HC and LC of P1-069069.IgG1.3, respectively; (s) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069071, and a LC comprising the LC CDRs of P1-069071, and the HC and LC of P1-069071.IgG1.3, respectively; (t) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069073, and a LC comprising the LC CDRs of P1-069073, and the HC and LC of P1-069073.IgG1.3, respectively; (u) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069075, and a LC comprising the LC CDRs of P1-069075, and the HC and LC of P1-069075.IgG1.3, respectively; (v) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-069077, and a LC comprising the LC CDRs of P1-069077, and the HC and LC of P1-069077.IgG1.3, respectively; (w) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068736, and a LC comprising the LC CDRs of P1-068736, and the HC and LC of P1-068736.IgG1.3, respectively; (x) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068738, and a LC comprising the LC CDRs of P1-068738, and the HC and LC of P1-068738.IgG1.3, respectively; (y) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068740, and a LC comprising the LC CDRs of P1-068740, and the HC and LC of P1-068740.IgG1.3, respectively; (z) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068742, and a LC comprising the LC CDRs of P1-068742, and the HC and LC of P1-068742.IgG1.3, respectively; (aa) a HC comprising the HC CDRs of the HC of P1-068744, and a LC comprising the LC CDRs of P1-068744, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068744.IgG1.3, respectively; (bb) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068746, and a LC comprising the LC CDRs of P1-068746, and the HC and LC of P1-068746.IgG1.3, respectively; (cc) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068748, and a LC comprising the LC CDRs of P1-068748, and the HC and LC of P1-068748.IgG1.3, respectively; (dd) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068750, and a LC comprising the LC CDRs of P1-068750, and the HC and LC of P1-068750.IgG1.3, respectively; (ee) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068752, and a LC comprising the LC CDRs of P1-068752, and the HC and LC of P1-068752.IgG1.3, respectively; (ff) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068754, and a LC comprising the LC CDRs of P1-068754, and the HC and LC of P1-068754.IgG1.3, respectively; (gg) a HC comprising the HC CDRs of the HC of P1-068761_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E55A, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E55A.IgG1.3, respectively; (hh) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068761_H100G.IgG1.3, and a LC comprising the LC CDRs of P1-068761_H100G, and the HC and LC of P1-068761_H100G.IgG1.3, respectively; (ii) a HC comprising the HC CDRs of the HC of P1-068761_E56N.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E56N, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E56N.IgG1.3, respectively; (jj) a HC comprising the HC CDRs of the HC of P1-068761_E55A_E56N.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E55A_E56N, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E55A_E56N.IgG1.3, respectively; (kk) a HC comprising the HC CDRs of the HC of P1-068761_E30D.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E30D.IgG1.3, respectively; (ll) a HC comprising the HC CDRs of the HC of P1-068761_E30D_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D_E55A, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E30D_E55A.IgG1.3, respectively; (mm) a HC comprising the HC CDRs of the HC of P1-068761_E56N_H100G.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E56N_H100G, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E56N_H100G.IgG1.3, respectively; (nn) a HC comprising the HC CDRs of the HC of P1-068761_E30D_H100G.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D_H100G, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E30D_H100G.IgG1.3, respectively; (oo) a HC comprising the HC CDRs of the HC of P1-068761_E30D_E56N.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D_E56N, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E30D_E56N.IgG1.3, respectively; (pp) a HC comprising the HC CDRs of the HC of P1-068761_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E100fF, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E100fF.IgG1.3, respectively; (qq) a HC comprising the HC CDRs of the HC of P1-068761_E55A_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E55A_E100fF, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E55A_E100fF.IgG1.3, respectively; (rr) a HC comprising the HC CDRs of the HC of P1-068761_H100G_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_H100G_E100fF, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_H100G_E100fF.IgG1.3, respectively; (ss) a HC comprising the HC CDRs of the HC of P1-068761_E30D_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D_E100fF, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E30D_E100fF.IgG1.3, respectively; (tt) a HC comprising the HC CDRs of the HC of P1-068761_E56N_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E56N_E100fF, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E56N_E100fF.IgG1.3, respectively; (uu) a HC comprising the HC CDRs of the HC of P1-068761_E32Y.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E32Y, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E32Y.IgG1.3, respectively; (vv) a HC comprising the HC CDRs of the HC of P1-068761_E32Y_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E32Y_E55A, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E32Y_E55A.IgG1.3, respectively; (ww) a HC comprising the HC CDRs of the HC of P1-068761_E32Y_E56N.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E32Y_E56N, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E32Y_E56N.IgG1.3, respectively; (xx) a HC comprising the HC CDRs of the HC of P1-068761_E30D_E32Y.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E30D_E32Y, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E30D_E32Y.IgG1.3, respectively; (yy) a HC comprising the HC CDRs of the HC of P1-068761_E32Y_H100G.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E32Y_H100G, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068761_E32Y_H100G.IgG1.3, respectively; (zz) a HC comprising the HC CDRs of the HC of P1-068761_E32Y_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068761_E32Y_E100fF, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068761_E32Y_E100fF.IgG1.3, respectively; (aaa) a HC comprising the HC CDRs of the HC of P1-068767_D52N_D102V.IgG1.3, and a LC comprising the LC CDRs of P1-068767_D52N_D102V, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068767_D52N_D102V.IgG1.3, respectively; (bbb) a HC comprising the HC CDRs of the HC of P1-068767_D52N.IgG1.3, and a LC comprising the LC CDRs of P1-068767_D52N, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_D52N.IgG1.3, respectively; (ccc) a HC comprising the HC CDRs of the HC of P1-068767_D52N_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068767_D52N_E55A, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_D52N_E55A.IgG1.3, respectively; (ddd) a HC comprising the HC CDRs of the HC of P1-068767_E55A_D102V.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E55A_D102V, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E55A_D102V.IgG1.3, respectively; (eee) a HC comprising the HC CDRs of the HC of P1-068767_D102V.IgG1.3, and a LC comprising the LC CDRs of P1-068767_D102V, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_D102V.IgG1.3, respectively; (fff) a HC comprising the HC CDRs of the HC of P1-068767_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E55A, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E55A.IgG1.3, respectively; (ggg) a HC comprising the HC CDRs of the HC of P1-068767_E30D_D52N.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E30D_D52N, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E30D_D52N.IgG1.3, respectively; (hhh) a HC comprising the HC CDRs of the HC of P1-068767_E30D_D102V.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E30D_D102V, and a HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E30D_D102V.IgG1.3, respectively; (iii) HC and LC amino acid sequences that are 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% identical to a HC comprising the HC CDRs of the HC of P1-068767_E30D.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E30D, and the HC and LC of P1-068767_E30D.IgG1.3, respectively; (jjj) a HC comprising the HC CDRs of the HC of P1-068767_E30D_E55A.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E30D_E55A, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E30D_E55A.IgG1.3, respectively; (kkk) a HC comprising the HC CDRs of the HC of P1-068767_E100fF_D102V.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E100fF_D102V, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_E100fF_D102V.IgG1.3, respectively; (lll) a HC comprising the HC CDRs of the HC of P1-068767_E55A_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E55A_E100fF, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068767_E55A_E100fF.IgG1.3, respectively; (mmm) a HC comprising the HC CDRs of the HC of P1-068767_D52N_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068767_D52N_E100fF, and HC and LC amino acid sequences that are 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% identical to the HC and LC of P1-068767_D52N_E100fF.IgG1.3, respectively; (nnn) a HC comprising the HC CDRs of the HC of P1-068767_E100fF.IgG1.3, and a LC comprising the LC CDRs of P1-068767_E100fF, and a HC and LC amino acid sequence that are 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% identical to the HC and LC of P1-068767_E100fF.IgG1.3, respectively; or (ooo) HC and LC amino acid sequences that are 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% identical to the HC comprising the HC CDRs of the HC of P1-068767_E30D_E100fF.IgG1.3, and the LC comprising the LC CDRs of P1-068767_E30D_E100fF, and the HC and LC of P1-068767_E30D_E100fF.IgG1.3, respectively. may also include:

[0094] In some embodiments, the anti-hVISTA Ab (a) a heavy chain consisting of the amino acid sequence of the heavy chain of P-061029.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P-061029; (b) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-061015.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-061015; (c) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068757.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068757; (d) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068759.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068759; (e) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761; (f) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068763.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068763; (g) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068765.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068765; (h) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767; (i) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068769.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068769; (j) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068771.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068771; (k) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068773.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068773; (l) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068775.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068775; (m) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069059.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069059; (n) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069061.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069061; (o) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069063.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069063; (p) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069065.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069065; (q) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069067.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069067; (r) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069069.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069069; (s) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069071.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069071; (t) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069073.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069073; (u) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069075.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069075; (v) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-069077.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-069077; (w) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068736, and a light chain consisting of the amino acid sequence of the light chain of P1-068736; (x) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068738.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068738; (y) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068740.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068740; (z) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068742.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068742; (aa) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068744.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068744; (bb) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068746.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068746; (cc) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068748.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068748; (dd) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068750.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068750; (ee) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068752.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068752; (ff) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068754, and a light chain consisting of the amino acid sequence of the light chain of P1-068754; (gg) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A; (hh) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_H100G.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G; (ii) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N; (jj) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A_E56N.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E56N; (kk) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D; (ll) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E55A.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E55A; (mm) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N_H100G.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_H100G; (nn) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_H100G.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_H100G; (oo) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E56N.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E56N; (pp) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E100fF, (qq) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E100fF; (rr) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_H100G_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G_E100fF; (ss) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E100fF; (tt) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_E100fF; (uu) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y; (vv) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_E55A.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E55A; a heavy chain consisting of the amino acid sequence of the heavy chain of (ww)P1-068761_E32Y_E56N.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E56N; (xx) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E32Y.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E32Y; (yy) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_H100G.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_H100G; (zz) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E100fF; a heavy chain consisting of the amino acid sequence of the heavy chain of (aaa)P1-068767_D52N_D102V.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_D102V; (bbb) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N; (ccc) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N_E55A.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E55A; (ddd) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A_D102V.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A_D102V, (eee) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D102V.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D102V; (fff) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A; (ggg) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_D52N.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D52N; (hhh) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_D102V.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D102V, (iii) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D; (jjj) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_E55A.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_E55A; (kkk) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E100fF_D102V.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E100fF_D102V, (lll) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A_E100fF; (mmm) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E100fF; (nnn) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E100fF, or (ooo) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_E100fF.IgG1.3, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_E100fF. may also include:

[0095] In some embodiments, the present disclosure provides: a heavy chain consisting of the heavy chain amino acid sequence of (a) to (ooo) listed above, followed by a Lys residue; and a light chain consisting of the light chain amino acid sequences (a) to (ooo) listed above, Anti-VISTA mAbs are contemplated in which the heavy and light chain amino acid sequences are selected from the same antibody species within (a) through (ooo) listed above.

[0096] In some embodiments, an anti-hVISTA Ab may comprise a heavy chain amino acid sequence comprising the VH amino acid sequence of an antibody species herein, but rather than the IgG1.3 heavy chain constant region as provided in the HC sequence of the Sequence Listing herein (and see SEQ ID NO: 163), the antibody may comprise a different heavy chain constant region sequence, such as a human wild-type IgG1 constant region, such as human IgG1 allotype f (IgG1f) (SEQ ID NO: 182), or a modified human IgG1 constant region, such as IgG1.1f (SEQ ID NO: 183), or a modified human IgG1 constant region, such as IgG1.P238K (SEQ ID NO: 184). Thus, embodiments of the present disclosure include: (a) a heavy chain comprising (i) the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain comprising the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068757; (d) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068759; (e) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761; (f) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068763; (g) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068765; (h) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767; (i) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068769; (j) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068771; (k) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068773; (l) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068775; (m) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069059; (n) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069061; (o) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069063; (p) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069065; (q) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069067; (r) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069069; (s) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069071; (t) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069073; (u) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069075; (v) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-069077; (w) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068736; (x) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068738; (y) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068740; (z) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068742; (aa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068744; (bb) a heavy chain comprising the amino acid sequence of P1-068746 and (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068746; (cc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068748; (dd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068750; (ee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068752; (ff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068754; (gg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A; (hh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G; (ii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N; (jj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E56N; (kk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D; (ll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E55A; (mm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_H100G; (nn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_H100G; (oo) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E56N; (pp) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E100fF; (qq) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E100fF; (rr) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G_E100fF; (ss) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E100fF; (tt) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_E100fF; (uu) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y; (vv) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E55A; (ww) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E56N; (xx) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E32Y; (yy) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_H100G; (zz) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E100fF; (aaa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_D102V; (bbb) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N; (ccc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E55A; (ddd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_D102V; (eee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_D102V; (fff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A; (ggg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D52N; (hhh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D102V; (iii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D; (jjj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E55A; (kkk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF_D102V; (lll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_E100fF; (mmm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E100fF; (nnn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF, or (ooo) (i) a heavy chain comprising the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E100fF and anti-VISTA Abs including:

[0097] Certain embodiments of the present disclosure include: (a) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068757; (d) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068759; (e) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761; (f) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068763; (g) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068765; (h) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767; (i) a heavy chain consisting of (i) the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068769; (j) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068771; (k) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068773; (l) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068775; (m) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069059; (n) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069061; (o) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069063; (p) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069065; (q) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069067; (r) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069069; (s) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069071; (t) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069073; (u) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069075; (v) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-069077; (w) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068736; (x) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068738; (y) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068740; (z) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068742; (aa) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068744; (bb) a heavy chain consisting of the amino acid sequence of P1-068746 and (ii) an amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068746; (cc) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068748; (dd) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068750; (ee) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068752; (ff) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068754; (gg) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A; (hh) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_H100G; (ii) a heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N; (jj) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A_E56N; (kk) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D; (ll) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E55A; (mm) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N_H100G; (nn) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_H100G; (oo) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E56N; (pp) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E100fF; (qq) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A_E100fF; (rr) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_H100G_E100fF; (ss) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E100fF; (tt) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N_E100fF; (uu) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y; (vv) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E55A; (ww) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E56N; (xx) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E32Y; (yy) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_H100G; (zz) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E100fF; (aaa) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_D102V; (bbb) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N; (ccc) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_E55A; (ddd) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A_D102V; (eee) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D102V; (fff) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A; (ggg) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_D52N; (hhh) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_D102V; (iii) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D; (jjj) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_E55A; (kkk) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E100fF_D102V; (lll) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A_E100fF; (mmm) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_E100fF; (nnn) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E100fF; or (ooo) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_E100fF an anti-VISTA Ab comprising: and an anti-VISTA Ab in which the C-terminal amino acid of VH and the N-terminal amino acid of SEQ ID NO: 182 form a peptide bond.

[0098] In some embodiments, the present disclosure provides: (i) a heavy chain consisting of the amino acid sequence of a VH of any one of (a) to (ooo) listed above, (ii) SEQ ID NO: 182, and (iii) a Lys residue, wherein the C-terminal amino acid of the VH and the N-terminal amino acid of SEQ ID NO: 182 form a peptide bond, and the C-terminal amino acid of SEQ ID NO: 182 is joined to the N-terminus of the Lys; and A light chain consisting of the light chain amino acid sequences (a) to (ooo) listed above. 1. An anti-VISTA mAb comprising: Anti-VISTA mAbs are contemplated in which the VH and light chain amino acid sequences are selected from the same antibody species within (a) through (ooo) listed above.

[0099] Certain embodiments of the present disclosure include: (a) a heavy chain comprising (i) the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain comprising the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068757; (d) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068759; (e) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761; (f) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068763; (g) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068765; (h) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767; (i) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068769; (j) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068771; (k) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068773; (l) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068775; (m) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069059; (n) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069061; (o) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069063; (p) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069065; (q) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069067; (r) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069069; (s) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069071; (t) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069073; (u) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069075; (v) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-069077; (w) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068736; (x) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068738; (y) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068740; (z) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068742; (aa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068744; (bb) a heavy chain comprising the amino acid sequence of P1-068746 and (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the light chain amino acid sequence of P1-068746; (cc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068748; (dd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068750; (ee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068752; (ff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068754; (gg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A; (hh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G; (ii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N; (jj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E56N; (kk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D; (ll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E55A; (mm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_H100G; (nn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_H100G; (oo) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E56N; (pp) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E100fF; (qq) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E100fF; (rr) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G_E100fF; (ss) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E100fF; (tt) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_E100fF; (uu) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y; (vv) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E55A; (ww) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E56N; (xx) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E32Y; (yy) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_H100G; (zz) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E100fF; (aaa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_D102V; (bbb) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N; (ccc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E55A; (ddd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_D102V; (eee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D102V; (fff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A; (ggg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D52N; (hhh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D102V; (iii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D; (jjj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E55A; (kkk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF_D102V; (lll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_E100fF; (mmm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E100fF; (nnn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF; or (ooo) (i) a heavy chain comprising the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E100fF. and anti-VISTA Abs including:

[0100] Certain embodiments of the present disclosure include: (a) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068757; (d) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068759; (e) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761; (f) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068763; (g) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068765; (h) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767; (i) a heavy chain consisting of (i) the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068769; (j) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068771; (k) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068773; (l) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068775; (m) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069059; (n) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069061; (o) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069063; (p) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069065; (q) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069067; (r) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069069; (s) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069071; (t) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069073; (u) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069075; (v) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-069077; (w) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068736; (x) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068738; (y) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068740; (z) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068742; (aa) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068744; (bb) a heavy chain consisting of the amino acid sequence of P1-068746 and (ii) an amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068746; (cc) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068748; (dd) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068750; (ee) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068752; (ff) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068754; (gg) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A; (hh) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_H100G; (ii) a heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N; (jj) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A_E56N; (kk) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D; (ll) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E55A; (mm) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N_H100G; (nn) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_H100G; (oo) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E56N; (pp) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E100fF; (qq) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E55A_E100fF; (rr) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_H100G_E100fF; (ss) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E100fF; (tt) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E56N_E100fF; (uu) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y; (vv) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E55A; (ww) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E56N; (xx) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E30D_E32Y; (yy) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_H100G; (zz) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068761_E32Y_E100fF; (aaa) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_D102V; (bbb) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N; (ccc) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_E55A; (ddd) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A_D102V; (eee) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_D102V; (fff) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A; (ggg) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_D52N; (hhh) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_D102V; (iii) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D; (jjj) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_E55A; (kkk) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E100fF_D102V; (lll) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E55A_E100fF; (mmm) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_D52N_E100fF; (nnn) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E100fF, or (ooo) (i) a heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068767_E30D_E100fF an anti-VISTA Ab comprising: and anti-VISTA Abs in which the C-terminal amino acid of VH and the N-terminal amino acid of SEQ ID NO: 183 form a peptide bond.

[0101] In some embodiments, the present disclosure provides: (i) a heavy chain consisting of the amino acid sequence of a VH of any one of (a) to (ooo) listed above, (ii) SEQ ID NO: 183, and (iii) a Lys residue, wherein the C-terminal amino acid of the VH and the N-terminal amino acid of SEQ ID NO: 183 form a peptide bond, and the C-terminal amino acid of SEQ ID NO: 183 is joined to the N-terminus of the Lys; and A light chain consisting of the light chain amino acid sequences (a) to (ooo) listed above. 1. An anti-VISTA mAb comprising: Anti-VISTA mAbs are contemplated in which the VH and light chain amino acid sequences are selected from the same antibody species within (a) through (ooo) listed above.

[0102] Further embodiments of the present disclosure include: (a) a heavy chain comprising (i) the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain comprising the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068757; (d) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068759; (e) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761; (f) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068763; (g) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068765; (h) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767; (i) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068769; (j) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068771; (k) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068773; (l) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068775; (m) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069059; (n) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069061; (o) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069063; (p) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069065; (q) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069067; (r) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069069; (s) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069071; (t) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069073; (u) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069075; (v) (i) a heavy chain comprising the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-069077; (w) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068736; (x) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068738; (y) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068740; (z) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068742; (aa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068744; (bb) a heavy chain comprising the amino acid sequence of P1-068746 and (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068746; (cc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068748; (dd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068750; (ee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068752; (ff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068754; (gg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A; (hh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G; (ii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N; (jj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E56N; (kk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D; (ll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E55A; (mm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_H100G; (nn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_H100G; (oo) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E56N; (pp) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E100fF; (qq) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E55A_E100fF; (rr) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_H100G_E100fF; (ss) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E100fF; (tt) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E56N_E100fF; (uu) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y; (vv) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E55A; (ww) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E56N; (xx) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E30D_E32Y; (yy) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_H100G; (zz) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E100fF; (aaa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_D102V; (bbb) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N; (ccc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E55A; (ddd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_D102V; (eee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_D102V; (fff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A; (ggg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D52N; (hhh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_D102V; (iii) a heavy chain comprising (i) the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D; (jjj) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E55A; (kkk) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF_D102V; (lll) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E55A_E100fF; (mmm) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_E100fF; (nnn) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E100fF, or (ooo) (i) a heavy chain comprising the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprising the light chain amino acid sequence of P1-068767_E30D_E100fF and anti-VISTA Abs including:

[0103] Yet further embodiments of the present disclosure include: (a) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain consisting of the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70); (b) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain consisting of the light chain amino acid sequence of P1-061015; (c) (i) a heavy chain consisting of the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 184, and a l...

Claims

1. An isolated antibody that specifically binds to hVISTA under acidic conditions.

2. The isolated antibody of claim 1, which specifically binds to hVISTA under acidic conditions but does not significantly bind under neutral or physiological conditions.

3. In acidic conditions, its K is higher than that in neutral or physiological conditions. Ｄ K less than 1 / 10 of Ｄ 3. The isolated antibody of claim 1 or 2, which binds to hVISTA at

4. In acidic conditions, its K is higher than that in neutral or physiological conditions. Ｄ K less than 1 / 100 of Ｄ 4. The isolated antibody of claim 1, which binds to hVISTA at

5. In acidic conditions, its K is higher than that in neutral or physiological conditions. Ｄ K less than 1 / 1000 of Ｄ 5. The isolated antibody of claim 1, which binds to hVISTA at

6. Under neutral or physiological conditions, 10 －５ M or a larger K Ｄ 6. The isolated antibody of claim 1, wherein the antibody binds to hVISTA at

7. Under neutral or physiological conditions, 10 －４ M or a larger K Ｄ 7. The isolated antibody of claim 1, which binds to hVISTA at

8. Under neutral or physiological conditions, 10 －３ M or a larger K Ｄ 8. The isolated antibody of claim 1, which binds to hVISTA at

9. Under acidic conditions, 10 －７ M or smaller K Ｄ 9. The isolated antibody of claim 1, which binds to hVISTA at

10. Under acidic conditions, 10 －８ M or smaller K Ｄ 10. The isolated antibody of claim 1, which binds to hVISTA at

11. Under acidic conditions, 10 －９ M or smaller K Ｄ 11. The isolated antibody of any one of claims 1 to 10, which binds to hVISTA at

12. Under acidic conditions, 10 －７ Or a smaller K Ｄ and binds to hVISTA at 10 －４ or a larger K Ｄ 12. The isolated antibody of claim 1, which binds to hVISTA at

13. Under acidic conditions, 10 －７ Or a smaller K Ｄ and binds to hVISTA at 10 －５ or a larger K Ｄ 13. The isolated antibody of any one of claims 1 to 12, which binds to hVISTA at

14. In acidic conditions, its k is lower than that in neutral or physiological conditions. ｏｆｆ k less than one fifth of ｏｆｆ 14. The isolated antibody of any one of claims 1 to 13, which binds to hVISTA at

15. In acidic conditions, its k is lower than that in neutral or physiological conditions. ｏｆｆ k less than 1 / 10 of ｏｆｆ 15. The isolated antibody of any one of claims 1 to 14, which binds to hVISTA at

16. In acidic conditions, its k is lower than that in neutral or physiological conditions. ｏｆｆ k less than 1 / 50 of ｏｆｆ 16. The isolated antibody of any one of claims 1 to 15, which binds to hVISTA at

17. In acidic conditions, its k is lower than that in neutral or physiological conditions. ｏｆｆ k less than 1 / 100 of ｏｆｆ 17. The isolated antibody of any one of claims 1 to 16, which binds to hVISTA at

18. In acidic conditions, 7 × 10 －３ s －１ Or a smaller k ｏｆｆ 18. The isolated antibody of any one of claims 1 to 17, which binds to hVISTA at

19. In acidic conditions, 5 × 10 －３ s －１ Or a smaller k ｏｆｆ 19. The isolated antibody of any one of claims 1 to 18, which binds to hVISTA at

20. In acidic conditions, 3 × 10 －３ s －１ Or a smaller k ｏｆｆ 20. The isolated antibody of any one of claims 1 to 19, which binds to hVISTA at

21. Under acidic conditions, 10 －３ s －１ Or a smaller k ｏｆｆ 21. The isolated antibody of any one of claims 1 to 20, which binds to hVISTA at

22. In acidic conditions, 7 × 10 －４ s －１ Or a smaller k ｏｆｆ 22. The isolated antibody of any one of claims 1 to 21, which binds to hVISTA at

23. In acidic conditions, 5 × 10 －４ s －１ Or a smaller k ｏｆｆ 23. The isolated antibody of any one of claims 1 to 22, which binds to hVISTA at

24. In acidic conditions, 3 × 10 －４ s －１ Or a smaller k ｏｆｆ 24. The isolated antibody of any one of claims 1 to 23, which binds to hVISTA at

25. Under acidic conditions, 10 －４ s －１ Or a smaller k ｏｆｆ 25. The isolated antibody of any one of claims 1 to 24, which binds to hVISTA at

26. In acidic conditions, 7 × 10 －５ s －１ Or a smaller k ｏｆｆ 26. The isolated antibody of any one of claims 1 to 25, which binds to hVISTA at

27. In acidic conditions, 5 × 10 －５ s －１ Or a smaller k ｏｆｆ 27. The isolated antibody of any one of claims 1 to 26, which binds to hVISTA at

28. In acidic conditions, 3 × 10 －５ s －１ Or a smaller k ｏｆｆ 22. The isolated antibody of any one of claims 1 to 21, which binds to hVISTA at

29. Under acidic conditions, 10 －５ s －１ Or a smaller k ｏｆｆ 29. The isolated antibody of any one of claims 1 to 28, which binds to hVISTA at

30. Under neutral or physiological conditions, 10 －３ s －１ or a larger k ｏｆｆ 30. The isolated antibody of any one of claims 1 to 29, which binds to hVISTA at

31. In neutral or physiological conditions, 3 × 10 －３ s －１ or a larger k ｏｆｆ 31. The isolated antibody of any one of claims 1 to 30, which binds to hVISTA at

32. In neutral or physiological conditions, 5 × 10 －３ s －１ or a larger k ｏｆｆ 32. The isolated antibody of any one of claims 1 to 31, which binds to hVISTA at

33. In neutral or physiological conditions, 7 × 10 －３ s －１ or a larger k ｏｆｆ 33. The isolated antibody of any one of claims 1 to 32, which binds to hVISTA at

34. Under neutral or physiological conditions, 10 －２ s －１ or a larger k ｏｆｆ 34. The isolated antibody of any one of claims 1 to 33, which binds to hVISTA at

35. In neutral or physiological conditions, 3 × 10 －２ s －１ or a larger k ｏｆｆ 35. The isolated antibody of any one of claims 1 to 34, which binds to hVISTA at

36. In neutral or physiological conditions, 5 × 10 －２ s －１ or a larger k ｏｆｆ 36. The isolated antibody of any one of claims 1 to 35, which binds to hVISTA at

37. In neutral or physiological conditions, 7 × 10 －２ s －１ or a larger k ｏｆｆ 37. The isolated antibody of any one of claims 1 to 36, which binds to hVISTA at

38. 38. The isolated antibody of any one of claims 1 to 37, wherein binding of the antibody to hVISTA under neutral or physiological conditions is not detectable, for example by SPR.

39. In acidic conditions, 5 × 10 －３ s －１ Or a smaller k ｏｆｆ and in neutral or physiological conditions, 7 × 10 －３ s －１ or a larger k ｏｆｆ 39. The isolated antibody of any one of claims 1 to 38, which binds to hVISTA at

40. Under acidic conditions, 10 －４ s －１ Or a smaller k ｏｆｆ and under neutral or physiological conditions, 10 －２ s －１ or a larger k ｏｆｆ 40. The isolated antibody of any one of claims 1 to 39, which binds to hVISTA at

41. Under acidic conditions, 10 －８ M or smaller K Ｄ and 5 x 10 －３ s －１ Or a smaller k ｏｆｆ At neutral physiological conditions, －６ M or a larger K Ｄ and 7 x 10 －３ s －１ or a larger k ｏｆｆ 41. The isolated antibody of any one of claims 1 to 40, which binds to hVISTA at

42. Under acidic conditions, 10 －８ M or smaller K Ｄ and 3 x 10 －３ s －１ Or a smaller k ｏｆｆ At neutral physiological conditions, －６ M or a larger K Ｄ and 10 －２ s －１ or a larger k ｏｆｆ 42. The isolated antibody of any one of claims 1 to 41, which binds to hVISTA at

43. Under acidic conditions, 10 －１２ ~10 －８ K of M Ｄ and 10 －４ ~5×10 －３ s －１ No. ｏｆｆ At neutral physiological conditions, －７ ~10 －４ K of M Ｄ and 3 x 10 －３ ~10 －２ s －１ or a larger k ｏｆｆ 43. The isolated antibody of any one of claims 1 to 42, which binds to hVISTA at

44. Under acidic conditions, 10 －１２ ~10 －８ K of M Ｄ and 10 －４ ~5×10 －３ s －１ No. ｏｆｆ At neutral physiological conditions, －７ ~10 －４ K of M Ｄ and 3 x 10 －３ ~10 －２ s －１ or a larger k ｏｆｆ Binds to hVISTA at 10 －７ Or a smaller K Ｄ 44. The isolated antibody of any one of claims 1 to 43, which binds to cyno VISTA at .

45. At pH 6.9, the K is 10 times lower than at pH 7.

4. Ｄ and / or at pH 6.5, a K that is 100 times lower than at pH 7.4 Ｄ At pH 6.0, the K is 1000 times lower than at pH 7.

4. Ｄ 45. The isolated antibody of any one of claims 1 to 44, which binds to hVISTA at

46. 46. ​​The isolated antibody of any one of claims 1 to 45, which binds to cyno VISTA.

47. 47. The isolated antibody of claim 46, which binds to cyno VISTA with higher affinity under acidic conditions compared to physiological conditions.

48. Under acidic conditions, 10 －８ Or a smaller K Ｄ and / or 10 －２ Or a smaller k ｏｆｆ and under physiological conditions, 10 －６ or a larger K Ｄ and / or 10 －２ or a larger k ｏｆｆ 48. The isolated antibody of any one of claims 45 to 47, which binds to cyno VISTA at

49. The isolated antibody of any one of claims 1 to 48, wherein the acidic conditions are conditions having a pH of 6.5 or lower.

50. 50. The isolated antibody of any one of claims 1 to 49, wherein the acidic conditions are conditions having a pH of 6.0 to 6.

5.

51. The isolated antibody of any one of claims 1 to 50, wherein the neutral conditions are conditions having a pH of 7.

0.

52. 52. The isolated antibody of any one of claims 1 to 51, wherein the physiological conditions are conditions having a pH of 7.35 to 7.

45.

53. 53. The isolated antibody of any one of claims 1 to 52, wherein the physiological conditions are conditions having a pH of 7.

4.

54. 54. The isolated antibody of any one of claims 1 to 53, which inhibits binding of hVISTA to human T cells, such as human CD4+ T cells (is an antagonist antibody).

55. 55. The isolated antibody of claim 54, which inhibits binding of hVISTA to human T cells under conditions having a pH of less than pH 7.

0.

56. 56. The isolated antibody of any one of claims 1 to 55, which inhibits binding of hVISTA to huPSGL-1.

57. 57. The isolated antibody of claim 56, which inhibits binding of hVISTA to huPSGL-1 under conditions having a pH of less than pH 7.

0.

58. 58. The isolated antibody of any one of claims 1 to 57, which inhibits binding of hVISTA to heparan sulfate proteoglycans.

59. 59. The isolated antibody of claim 58, which inhibits binding of hVISTA to heparan sulfate proteoglycans under conditions having a pH of less than pH 7.

0.

60. 60. The isolated antibody of any one of claims 55, 57, or 59, wherein the condition having a pH of less than pH 7.0 is a tumor or any disease area of ​​a subject having a pH of less than pH 7.0 and where immune stimulation is desired.

61. 61. The isolated antibody of any one of claims 1 to 60, which stimulates T cell activation.

62. 62. The isolated antibody of claim 61, which stimulates human T cell activation under conditions having a pH of less than pH 7.

0.

63. 63. The isolated antibody of any one of claims 1 to 62, which reduces VISTA-mediated cell-cell adhesion.

64. 54. The isolated antibody of any one of claims 1 to 53, which stimulates activation of VISTA (is an agonistic antibody).

65. 65. The isolated antibody of any one of claims 1-53 and 64, which stimulates binding of hVISTA to human T cells, such as human CD4+ T cells.

66. 66. The isolated antibody of claim 65, which stimulates binding of hVISTA to human T cells under conditions having a pH of less than pH 7.

0.

67. 67. The isolated antibody of any one of claims 1-53 and 64-66, which stimulates binding of hVISTA to huPSGL-1.

68. 68. The isolated antibody of claim 67, which stimulates binding of hVISTA to huPSGL-1 under conditions having a pH of less than pH 7.

0.

69. 70. The isolated antibody of any one of claims 1-53 and 64-68, which stimulates binding of hVISTA to heparan sulfate proteoglycans.

70. 70. The isolated antibody of claim 69, which stimulates binding of hVISTA to heparan sulfate proteoglycans under conditions having a pH of less than pH 7.

0.

71. 71. The isolated antibody of any one of claims 66, 68, or 70, wherein the condition having a pH of less than pH 7.0 is an autoimmune (e.g., rheumatoid arthritis and lupus) environment, an inflammatory site, or any disease area in a subject having a pH of less than pH 7.0 where immune inhibition is desired.

72. 72. The isolated antibody of any one of claims 1-71, having a mean residence time in cynomolgus monkeys of at least 500 days.

73. 73. The isolated antibody of any one of claims 1 to 72, which does not significantly bind to VISTA positive cells, such as neutrophils, in the peripheral blood of a subject to which it is administered.

74. 74. The isolated antibody of any one of claims 1 to 73, which does not significantly deplete VISTA positive cells, such as neutrophils, in the peripheral blood of a subject to which it is administered.

75. 75. The antibody of any one of claims 1 to 74, which is engineered to bind to hVISTA at acidic pH but not at neutral or physiological pH.

76. 76. The antibody of claim 75, wherein one to eight amino acids of VH CDR1, CDR2, and / or CDR3 have been engineered by replacing them with glutamic acid, aspartic acid, or histidine residues.

77. The antibody of any one of claims 1-63 and 72-76, comprising the VH CDR1, CDR2, and / or CDR3 of P1-061029, or a variant thereof comprising 1-6 or 1-8 amino acid differences in CDR1, CDR2, and / or CDR3 compared to P1-061029, wherein a maximum of 1, 2, or 3 amino acid mutations are present in any one CDR.

78. 78. The antibody of claim 77, comprising the VH CDR1, CDR2, and CDR3 of P1-061029, or a variant thereof comprising 1-6 or 1-8 amino acid differences in CDR1, CDR2, and / or CDR3 compared to P1-061029.

79. The antibody of claim 77 or 78, wherein the amino acid mutation is a substitution with a glutamic acid residue (E), an aspartic acid residue (D), or a histidine residue (H).

80. - GFTX １ X ２ D.X. ３ AMH, wherein X １ is D or L, and X ２ is E or D, and X ３ CDR1 (SEQ ID NO:463) is E or Y; - GIX ４ WX ５ S.X. ６ X ７ IGYADSVKG, wherein X ４ is D or N, and X ５ is D or N, and X ６ is D, E, H, or A, and X ７ is D, E, H, or N; and / or - VPGYSX ８ GWIDAX ９ D.X. １０ wherein X ８ is E, H, or G, and X ９ is E, D, or F, and X １０ CDR3 (SEQ ID NO: 465) is D, E, or V The antibody of any one of claims 77 to 79, comprising:

81. - GFTX １ X ２ D.X. ３ AMH, wherein X １ is D or L, and X ２ is E or D, and X ３ CDR1 (SEQ ID NO:463) is E or Y; - GIX ４ WX ５ S.X. ６ X ７ IGYADSVKG, wherein X ４ is D or N, and X ５ is D or N, and X ６ is D, E, H, or A, and X ７ is D, E, H, or N; and - VPGYSX ８ GWIDAX ９ D.X. １０ wherein X ８ is E, H, or G, and X ９ is E, D, or F, and X １０ CDR3 (SEQ ID NO: 465) is D, E, or V The antibody of claim 80, comprising:

82. X ３ is E and X ９ The antibody of claim 80 or 81, wherein is E.

83. X ２ is E and X ７ is E, and / or X ８ The antibody of any one of claims 80 to 82, wherein is H.

84. X ２ is E and X ７ is E, and X ８ The antibody of claim 83, wherein two or more of the following are satisfied:

85. X ２ is E and X ７ is E, and X ８ The antibody of claim 84, wherein is H.

86. X ６ The antibody of any one of claims 80 to 85, wherein is E.

87. X ６ The antibody of any one of claims 80 to 85, wherein is A.

88. X １ is L, and X ４ is N, and X ５ is N, and / or X １０ The antibody of any one of claims 80 to 86, wherein is V.

89. X １ is L, X ４ is N, X ５ is N, and / or X １０ The antibody of claim 88, wherein two or more of:

90. X １ is L, X ４ is N, X ５ is N, and / or X １０ The antibody of claim 89, wherein three or more of the following are satisfied:

91. X １ is L, and X ４ is N, and X ５ is N, and / or X １０ The antibody of claim 90, wherein is V.

92. X １０ The antibody of any one of claims 80 to 91, wherein is D.

93. X ９ The antibody of any one of claims 80 to 92, wherein is E.

94. X ２ is E and X ４ is D, and / or X ６ The antibody of any one of claims 80 to 93, wherein is E.

95. X ２ is E, X ４ is D, and / or X ６ The antibody of claim 94, wherein two or more of the following are satisfied:

96. X ２ is E and X ４ is D, and X ６ The antibody of claim 95, wherein is E.

97. X １ is L, X3 is Y, and X ５ is N, and X ７ is N, and / or X ８ The antibody of any one of claims 80 to 96, wherein is G.

98. X １ is L, X3 is Y, X ５ is N, X ７ is N, and / or X ８ The antibody of claim 97, wherein two or more of the following are satisfied:

99. X １ is L, X3 is Y, X ５ is N, X ７ is N, and / or X ８ The antibody of claim 98, wherein three or more of the following are satisfied:

100. X １ is L, X3 is Y, X ５ is N, X ７ is N, and / or X ８ The antibody of claim 99, wherein four or more of the following are satisfied:

101. X １ is L, X3 is Y, and X ５ is N, and X ７ is N, and X ８ The antibody of claim 100, wherein is G.

102. The antibodies are P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-06877 5, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-068761_E 55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, or P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-06876 1_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, or P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E5 VH of 5A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF An antibody according to any one of claims 77 to 101, comprising CDR1, CDR2 and / or CDR3.

103. P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1- 069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-069077, P1-068 761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, or P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-0 68761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32 Y. VH of 5A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF The antibody of claim 102, comprising CDR1, CDR2, and CDR3.

104. The antibody of any one of claims 77 to 103, comprising the VL CDR1, CDR2, and CDR3 of P1-061029.

105. P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P 1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1- 069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-069077, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, or P1- 068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068 761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P 1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-0687 61_E30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068 767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E5 5A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1 105. The antibody of any one of claims 1 to 63 and 72 to 104, comprising a VH comprising an amino acid sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to the amino acid sequence of -068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF.

106. P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765 , P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059 , P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-06907 1, P1-069073, P1-069075, P1-069077, P1-069077, P1-068761_E55A, P1- 068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, or P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068 761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, or P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-06876 7_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF.

107. The antibody of any one of claims 1 to 106, comprising a VL comprising an amino acid sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to the amino acid sequence of P1-061029.

108. The antibody described in claim 107, comprising the VL of P1-061029.

109. The antibody of any one of claims 1-63 and 72-76, comprising the VH CDR1, CDR2, and / or CDR3 of P1-061015, or a variant thereof comprising 1-6 or 1-8 amino acid differences in CDR1, CDR2, and / or CDR3 compared to P1-061015, wherein a maximum of 1, 2, or 3 amino acid mutations are present in any one CDR.

110. The antibody of claim 109, comprising VH CDR1, CDR2, and CDR3 of P1-061015, or a variant thereof comprising 1 to 6 amino acid differences in CDR1, CDR2, and / or CDR3 compared to P1-061015, wherein a maximum of 1, 2, or 3 amino acid mutations are present in any one CDR.

111. The antibody of claim 108 or 109, wherein the amino acid mutation is a substitution with a glutamic acid residue (E), an aspartic acid residue (D), or a histidine residue (H).

112. - GFTFX １ X ２ X ３ MH, wherein X １ is E, D, H, or S, and X ２ is H or Y, and X ３ CDR1 (SEQ ID NO: 466) is D or A; -X ４ X ５ WX ６ DGSX ７ X ８ X ９ X １０ ADSVKG, wherein X ４ is E, H, or I, and X ５ is D or I, and X ６ is D or Y, and X ７ is D or N, and X ８ is D, H, or K, and X ９ is D, H, or Y, and X １０ is E or Y; and / or -DX １１ X １２ FYX １３ X １４ YYDFX １５ wherein X １１ is E or S, and X １２ is E or G, and X １３ is D, E, or S, and X １４ is D or S, and X １５ CDR3 (SEQ ID NO: 468) is D, E, or Y The antibody of any one of claims 108 to 111, comprising:

113. - GFTFX １ X ２ X ３ MH, wherein X １ is E, D, H, or S, and X ２ is H or Y, and X ３ CDR1 (SEQ ID NO: 466) is D or A; -X ４ X ５ WX ６ DGSX ７ X ８ X ９ X １０ ADSVKG, wherein X ４ is E, H, or I, and X ５ is D or I, and X ６ is D or Y, and X ７ is D or N, and X ８ is D, H, or K, and X ９ is D, H, or Y, and X １０ is E or Y; and -DX １１ X １２ FYX １３ X １４ YYDFX １５ wherein X １１ is E or S, and X １２ is E or G, and X １３ is D, E, or S, and X １４ is D or S, and X １５ CDR3 (SEQ ID NO: 468) is D, E, or Y The antibody of any one of claims 108 to 112, comprising:

114. 103. The antibody of any one of claims 98-102, comprising the VH CDR1, CDR2, and / or CDR3 of P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068748, P1-068750, P1-068752, or P1-068754.

115. The antibody of claim 114, comprising the VH CDR1, CDR2, and CDR3 of P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068748, P1-068750, P1-068752, or P1-068754.

116. The antibody of any one of claims 98 to 115, comprising the VL CDR1, CDR2, and CDR3 of P1-061015.

117. 117. The antibody of any one of claims 98 to 116, comprising a VH comprising an amino acid sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to the amino acid sequence of P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068748, P1-068750, P1-068752, or P1-068754.

118. The antibody of any one of claims 98 to 117, comprising a VH comprising the amino acid sequence of the VH of P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068748, P1-068750, P1-068752, or P1-068754.

119. The antibody of any one of claims 98 to 118, comprising a VL comprising an amino acid sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to the amino acid sequence of P1-061015.

120. The antibody of claim 119, comprising a VL comprising the amino acid sequence of P1-061015.

121. 121. The isolated antibody of any one of claims 1 to 120, which binds to or near the histidine-rich region of hVISTA.

122. 122. The isolated antibody of claim 121, which binds to or near the histidine-rich region of hVISTA under conditions having a pH of 6.0 to 6.

5.

123. Regarding binding to hVISTA, P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1 -069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-069077, P1-068761_E55A, P1-068761_H100G, P 1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G,P1-068761_E30D_H100G, or P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_ E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1 -068767_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V , P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55 A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, P1-0 The isolated antibody of any one of claims 1 to 122, which competes or cross-competes with one or more antibodies comprising the VH and VL of 68767_E30D_E100fF, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068748, P1-068750, P1-068752 or P1-068754.

124. The antibody of any one of claims 1 to 123, which does not significantly bind to hVISTA wherein one or more of the following amino acid residues have been mutated: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127.

125. An antibody that binds to hVISTA consisting of SEQ ID NO: 1 or 2, but does not significantly bind to hVISTA in which one or more of the following amino acid residues have been mutated: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127.

126. The antibody of any one of claims 1 to 125, which does not significantly bind to hVISTA mutated at two, three, four, five or more of the following amino acid residues: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127.

127. The antibody of any one of claims 124-126, which does not bind to hVISTA in which one or more of the following residues have been mutated to one of the corresponding residues shown in Table 15:

128. For example, the isolated antibody of any one of claims 1 to 127 has an isoelectric point (pI) of 6.5 to 6.8, as measured by icIEF.

129. 129. The isolated antibody of any one of claims 1-128, which exhibits low aggregation, e.g., similar to or less aggregation than '029, '761, or '767, as determined in the Examples.

130. 130. The isolated antibody of any one of claims 1-129, which exhibits a viscosity similar to or lower than that of '029, '761, or '767, eg, as determined in the Examples.

131. The isolated antibody of any one of claims 1-130, which exhibits a hydrodynamic radius similar to or lower than the hydrodynamic radius of '029, '761, or '767, e.g., as determined in the Examples.

132. 132. The isolated antibody of any one of claims 1-131, which exhibits a Tm1 similar to or higher than that of '029, '761, or '767, eg, as determined in the Examples.

133. The isolated antibody of any one of claims 1-132, which exhibits an amount of high molecular weight species that is similar to or lower than the amount of high molecular weight species of '029, '761, or '767, e.g., as determined in the Examples.

134. 134. The isolated antibody of any one of claims 1 to 133, which is an IgG antibody.

135. 135. The isolated antibody of claim 134, which is an IgG1, IgG2, or IgG4 antibody (optionally IgG4 with S228P).

136. 136. The isolated antibody of any one of claims 1 to 135, which is an effectorless antibody.

137. 137. The isolated antibody of claim 136, wherein the constant region comprises one to five mutations of the wild-type heavy chain constant region that reduce an effector function of the antibody.

138. 138. The isolated antibody of any one of claims 1-137, wherein the constant region of the antibody is IgG1.3, IgG1.1, or IgG1 with a P238K substitution.

139. 136. The isolated antibody of any one of claims 1 to 135, which has an effector function.

140. 140. The isolated antibody of claim 139, which is afucosylated (e.g., an afucosylated IgG1 antibody).

141. The isolated antibody of claim 139 or 140, wherein the constant region comprises one to five mutations that enhance the effector function of the antibody.

142. 142. The isolated antibody of any one of claims 1 to 141, which is a full-length antibody.

143. 142. The isolated antibody of any one of claims 1 to 141, which is an antigen-binding fragment of an antibody.

144. 144. The isolated antibody of any one of claims 1-143, which is a multimeric (e.g., dimeric or trimeric) antibody.

145. The isolated antibody of any one of claims 1 to 144, which is linked (eg, covalently) to another molecule.

146. The isolated antibody of claim 145, wherein the other molecule is a label.

147. The isolated antibody of claim 145 or 146, wherein the other molecule is a peptide.

148. 148. The isolated antibody of any one of claims 1 to 147, which is an antibody drug conjugate (ADC).

149. An isolated nucleic acid encoding the antibody of any one of claims 1 to 148.

150. An isolated nucleic acid encoding the heavy and / or light chain of an antibody according to any one of claims 1 to 149.

151. A composition comprising a nucleic acid encoding a heavy chain of an antibody according to any one of claims 1 to 150, and a nucleic acid encoding a light chain of the antibody.

152. A cell comprising the isolated nucleic acid of any one of claims 149 to 151.

153. 153. A method for preparing an antibody, comprising culturing a cell according to claim 152 under conditions in which the antibody is expressed.

154. A composition comprising an isolated antibody, nucleic acid, composition, or cell of any one of claims 1 to 152, and a pharma- ceutically acceptable carrier.

155. The composition of claim 154, comprising a second therapeutic agent.

156. The composition of claim 155, wherein the second therapeutic agent is an immunostimulant.

157. The composition of claim 156, wherein the immunostimulatory agent is an antagonist of an immunosuppressive molecule, such as PD-1 / PD-L1, CTLA-4, and LAG-3, or an agonist of an immunostimulatory molecule, such as GITR and OX40.

158. A method for treating a subject having cancer comprising administering to the subject a therapeutically effective amount of a composition or isolated antibody of any one of claims 1-152 and 154-157 which stimulates an immune response and / or is a VISTA antagonist antibody.

159. The method of claim 158, wherein the subject has VISTA positive cells in the cancer tumor.

160. The method of claim 159, wherein the cells are VISTA-positive infiltrating lymphocytic (e.g., T cells) or myelomonocytic cells.

161. The method of any one of claims 158 to 160, wherein the subject is first tested for the presence of VISTA positive cells in the tumor.

162. 162. The method of any one of claims 158-161, further comprising administering a second therapy.

163. 163. The method of claim 162, wherein the second therapy is radiation therapy, surgery, or administration of a second agent.

164. 164. The method of claim 163, wherein the second therapy is a second agent, and the second agent is an immunostimulant.

165. The method of claim 164, wherein the immunostimulatory agent is an antagonist of an immunosuppressant molecule, such as PD-1 / PD-L1, CTLA-4, and LAG-3, or an agonist of an immunostimulatory molecule, such as GITR and OX40.

166. A method for treating an infectious disease (e.g., a viral disease) in a subject comprising administering to the subject a therapeutically effective amount of a composition or isolated antibody of any one of claims 1-152 and 154-157 that stimulates an immune response and / or is a VISTA antagonist.

167. A method for treating inflammation, inflammatory conditions, and autoimmune diseases, graft versus host disease, or diseases that would benefit from a reduced immune response comprising administering to a subject a therapeutically effective amount of a composition or isolated antibody of any one of claims 1-152 and 154-157 that inhibits an immune response, e.g., T cell activation, or is a VISTA agonist.

168. 10 at pH 6.5 or lower －７ M or smaller K Ｄ 2. A method for identifying Abs that bind to hVISTA-ECD at pH 6.5 or lower, comprising contacting a test Ab or a plurality of test Abs with a polypeptide comprising the IgV domain of hVISTA-ECD or a fragment thereof comprising amino acids 20-95, 20-70, 35-70-127, or 35-127 of SEQ ID NO:2 at pH 6.5 or lower, and contacting the polypeptide with an antibody or antibody fragment thereof comprising the IgV domain of hVISTA-ECD at pH 6.5 or lower. －７ M or smaller K Ｄ selecting a test Ab or test Abs that bind at

169. 5×10 at pH 6.5 or lower －３ sec －１ Or a smaller K ｏｆｆ 2. A method for identifying Abs that bind to hVISTA-ECD at pH 6.5 or lower, comprising contacting a test Ab or a plurality of test Abs with hVISTA-ECD or a polypeptide comprising the IgV domain of hVISTA-ECD or a fragment thereof comprising amino acids 20-95, 20-70, 35-70, or 35-127 of SEQ ID NO:2 at pH 6.5 or lower, and contacting the polypeptide with 5×10 －３ sec －１ Or a smaller K ｏｆｆ selecting a test Ab or test Abs that bind at

170. 1. A method for identifying Abs that specifically bind to hVISTA-ECD at pH 6.5 with similar affinity as at pH 7.0, comprising: a. contacting a test Ab or test Abs with hVISTA-ECD or a polypeptide comprising the IgV domain of hVISTA-ECD or a fragment thereof comprising amino acids 20-95, 20-70, or 35-70, or 35-127 of SEQ ID NO:2 at pH 6.5; b. contacting a test Ab or test Abs with the polypeptide of (a) at pH 7.0; and c. At pH 6.5 and pH 7.0, 10 －７ M or smaller K Ｄ and selecting a test Ab if it binds to the polypeptide at The method includes:

171. 1. A method for identifying Abs that bind to hVISTA-ECD with higher affinity at pH 6.5 than at pH 7.0, comprising: a. contacting a test Ab or test Abs with hVISTA-ECD or a polypeptide comprising the IgV domain of hVISTA-ECD or a fragment thereof comprising amino acids 20-95, 20-70, 35-70, or 35-127 of SEQ ID NO:2 at pH 6.5; b. contacting a test Ab or test Abs with the polypeptide of (a) at pH 7.0; and c. At pH 6.5, the K is less than half that at pH 7.0 Ｄ Or k ｏｆｆ and selecting the test Ab if it binds to the polypeptide. The method includes:

172. 1. A method for identifying Abs that specifically bind hVISTA-ECD for use in treating cancer, comprising: c. Identifying an Ab that specifically binds to hVISTA-ECD at pH 6.5 or lower, such as by the methods described in claims 168-171; and d. Selecting Abs of (a) that initiate or enhance immune responses or inhibit tumor growth in tumor models at pH 6.5 or lower. The method includes:

173. 173. The method of claim 172, wherein step (b) comprises measuring T cell activity.

174. The method of claim 172 or 173, further comprising measuring the anti-tumor effect of the Ab.

175. 1. A method for improving the anti-tumor efficacy of an Ab that binds to hVISTA-ECD, comprising: a. providing an Ab that binds to hVISTA-ECD with an affinity less than a desired value at pH 6.5 or lower; b. replacing 1-5 amino acid residues of the heavy or light chain of the Ab with different amino acid residues, wherein the 1-5 amino acid residues are contact residues with hVISTA-ECD; e. determining whether the Abs obtained in (b) have a higher affinity for hVISTA-ECD at pH 6.5 or lower than the Abs in (a); and f. At pH 6.5 or lower, 10 －７ M or smaller K Ｄ repeating steps (a)-(c) a number of rounds sufficient to obtain an Ab that binds to hVISTA-ECD. The method includes:

176. 1. A method for improving the anti-tumor efficacy of an Ab that binds to hVISTA-ECD, comprising: a. providing an Ab that binds to hVISTA-ECD with an affinity less than a desired value at pH 6.5 or lower; b. preparing a library of variants of the Ab of (a), each variant comprising substitution of 1 to 5 amino acid residues in a heavy or light chain of the Ab with a different amino acid residue, wherein the 1 to 5 amino acid residues are contact residues with hVISTA-ECD; c. At pH 6.5 or lower, －７ M or smaller K Ｄ selecting Abs from the library of mutants of (b) that bind to hVISTA-ECD at d. Testing the antitumor efficacy of the Abs of (c) in tumor models. The method includes:

177. A method for improving the pharmacokinetics of an antibody that binds to human VISTA ECD, the method comprising enhancing the ability of the antibody to bind to human VISTA under acidic conditions, e.g., pH equal to or less than 6.

5.

178. A method for selecting an antibody that binds to human VISTA and has a longer half-life (good pharmacokinetic properties), the method comprising selecting an antibody that binds to human VISTA under acidic conditions, e.g., pH equal to or lower than 6.

5.

179. A method for improving the efficacy of an antibody binding to hVISTA, comprising increasing the number of aspartic acid, glutamic acid, and / or histidine residues in one or more VH CDRs of the antibody to enhance binding of the antibody to hVISTA at acidic pH.

180. A method for isolating an antibody that binds to hVISTA, has a long half-life in human blood, and / or stimulates T cells in a tumor environment, comprising screening a library of antibodies that bind to hVISTA for those that bind at acidic pH but not at neutral pH.

181. 181. The method of any one of claims 168-180, comprising counterselecting an antibody that binds at physiological pH.

182. 182. The method of any one of claims 168-181, further comprising selecting an antibody that is either a VISTA antagonist or a VISTA agonist.

183. 183. A method according to any one of claims 168 to 182, comprising selecting an antibody which inhibits the interaction of VISTA with a VISTA co-receptor and / or the interaction of VISTA with T cells or myelomonocytic cells.

184. 184. The method of any one of claims 168-183, further comprising selecting an antibody having one or more of the characteristics of P1-068761 or P1-068767.

185. 149. A method for detecting VISTA in a sample, the method comprising contacting the sample with a VISTA antibody according to any one of claims 1 to 148.

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