Antibodies that bind to VISTA at acidic pH

Abstract

The present application relates to antibodies that specifically bind to a T cell activation inhibitor (VISTA) containing a V domain immunoglobulin at an acidic pH and its use in cancer treatment. In some embodiments, the antibody specifically binds to human VISTA at an acidic pH, but does not significantly bind to human VISTA at a neutral or physiological pH.

Description

Technical Field

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

[0002] Background and Summary of the Invention

[0003] V-domain Ig-containing inhibitor of T-cell activation, or VISTA, is a co-inhibitory member of the B7 family of immunoreceptors expressed by myelomonocytic cells and other leukocytes. However, the mechanism by which VISTA suppresses immune responses is poorly understood.

[0004] The inventors have found that, unlike other known immune receptors, VISTA can engage with its counter-receptor and selectively work at acidic pH, and has very little activity at physiological pH (e.g., 7.3-7.4). Therefore, VISTA can suppress the immune response in acidic microenvironments (such as tumor beds or inflammatory sites) without interfering with cells circulating in the blood or present in non-inflamed, non-acidic tissues. In addition, the inventors have found that anti-VISTA antibodies can be engineered to selectively bind to VISTA at acidic pH, and hardly bind at physiological pH, which reflects the acidic pH selectivity of VISTA itself. Relative to antibodies that bind VISTA at physiological pH, these acidic pH selective antibodies can provide desired properties for treating diseases (such as cancer).

[0005] 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 barely bind at neutral or physiological pH. The inventors have noted herein 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 unusually high relative to other B7 family members and other immunoglobulin superfamily members. (See Figure 1A and Figure 1B . ) In solution, the pK of the amino acid histidine aThe pH value of VISTA is about 6.5, which means that at pH 6.5 or lower, the histidine residues in the protein tend to be protonated, therefore positively charged, and at a pH higher than pH 6.5, they are increasingly non-protonated and have a neutral charge. Tumor microenvironments and inflamed tissues are typically acidic, and therefore, the VISTA proteins found in these microenvironments may be at least partially protonated at their histidine residues. As discussed herein, the inventors have hypothesized that histidine protonation may affect the conformation, surface structure and / or charge density of VISTA, which in turn may produce pH-specific or pH-selective epitopes for one or more receptor-ligand interactions and antibody binding. Targeting VISTA using antibodies bound at acidic pH rather than neutral or physiological pH can prevent target-mediated drug deposition via circulating and bone marrow mononuclear cells present in lymphoid organs, thereby improving antibody PK, receptor occupancy, and activity in the tumor microenvironment. In the context of 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), acidic pH-selective antibodies can also improve the specificity of VISTA antibodies for target cells within tumors rather than circulating target cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Color versions of some of the drawings are provided in priority U.S. Provisional Application No. 62 / 636,746, filed on February 28, 2018. Copies of the color drawings are available from the U.S. Patent and Trademark Office upon request and payment of the necessary fee.

[0007] Figures 1A to 1C We show that the extracellular domain of VISTA contains an unusually high frequency of histidine residues, many of which are conserved, and at least some of which may be involved in receptor-ligand binding. Figure 1A A graph of immunoglobulin domain-containing proteins is shown, 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 within 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 The comparison amino acid sequences of the extracellular domains of human, cynomolgus monkey and mouse VISTA are shown. The signal peptide (Sig) and transmembrane domain (TMD) sequence positions are marked. The conserved histidine residues in all three species are shown in bold and underlined; the conserved histidine residues in human and cynomolgus monkey are shown only in bold. Figure 1CA model of the three-dimensional structure of the human VISTA immunoglobulin domain is shown. Histidine residues are depicted as sphere and stick traces.

[0008] Figures 2A to 2B A model is shown in which histidine residues in the extracellular domain of VISTA confer counter-receptor selectivity for acidic pH rather than physiological pH. Figure 2A The equilibrium between the absence and presence of protonation of the pyrrolic ammonium group (NH) in a histidine residue is shown. The pK of histidine in solution is a is 6.5, which indicates that histidine residues are more likely to be protonated, and therefore positively charged, at pH 6.5 or lower than at higher pH. Figure 2B The following model is shown, in which VISTA selectively binds to P-selectin glycoprotein ligand 1 (PSGL-1) or other counter-receptors and ligands ("VISTA-R") at acidic pH. Therefore, antibodies that bind to the extracellular domain of VISTA at acidic pH, but not at physiological pH, may be important for inhibiting or modulating VISTA activity.

[0009] Figure 3 VISTA surface expression levels (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 are shown. VISTA is expressed on many tumor-infiltrating leukocytes, particularly myeloid cells. The tumor microenvironment is typically acidic, enabling VISTA to engage counter-receptors and ligands.

[0010] Figures 4A to 4E It was shown that VISTA selectively binds to leukocytes and PSGL-1 at acidic pH, barely binds at neutral pH, and this binding can be blocked by anti-VISTA antibodies. Figure 4A The left figure shows a representative histogram of recombinant VISTA polymers conjugated with fluorescence for binding to activated human CD4+T cells. From dark gray to light gray, the filled histograms depict the binding at pH 7.0, 6.5, 6.4, 6.3, 6.1 and 6.0. Some histograms are marked with their corresponding pH. The non-VISTA control polymer binding at pH 6.0 is shown as an unfilled histogram. In the right figure, the average MFI of VISTA (circles) and control (triangles) polymers bound to activated human CD4+T cells from two donors at different pH values ​​is shown by a graph. Figure 4BRepresentative histograms of recombinant VISTA polymer binding to peripheral blood mononuclear cells (PBMC) at pH 6.0 and pH 7.4 are shown. From dark gray to light gray, the filled histograms depict binding to CD19+B cells, CD4+T cells, CD8+T cells, CD56+NK cells, and CD14+ monocytes at pH 6.0. The unfilled solid and dashed boundary histograms depict binding to total PBMC lymphocytes and monocytes at pH 7.4, respectively. Figure 4C Representative binding of recombinant VISTA polymers to activated human CD4+ T cells in the presence of anti-VISTA blocking antibodies (squares) or non-VISTA specific isotype-matched control antibodies (circles) is shown. Antibody concentrations are plotted on a logarithmic scale. Nonlinear regression is also shown. Triangles depict background signals from activated human CD4+ T cells not stained with recombinant VISTA polymers. Figure 4D Representative two-dimensional flow cytometry plots showing the binding of recombinant VISTA multimers to heparan sulfate-deficient Chinese hamster ovary (CHO) cells (cell line pGSD-677, American Type Culture Collection) transfected to express human PSGL-1 at pH 6.0. Figure 4C Multimer binding was performed in the presence of the anti-VISTA blocking antibody shown in . Cells 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. From dark gray to light gray, filled histograms depict binding to CD8+ T cells, CD11b+ myeloid cells, and CD4+ T cells at pH 6.0. Unfilled histograms depict binding to total splenocytes at pH 7.4.

[0011] 5A to 5D We show that VISTA preferentially mediates T cell inhibition and cell:cell adhesion at acidic pH, and both effects can be reversed with anti-VISTA blocking antibodies. Figure 5A Shown are representative cell:cell conjugate formation at pH 6.0 and 7.0 between 293T cells expressing hVISTA or vector control (plotted on the y-axis) and CHO cells endogenously expressing cell surface heparan sulfate on the x-axis. Figure 5Bis a graph of the frequency of cell conjugates formed between the same cells in the presence of anti-VISTA blocking antibodies, anti-VISTA non-blocking antibodies, or isotype-matched non-VISTA specific control antibodies at pH 6.0. Figure 5C Representative graphs of luciferase activity generated by Jurkat (human T cell line) cells expressing the NFkB luciferase reporter gene 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 different pH values ​​are shown. Anti-VISTA blocking antibodies (squares) or isotype-matched non-VISTA specific control antibodies (circles) were added to the co-cultured cells. Figure 5D In Figure 5A The data shown in are plotted as the fold increase in luciferase signal relative to the control with anti-VISTA antibody treatment ("effect size").

[0012] Figures 6A to 6G It was shown that VISTA can be found in endosomes within cells, particularly Rab11+ recycling endosomes, and can be recycled to and from the cell surface via endosomal trafficking. Figure 6A Co-localization of VISTA, Rab5 (early endosomal marker), Rab7 (late endosomal marker), and Rabl 1 (recycling endosomal marker) in 293T cells expressing human VISTA is shown. Figure 6B The colocalization of VISTA and Rab11 in human monocytes is shown. Intracellular VISTA colocalizes with Rab11+ recycling endosomes. A non-VISTA binding control antibody ("cAb") of the same isotype as the VISTA antibody did not detectably bind to monocytes. Figure 6C Binding of three anti-VISTA antibodies to recombinant VISTA at pH 7.4 (black), 6.7 (dark grey), and 6 (light grey) is shown. Figure 6D Shown are the susceptibility of VISTA-expressing acute myeloid leukemia (AML) cell lines to killing by the same anti-VISTA antibody 1 (inverted triangle), 2 (circle), 3 (square) or a non-VISTA-specific control antibody (triangle) with a cathepsin B-sensitive linker and a cytotoxic payload. Cell viability (CellTiter-Glo LU) is plotted on the y-axis, and antibody concentration is plotted on the x-axis. Figure 6E hVISTA binding of anti-VISTA antibody 3 was compared to that of an engineered variant ("VISTA mAb 3c") that did not exhibit impaired binding at acidic pH. Figure 6F Antibody drug-conjugate assays are shown comparing the potency of anti-VISTA antibodies 3 (squares) and 3c (diamonds). Figure 6G A schematic diagram of endosomal trafficking is shown, in which VISTA is recycled to and from the cell surface via early endosomes and recycling endosomes.

[0013] 7A to 7F Shown is how to design and screen an anti-VISTA antibody variant library for acidic pH-selective antibodies. Figure 7A The amino acid substitutions made in the VH CDR 3 of the anti-human VISTA antibody clone P1-061029 (abbreviated as '029) are shown to generate the '029 library for screening. In order to potentially improve binding to the histidine-rich region of VISTA at acidic pH, the library allows substitution with negatively charged amino acids aspartic acid and glutamic acid and pH-responsive histidine. X = H, D or E. The sequences in brackets were removed from the synthesis to avoid introducing negative values. A total of 647 unique sequences of P1-061029 HCDR3 with 1-2 mutations were synthesized. Figure 7B The procedure for iterative screening and selection of the 029 library for acidic pH selective antibody variants is shown. R indicates the number of selection rounds. Figure 7C Representative two-dimensional flow cytometry data are shown, which show the variant library after 9 rounds of selection. VISTA binding is plotted on the y-axis, and variant antibody expression is plotted on the x-axis. Binding data at various antibody concentrations and pH are shown. Figure 7D Figures showing binding of P1-061029 and its progeny clones to human VISTA at pH 6.0 and 7.4. Figure 7E A graph showing the off-rates of P1-061029 and its progeny clones from human VISTA at pH 6.0. Figure 7F Shown are SPR binding data for antibodies P1-068761, P1-068767, and P1-061029 to human VISTA at pH 6.0 and pH 7.4.

[0014] Figures 8A to 8F Acidic pH-selective cell binding, blocking, and effector activities of VISTA antibodies P1-068761 and P1-068767 are shown. Figure 8A and Figure 8B The acidic pH selective antibody P1-068761 ( Figure 8A ) and P1-068767( Figure 8B ) at approximately pH 6.0 (circles; Figure 8A), 6.1 (square; third-highest curve), 6.2 (triangle; second-highest curve), 6.4 (inverted triangle; fourth-highest curve, close to the pH 6.1 curve), 6.6 (diamond; fourth curve from the bottom), 7.0 (circle; third curve from the bottom), 7.2 (square; second curve from the bottom), and 8.1 (unfilled triangle; Figure 8A The cells were stained below the bottom curve in Figure 3. Binding was detected using a fluorescently conjugated anti-human IgG secondary antibody. Figure 8C Binding of P1-068767 (circles) and an isotype-matched nonspecific control antibody (triangles) at 3125 ng / mL to Raji cells ectopically expressing human VISTA at different pH values ​​is shown. 50 That is, the pH at which 50% of the P1-068767 binding is lost is approximately 6.6. Figure 8D Isotype-matched nonspecific control antibody binding to human monocytes is shown (filled and unfilled circles, pH 7.0 and 6.0, respectively), anti-VISTA mAb2 ("Control," see Figure 6C Mean fluorescence intensity (MFI) of PI-068761 (filled and unfilled triangles, pH 7.0 and 6.0, respectively), PI-068767 (filled and unfilled inverted triangles, pH 7.0 and 6.0, respectively). Binding was detected by a fluorescently conjugated anti-human IgG secondary antibody. Figure 8E Comparable blocking of binding of recombinant VISTA multimers to activated human CD4+ T cells at pH 6.0 by P1-061029 (squares), P1-068761 (triangles), and P1-068767 (inverted triangles) is shown, while a non-VISTA-specific control antibody (circles) did not block VISTA binding. Figure 8F Shown at physiological pH PI-068761 (triangle) and PI-068767 (inverted triangle) in mediating antibody-dependent cellular cytotoxicity (ADCC) in the reduced titer.Also shown is PI-061029 (square), non-VISTA specific positive control antibody (circle) and non-VISTA specific negative control antibody (diamond).The NK cell specific lysis of target cells is plotted on the y-axis as a percentage of the total number of target cells, and the antibody concentration is plotted on the x-axis.Also shown is nonlinear regression.

[0015] Figure 9 Figure 2 shows enhanced pharmacokinetics (PK) of acidic pH selective anti-VISTA antibodies in cynomolgus monkeys. Figure 6C ), VISTA antibody 3 ("acidic pH sensitive", square, see Figure 6C ) or P1-068767 (triangles)-treated cynomolgus monkeys over time.

[0016] Figure 10A and Figure 10B Shown are the binding effects of mutations in the acidic pH-selective anti-VISTA antibodies '761 and '767. Figure 10A Shown are kinetic binding data for the P1-068761 revertants at pH 7.4, pH 6.7, and pH 6.0, along with the positions of their revertants relative to P1-068761. Figure 10B Shown are kinetic binding data for the P1-068767 revertants at pH 7.4, pH 6.7, and pH 6.0, along with the positions of their revertants relative to P1-068767.

[0017] Figures 11A to 11C Epitope grouping and localization of various anti-VISTA antibodies are shown. Figure 11A VISTA epitope competition by P1-068761 and P1-068767 compared to P1-061029 and a VISTA antibody control is shown. Figure 11B and Figure 11C Shown are the results of the experiments with non-blocking hVISTA antibodies (mAb1; Figure 11C ) compared to the hVISTA blocking antibodies listed in Table 14 ( Figure 11B ). Amino acid residues 66 (H) and 162 (A) are indicated to show the orientation of the molecule. Histidine residues are in grey, and epitope residues are in black.

[0018] 12A to 12C The following imaged capillary isoelectric focusing (icIEF) data are shown: Figure 12A :P1-061029、 Figure 12B :P1-068761 and Figure 12C : P1-068767. The isoelectric point of the major species (pI main) and the pI marker are indicated.

[0019] Figure 13A and Figure 13B An alignment of the variable regions of the '029 and '015 progeny clones is shown. Figure 13A An alignment of the amino acid sequences of the variable regions of '029 and its progeny clones is shown. Figure 13B An alignment of the amino acid sequences of the variable regions of '015 and its progeny clones is shown. DETAILED DESCRIPTION

[0020] definition

[0021] In this application, the use of "or" means "and / or" unless otherwise stated. In the context of multiple dependent claims, the use of "or" refers back to more than one preceding independent or dependent claim only in an alternative manner. The terms "comprising," "including," and "having" are used interchangeably herein. According to the present invention, an "isolated" molecule is a molecule that has been removed from its natural environment. Thus, the term "isolated" does not necessarily reflect the degree to which a molecule has been purified.

[0022] The term "polypeptide" refers to a polymer of amino acid residues and is not limited to a minimum length. A "protein" may include one or more polypeptides. Such polymers of amino acid residues may contain natural or non-natural amino acid residues and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. The definition encompasses both full-length proteins and fragments thereof. The term also includes post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In addition, for the purposes of the present invention, "polypeptide" or "protein" refers to a polypeptide or protein comprising modifications such as deletions, additions, and substitutions (usually conservative in nature) to the native sequence, as long as the protein maintains the desired activity. These modifications may be intentional (such as by site-directed mutagenesis) or may be accidental (such as by mutations in the host producing the protein or errors caused by PCR amplification). A protein may include two or more polypeptides.

[0023] "VISTA" is an abbreviation for inhibitor of T cell activating protein containing V domain immunoglobulins, 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" herein refers to the human VISTA protein. The amino acid sequence of hVISTA (including its signal peptide) is provided in SEQ ID NO: 1, while the sequence without the signal peptide is provided in SEQ ID NO: 2. (See Sequence Listing below.) The extracellular domain or "ECD" or "VISTA-ECD" of VISTA refers to the portion of the VISTA protein that is located in the extracellular space, which in the case of hVISTA comprises amino acids 1-162 of SEQ ID NO: 2. (See also Figure 1B .) The "IgV domain" portion of hVISTA comprises residues 5-135 of SEQ ID NO:2.

[0024] The term "leader peptide" or "leader sequence" refers to a sequence of amino acid residues located at the N-terminus of a polypeptide that promotes secretion of the polypeptide from mammalian cells. The leader sequence can be cleaved after the polypeptide is exported from the mammalian cell, thereby forming the mature protein. Leader sequences can be natural or synthetic and can be heterologous or homologous to the protein to which they are attached.

[0025] The term "antibody" or "Ab" is used in the broadest sense herein and covers various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies) and antibody fragments, as long as they exhibit the desired antigen-binding activity. As used herein, the term refers to a molecule comprising at least the complementary determining region (CDR) 1, CDR2 and CDR3 of a heavy chain and at least CDR1, CDR2 and CDR3 of a light chain, wherein the molecule is capable of binding to an antigen. The term antibody includes but is not limited to fragments capable of binding to an antigen, such as 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 (e.g., mice, cynomolgus monkeys, etc.).

[0026] 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).

[0027] The term "heavy chain variable region" or "VH" refers to the region comprising the heavy chain complementarity determining region (CDR) 1, framework region (FR) 2, CDR2, FR3, and CDR3 of the heavy chain. In some embodiments, the heavy chain variable region further comprises at least a portion of FR1 and / or at least a portion of FR4. As described below, in some embodiments, the heavy chain CDR1 comprises residues 26-35 of the VH SEQ ID NO herein; the heavy chain CDR2 comprises residues 50-66 of the VH SEQ ID NO herein, and the heavy chain CDR3 comprises residues 99-110 of the VH SEQ ID NO herein. In other embodiments, if specified, the heavy chain CDR1 corresponds to Kabat residues 31 to 35; the heavy chain CDR2 corresponds to Kabat residues 50 to 65; and the heavy chain CDR3 corresponds to Kabat residues 95 to 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, as in the Sequence Listing or Table 2 below.

[0028] 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.

[0029] The term "light chain variable region" or "VL" refers to the region comprising the light chain CDR1, FR2, HVR2, FR3, and HVR3. In some embodiments, the light chain variable region also comprises FR1 and / or FR4. As described below, in some embodiments, the light chain CDR1 comprises residues 24-35 of the VL SEQ ID NO herein; the light chain CDR2 comprises residues 51-57 of the VL SEQ ID NO herein, and the light chain CDR3 comprises residues 90-98 of the VL SEQ ID NO herein. In other embodiments, if specified, the light chain CDR1 corresponds to Kabat residues 24 to 34; the light chain CDR2 corresponds to Kabat residues 50 to 56; and the light chain CDR3 corresponds to Kabat residues 89 to 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 herein, as specified in the sequence listing.

[0030] "Chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is derived from a specific source or species, while the rest of the heavy chain and / or light chain is derived from a different source or species. In some embodiments, a chimeric antibody refers to an antibody comprising at least one variable region from a first species (such as mouse, rat, cynomolgus monkey, etc.) and at least one constant region from a second species (such as 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 variable regions of the chimeric antibody are from the first species, and all constant regions of the chimeric antibody are from the second species.

[0031] A "humanized antibody" refers to an antibody in which at least one amino acid in the framework region of a non-human variable region has been replaced by the corresponding amino acid from a human variable region. In some embodiments, the humanized antibody comprises at least one human constant region or a fragment thereof. In some embodiments, the humanized antibody is Fab, scFv, (Fab')2, etc.

[0032] As used herein, "human antibodies" refer to antibodies produced in humans, antibodies produced in non-human animals (e.g., ), and antibodies selected using in vitro methods such as phage display, where the antibody library is based on human immunoglobulin sequences.

[0033] As used herein, "VISTA antibody" or "anti-VISTA antibody" refers to an antibody that specifically binds to VISTA under at least certain conditions (such as acidic pH). In some embodiments, the antibody can be a "huVISTA antibody" or "anti-huVISTA antibody," indicating that it specifically binds to the human VISTA protein under at least certain conditions (such as at acidic pH). For example, a VISTA antibody that specifically binds to the extracellular domain (ECD) of VISTA can be referred to as a "VISTA-ECD antibody."

[0034] In some embodiments, the antibody can bind to VISTA with higher affinity at acidic pH compared to neutral and / or physiological pH. In some embodiments, the antibody can bind to VISTA with higher affinity at acidic pH and only negligibly or non-specifically bind at neutral and / or physiological pH.

[0035] The "K" of antibodies binding to proteins (such as VISTA-ECD protein) D The "dissociation constant" or "dissociation constant" is a measure of the affinity or specific binding of an antibody to a protein (e.g., VISTA-ECD protein). A lower K DIndication with higher K D Improved binding or affinity compared to K D The “off-rate” or k for antibodies and peptides 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 in a system associate and dissociate. Therefore, a slower dissociation rate (where the association rate remains approximately constant) results in a higher overall affinity and thus a lower K. D As used herein, a particular value of "or less" of k off Indicator k off Or the "off-rate" is as specified or slower than the specified rate.

[0036] The term "specific binding" or "specifically binds" or similar terms refers to the K for the binding of two polypeptides (such as an antibody and its polypeptide target). D is smaller than that between two random peptides under the same conditions. In other words, K D The smaller size is due to nonspecific aggregation of peptides in the system.

[0037] In some embodiments, the antibody specifically binds to the VISTA-ECD protein at a specific pH or within a pH range. "Acidic" pH herein generally refers to a pH less than 7.0, "alkaline" pH generally refers to a pH higher than 7.0, and "neutral" pH generally refers to a pH of about 7.0. "Physiological pH" herein refers to the pH under normal (i.e., non-cancerous) physiological conditions, for example, 7.35 to 7.45 or 7.3 to 7.4, such as about 7.4. Physics herein used in the context of the combination of two molecules (such as VISTA and VISTA binding partner or VISTA and T cells), such as "combining under acidic conditions" or "combining under physiological conditions", etc., refer to combining under acidic pH and combining under physiological pH, respectively.

[0038] When referring to "blocking" or "inhibiting" the binding of a ligand (or receptor) or competing antibody to a receptor (or ligand) alone or on a cell, the binding is blocked if there is a statistically significant overall reduction (e.g., 50% or greater overall reduction, e.g., 75%, 80%, 85%, 90%, 95% or greater overall reduction) compared to a control. For example, an "anti-VISTA blocking antibody" is one that can block the binding of VISTA to PSGL-1 or another VISTA ligand or receptor or heparan sulfate proteoglycan under at least certain conditions (e.g., at acidic pH).

[0039] As used herein, "tumor model" 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 natural mouse tumor assay systems. In some cases, a tumor model can allow tracking of tumor size or growth after treatment with an antibody, and / or tracking the presence of immune cells (such as specific types of T cells or NK cells) in the tumor to determine whether the antibody has triggered or enhanced an immune response.

[0040] As used herein, the term "immunostimulator" refers to a molecule that stimulates the immune system by acting as an agonist of an immunostimulatory molecule (including a costimulatory molecule) or acting as an antagonist of an immunosuppressive molecule, including a costimulatory molecule. An immunostimulatory molecule or an immunosuppressive molecule can be an immune checkpoint regulator, such as VISTA or another B7 family member or another molecule as further described below. An immunostimulatory agent can be a biological agent (such as an antibody or antibody fragment), other proteins or vaccines, or can be a small molecule drug. "Immunostimulatory molecules" include receptors or ligands that enhance, stimulate, induce or otherwise "turn on" an immune response. Immunostimulatory molecules as defined herein include costimulatory molecules. "Immunosuppressive molecules" include receptors or ligands that alleviate, inhibit, suppress or otherwise "turn off" an immune response. Immunosuppressive molecules as defined herein include costimulatory molecules. Such immunostimulatory and immunosuppressive molecules can be receptors or ligands found, for example, on immune cells (such as T cells) or on cells participating in innate immunity (such as NK cells).

[0041] "Percent (%) amino acid sequence identity" and "homology" with respect to peptide, polypeptide or antibody sequences are defined as the percentage of amino acid residues in a candidate sequence that are identical with 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 and not considering any conservative substitutions as part of the sequence identity. Alignment for determining percent amino acid sequence identity can be achieved in a variety of ways well known in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGN™ (DNASTAR) software. One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm required to achieve maximum alignment over the full length of the compared sequences.

[0042] The term "trigger" or "enhance" refers to the initiation or increase of any event (such as protein ligand binding) or the initiation or increase of any biological activity (such as immune response) or phenotypic characteristic, or refers to an increase in the incidence, degree or likelihood of the activity or characteristic. "Trigger" or "enhancement" refers to the start or increase of an activity, function and / or amount compared to a reference. The triggering or enhancement does not have to be complete. For example, in certain embodiments, "enhancement" means the ability to cause an overall increase of 20% or greater. In another embodiment, "enhancement" means the ability to cause an overall increase of 50% or greater. In yet another embodiment, "enhancement" means the ability to cause an overall increase of 75%, 85%, 90%, 95% or greater.

[0043] The term "inhibition" or "inhibit" more generally refers to a reduction or cessation of any event (such as protein ligand binding) or a reduction or cessation of any phenotypic characteristic or a reduction or cessation of the incidence, extent or likelihood of that characteristic. "Reduce" or "inhibit" refers to a reduction or blockade of activity, function and / or amount compared to a reference. The inhibition or reduction does not have to be complete. For example, in certain embodiments, "reduce" or "inhibit" means the ability to cause an overall reduction of 20% or greater. In another embodiment, "reduce" or "inhibit" means the ability to cause an overall reduction of 50% or greater. In yet another embodiment, "reduce" or "inhibit" means the ability to cause an overall reduction of 75%, 85%, 90%, 95% or greater.

[0044] As used herein, "treating" encompasses any administration or application of a therapeutic agent for a disease in a human, and includes inhibiting the progression of a disease or the disease or one or more symptoms of a disease, inhibiting or slowing the disease or its progression or one or more of its symptoms, arresting its development, partially or completely relieving the disease or one or more of its symptoms, or preventing the recurrence of one or more symptoms of a disease.

[0045] The terms "subject" and "patient" are used interchangeably herein to refer to a human.

[0046] The term "effective amount" or "therapeutically effective amount" refers to an amount of a drug that is effective for treating a disease or disorder in a subject, for example, to partially or completely alleviate one or more symptoms. In some embodiments, an effective amount refers to an amount effective to achieve the desired therapeutic or preventive result at the necessary dosage and for the necessary period of time.

[0047] The term "cancer" is used herein to refer to a population of cells that exhibits an abnormally high level of proliferation and growth. Cancer can be benign (also known as a benign tumor), 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 the proliferation or growth of one or more cells comprising a cancer, which results in a corresponding increase in the size or extent of the cancer.

[0048] Examples of cancers suitable for the methods of treatment herein include, but are not limited to, carcinomas, lymphomas, blastomas, sarcomas, and leukemias. 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), lung adenocarcinoma, lung squamous carcinoma, peritoneal cancer, hepatocellular carcinoma, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, 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, liver cancer, 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).

[0049] Administration "in combination with" one or more additional therapeutic agents includes simultaneous (concurrent) and consecutive (sequential) administration in any order.

[0050] 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 with a therapeutic agent, which together comprise a "pharmaceutical composition" for administration to a subject. A pharmaceutically acceptable carrier is non-toxic to the recipient at the dosages and concentrations used and is compatible with the other ingredients of the formulation. A pharmaceutically acceptable carrier is suitable for the formulation being used. For example, if the therapeutic agent is to be administered orally, the carrier can be a gel capsule. If the therapeutic agent is to be administered subcutaneously, it is ideal that the carrier is non-irritating to the skin and does not cause injection site reactions.

[0051] A "chemotherapeutic agent" is a chemical compound that can be used to treat cancer. Examples of chemotherapeutic agents that can be administered in the methods herein include, but are not limited to, alkylating agents such as thiotepa and Cyclophosphamide; alkyl sulfonates, such as busulfan, improsulfan, and piposulfan; aziridines, such as benzodopa, carboquinone, meturedopa, and uredopa; ethyleneimines and methylamelamines, including hexamethylmelamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide, and trimethylolomelamine; polyacetylamines (especially bullatacin and bullatacinone); camptothecins (including synthetic analogs); topotecan); bryostatin; callystatin; CC-1065 (including its synthetic analogs adolesin, carzelesin, and biszelesin); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); caudate; duocarmycin (including synthetic analogs, KW-2189, and CB1-TM1); eleutherobin; pancratistatin; sarcodictyin; spongistatin; nitrogen mustards (e.g., chlorambucil), naphthalene mustard, chlorophosphamide, estramustine, ifosfamide, dichloromethyldiethylamine, mechlorethamine hydrochloride, oxide hydrochloride), melphalan, nembixin, phenesterine, phenylephrine, trofosfamide, uracil nitrogen mustard; nitrosoureas such as carmustine, chlorozostatin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as enediyne antibiotics (e.g., calicheamicins, especially calicheamicin gamma and calicheamicin omega (see, e.g., Agnew, Chem Intl. Ed. Engl., 33:183-186 (1994); dynemicins, including dynemicin A; bisphosphonates such as clodronate; esperamicin; and neocarcinogen chromophores and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, oxytetracycline, azaserine, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycin, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, Doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrroline-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins (such as mitomycin C), mycophenolic acid, nogamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, enimex), zinostatin, zorubicin; antimetabolites, such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs, such as denopterin, methotrexate, pteropterin, and trimetrexate; purine analogs, such as fludarabine, 6-mercaptopurine, thiamiprine, and thioguanine; pyrimidine analogs, such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and floxuridine; androgens, such as calusterone and dromostanolone propionate. propionate, epitiostanol, mepitiostane, testolactone; antiadreners such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as folic acid; aceglucuronolide; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornithine; eliritamide; epothilone; etoglucid; gallium nitrate nitrate); hydroxyurea; Lentinan; lonidainine;Maytansinoids, such as maytansine and ansamitocin; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-acetylhydrazine; procarbazine; Polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A, and anguidine); urethan; vindesine; dacarbazine; mannitol mustard; dibromomannitol; dibromodulcitol; pipobroman; gacytosine; cytarabine ("Ara-C"); cyclophosphamide; thiotepa; taxanes, such as Paclitaxel (Bristol-Myers Squibb Oncology, Princeton, NJ), Cremophor-free albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, IL) and Docetaxel ( -Poulenc Rorer, Antony, France); chloranbucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin, and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; Vinorelbine; novantrone; teniposide; edatrexate; daunorubicin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including regimens of irinotecan with 5-FU and leucovorin); the topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids, such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin, including oxaliplatin regimens (FOLFOX); inhibitors that reduce cell proliferation such as PKC-α, Raf, H-Ras, and EGFR (e.g., erlotinib). ) and VEGF-A inhibitors, and pharmaceutically acceptable salts, acids or derivatives of any of the foregoing.

[0052] Other non-limiting exemplary chemotherapeutic agents that can be administered in the methods herein include antihormonal agents that act to modulate or inhibit hormonal effects on cancer (such as antiestrogens and selective estrogen receptor modulators (SERMs)), including, for example, tamoxifen (including Tamoxifen), raloxifene, droloxifene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and Toremifene; aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as 4(5)-imidazole, aminoglutethimide, megestrol acetate, exemestane, formestane, fadrozole, Vorozole, Letrozole and 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 abnormal cell proliferation, such as PKC-α, Ralf, and H-Ras; ribozymes, such as inhibitors of VEGF expression (e.g., ribozymes) and HER2 expression inhibitors; vaccines, such as gene therapy vaccines, e.g. vaccine, Vaccines and vaccine; rIL-2; Topoisomerase 1 inhibitors; rmRH; and pharmaceutically acceptable salts, acids or derivatives of any of the foregoing.

[0053] "Anti-angiogenic agent" or "angiogenesis inhibitor" refers to a small 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 directly or indirectly inhibits angiogenesis, vasculogenesis, or undesirable vascular permeability. It should be understood that anti-angiogenic agents include those that bind to angiogenic factors or their receptors and block the angiogenic activity of the angiogenic factors or their receptors. For example, anti-angiogenic agents that can be administered in the methods herein can include antibodies or other antagonists to angiogenic agents, such as those directed against VEGF-A (e.g., bevacizumab). ) or VEGF-A receptors (such as KDR receptor or Flt-1 receptor), anti-PDGFR inhibitors (such as (imatinib mesylate), small molecules that block VEGF receptor signaling (e.g., PTK787 / ZK2284, SU6668, / SU11248 (sunitinib malate), AMG706 or those described in, for example, International Patent Application WO2004 / 113304). Anti-angiogenic agents also include natural angiogenesis inhibitors, such as angiostatin, endostatin, and the like. See, e.g., Klagsbrun and D'Amore (1991) Annu. Rev. Physiol. 53:217-39; Streit and Detmar (2003) Oncogene 22:3172-3179 (e.g., Table 3 lists antiangiogenic therapies for malignant melanoma); Ferrara and Alitalo (1999) Nature Medicine 5(12):1359-1364; Tonini et al. (2003) Oncogene 22:6549-6556 (e.g., Table 2 lists known antiangiogenic factors); and Sato (2003) Int. J. Clin. Oncol. 8:200-206 (e.g., Table 1 lists antiangiogenic agents used in clinical trials).

[0054] As used herein, a "growth inhibitory agent" refers to a compound or composition that inhibits the growth of cells (such as cells expressing VEGF) in vitro or in vivo. Thus, the growth inhibitory agent that can be administered in the methods herein can be one that significantly reduces the percentage of cells in the S phase (such as cells expressing VEGF). Examples of growth inhibitory agents include, but are not limited to, agents that block cell cycle progression (outside of the S phase), such as agents that induce G1 arrest and M phase arrest. Classical M phase blockers include periwinkle (vincristine and vinblastine), taxanes, and topoisomerase II inhibitors (such as doxorubicin, epirubicin, daunorubicin, etoposide, and bleomycin). Agents that block G1 also penetrate into S phase arrest, such as DNA alkylating agents (such as tamoxifen, prednisone, dacarbazine, methoxyethylamine, cisplatin, methotrexate, 5-fluorouracil, and cytarabine). Further information can be found in Mendelsohn and Israel, eds., The Molecular Basis of Cancer, Chapter 1, Murakami et al., entitled "Cell cycle regulation, oncogenes, and antineoplastic drugs" (WB Saunders, Philadelphia, 1995), e.g., page 13. Taxanes (paclitaxel and docetaxel) are anticancer drugs both derived from the yew tree. Docetaxel ( Rhone-Poulenc Rorer) is paclitaxel ( 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.

[0055] The term "anti-tumor composition" refers to a composition that contains at least one active therapeutic agent that can be used to treat cancer. 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), and other agents for treating cancer. Platelet-derived growth factor inhibitors (e.g. (imatinib mesylate), COX-2 inhibitors (e.g., celecoxib), interferons, CTLA4 inhibitors (e.g., the anti-CTLA antibody ipilimumab ), PD-1 or PD-L1 inhibitors (e.g. ), 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-β, BlyS, APRIL, BCMA, CTLA4, TIM3, or VEGF receptors, TRAIL / Apo2, and other biologically active and organic chemical agents, etc. Combinations thereof are also encompassed within the present disclosure.

[0056] Antibodies that specifically bind to VISTA-ECD at acidic pH

[0057] Since VISTA has a large number of histidine residues in its ECD, it is closely related to neutral pH, especially near the pK value of histidine. a Its folding and overall structure, as well as the surface available for binding of ligands (such as antibodies), may be different at acidic pH compared to pH 6.5. Since the tumor microenvironment is often acidic, for antibodies to bind to VISTA in those microenvironments, they may need to bind specifically to VISTA at acidic pH, where at least some surface histidine residues are more likely to be protonated.

[0058] The sequence table below provides the amino acid sequence of human VISTA (hVISTA) with or without a signal peptide (SEQ ID NO: 1 and SEQ ID NO: 2 (mature hVISTA)). 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 stem region is at amino acid residues 172-194 of SEQ ID NO: 1 and amino acid residues 136-162 of SEQ ID NO: 2; the transmembrane domain is at amino acid residues 195-216 of SEQ ID NO: 1 and amino acid residues 163-184 of SEQ ID NO: 2. Amino acid residues 187 of SEQ ID NO: 1 and 155 of SEQ ID NO: 2 (bold and underlined) can be D or E, which represents the polymorphism in hVISTA. This residue is shown in bold and underlined. Therefore, SEQ ID NO: 1 and SEQ ID NO: 2 contain two human polymorphisms at this residue. The histidine residue in the ECD of VISTA is shaded gray.

[0059] Anti-VISTA antibodies (Ab) can specifically bind to VISTA-ECD or its fragment (e.g., the IgV domain of the fragment comprising VISTA or a region comprising, for example, amino acids 20-95, 20-70, 35-70, 35-95, 35-127, or 37-125 of SEQ ID NO: 2) at acidic pH. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 7.0. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 6.8. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 6.5. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 6.3. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 6.0. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 5.8. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 5.5. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 5.3. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH less than pH 5.0.

[0060] Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 7.0. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 6.5. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 6.0. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.5-pH 7.0. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.5-pH 6.5. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 6.0-6.5.

[0061] Also provided herein is a method for producing a 10 -6 M or smaller K DAn Ab that binds to a VISTA-ECD protein (e.g., hVISTA-ECD or a fragment thereof comprising the IgV domain of VISTA or a region from hVISTA comprising, for example, amino acids 20-95, 20-70, 35-70, 35-95, 35-127, or 37-125 of SEQ ID NO: 2). In some embodiments, the Ab is administered at 10 -7 M or smaller K D In some embodiments, Ab is bound to -8 M or smaller K D In some embodiments, Ab is bound to -9 M's K D In some embodiments, Ab is bound to -10 M or smaller K D For example, Ab can bind at a pH of 6.5 or lower with a -8 M or smaller K D Binds to VISTA-ECD protein.

[0062] Also provided herein is an Ab that is 10 -6 M or smaller K D In some embodiments, the Ab is bound to the VISTA-ECD protein at 10 -7 M or smaller K D In some embodiments, Ab is bound to -8 M or smaller K D In some embodiments, Ab is bound to -9 M's K D In some embodiments, Ab is bound to -10 M or smaller K D For example, Ab can bind at a pH of 6.5 or lower, for example, in the pH range of 6.0-6.5. -7 M or smaller K D Binds to VISTA-ECD protein. In addition, the Ab can bind to VISTA-ECD protein at a pH of 6.5 or lower, for example, in the pH range of 6.0-6.5. -8 M or smaller K D Binds to VISTA-ECD protein. The Ab can bind to VISTA-ECD protein at a pH of 6.5 or lower, for example, in the pH range of 6.0-6.5. -9 M or smaller K D Binds to hVISTA-ECD.

[0063] Also provided herein are Abs that specifically bind to a VISTA-ECD protein (such as hVISTA-ECD or a fragment thereof comprising the IgV domain of VISTA or a region from hVISTA comprising, for example, 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 less, wherein the k off is 10 -5 s -1 In some embodiments, Ab has a 10 -4 s -1 or smaller k off In some embodiments, Ab has a 2 10 -4 s -1 or smaller k off In some embodiments, Ab has a 5 10 -4 s -1 or smaller k off In some embodiments, Ab has a 7 10 -4 s -1 or smaller k off In some embodiments, Ab has a pH of 10 at 25°C or 37°C. -3 s -1 or smaller k off In some embodiments, Ab has a 2 10 -3 s -1 or smaller k off In some embodiments, Ab has a 5 10 -3 s -1 or smaller k off In some embodiments, Ab has a 7 10 -3 s -1 or smaller k off In some embodiments, Ab has a pH of 10 at 25°C or 37°C. -2 s -1 or smaller k off In some embodiments, Ab has a pH of 10 at 25°C or 37°C. -1 s -1 or smaller k off For example, Ab can be expressed at a pH of 6.5 or lower for 10 min at 25°C or 37°C. -3 s -1 or smaller k offThe Ab can bind specifically to the VISTA-ECD protein at a pH of 6.5 or lower and at 25°C or 37°C for 10 -3 s -1 or smaller k off The Ab can bind specifically to the hVISTA-ECD protein at a pH of 6.5 or lower and at 25°C or 37°C for 10 -2 s -1 or smaller k off Binds specifically to the VISTA-ECD protein.

[0064] Provided herein are Abs that bind to a VISTA-ECD protein (such as hVISTA-ECD or a fragment thereof comprising the IgV domain of VISTA or a region from hVISTA comprising, e.g., amino acids 20-95, 20-70, 35-70, or 35-95, 35-95, 35-127, or 37-125 of SEQ ID NO: 2), e.g., at a pH of 6.5 or less, wherein (i) K D is 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 less and (ii) k off Rate is 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 less or 10 -1 s -1 or less, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to a VISTA-ECD protein at a pH of 6.5 or less, where K D is 10 -7 M or less and k off Rate is 10 -3 s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, where K D is 10 -8 M or less and k off Rate is 10 - 3s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, where K D is 10 -8 M or less and k off Rate is 10 -2 s -1 or less, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -7 M or less and k off Rate is 10 -3 s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -9 M or less and k off Rate is 10 -3 s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -9 M or less and k off Rate is 10 -2 s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -8 M or less and k off Rate is 10 -4 (or 2, 5 or 7 10 -4 )s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -8 M or less and k off Rate is 10 -5 (or 2, 5 or 7 10 -5 )s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -9 M or less and k off Rate is 10 -4 (or 2, 5 or 7 10-4 )s -1 or less, as measured, for example, at 25°C or 37°C. The Ab can bind to hVISTA-ECD at a pH of 6.5 or less, where K D is 10 -9 M or less and k off Rate is 10 -5 (or 2, 5 or 7 10 -5 )s -1 or less, as measured, for example, at 25°C or 37°C.

[0065] Provided herein are, for example, at a pH of 6.5 or less and at 25°C or 37°C for 10 4 M -1 s -1 or higher k on Ab that specifically binds to VISTA-ECD protein. In some such embodiments, Ab can be expressed as 10 5 M -1 s -1 or higher k on In some such embodiments, Ab can be combined with 10 6 M -1 s -1 or higher k on In some such embodiments, Ab can be combined with 10 7 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, where k on is 10 6 M -1 s -1 or higher, as measured, for example, at 25° C. or 37° C. For example, the Ab can bind to the ECD of hVISTA at a pH of 6.5 or lower, where k on is 10 6 M -1 s -1 or higher, as measured, for example, at 25°C or 37°C.

[0066] Provided herein are Abs that bind to a VISTA-ECD protein, e.g., at a pH of 6.5 or lower, wherein (i) K D is 10 - 6 M or smaller, 10 -7 M or smaller, 10 -8 M or smaller, 10 -9 M or smaller or 10 -10M or less, and (ii) k on is 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, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to a VISTA-ECD protein at a pH of 6.5 or lower, where the K D is 10 -7 M or less and k on Rate is 10 6 Ms -1 or higher, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to a VISTA-ECD protein at a pH of 6.5 or lower, where the K D is 10 -8 M or less and k on Rate is 10 6 Ms -1 or higher, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to hVISTA-ECD at a pH of 6.5 or lower, where K D is 10 -7 M or less and k on Rate is 10 6 Ms -1 or higher, as measured, for example, at 25° C. or 37° C. For example, an Ab can bind to hVISTA-ECD at a pH of 6.5 or lower, where K D is 10 -8 M or less and k on Rate is 10 6 Ms -1 or higher, as measured, for example, at 25°C or 37°C.

[0067] In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -7 M or less and where k off is 10 -5 s -1 or less, 2 10 -5 s -1 or smaller, 510 -5 s-1 or less, 7 10 -5 s -1 or smaller, 10 -4 s -1 or less, 2 10 -4 s -1 or less, 5 10 -4 s -1 or less, 7 10 -4 s -1 or smaller, 10 -3 s -1 or less, 2 10 -3 s -1 or less, 5 10 -3 s -1 or less, 7 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1 or less, as measured, for example, at 25°C or 37°C. In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, where K D is 10 -9 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1 or less, as measured, for example, at 25°C or 37°C. In some such embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, where K D is 10 -10 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1 or less, as measured, for example, at 25°C or 37°C.

[0068] In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -7 M or less and where k on is 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, as measured, for example, at 25°C or 37°C. In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -8 M or less and where k on is 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, as measured, for example, at 25°C or 37°C. In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -9 M or less and where k on is 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, as measured, for example, at 25°C or 37°C. In some such embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -10 M or less and where kon is 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, as measured, for example, at 25°C or 37°C.

[0069] In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -7 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1 or less, as measured, for example, at 25°C or 37°C, and k on is 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, as measured, for example, at 25°C or 37°C. In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -8 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1or less, as measured, for example, at 25°C or 37°C, and k on is 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, as measured, for example, at 25°C or 37°C. In some embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -9 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1 or less, as measured, for example, at 25°C or 37°C, and k on is 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, as measured, for example, at 25°C or 37°C. In some such embodiments, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or lower, where K D is 10 -10 M or less and where k off is 10 -5 s -1 or smaller, 10 -4 s -1 or smaller, 10 -3 s -1 or smaller, 10 -2 s -1 or less or 10 -1 s -1or less, as measured, for example, at 25°C or 37°C, and k on is 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, as measured, for example, at 25°C or 37°C.

[0070] Also as described above, in some of the above-mentioned embodiments, the VISTA-ECD protein is a portion of hVISTA-ECD or hVISTA-ECD (e.g., an IgV domain). In some of the above-mentioned embodiments, Ab can specifically bind to an epitope comprising SEQ ID NO:2 amino acids 20-95. In some of the above-mentioned embodiments, Ab can specifically bind to an epitope comprising SEQ ID NO:2 amino acids 20-70. In some of the above-mentioned embodiments, Ab can specifically bind to an epitope comprising SEQ ID NO:2 amino acids 35-95. In some of the above-mentioned embodiments, Ab can specifically bind to an epitope comprising SEQ ID NO:2 amino acids 35-70. In some of the above-mentioned embodiments, the epitope is a three-dimensional epitope that not only comprises the above-mentioned portion of SEQ ID NO:2: one of residues 20-95, 20-70, 35-95, or 35-70, but also comprises another portion of SEQ ID NO:2, such as residues 95-105 of SEQ ID NO:2. In certain embodiments, Ab binds to the epitope of hVISTA bound by Ab described in WO 2015 / 097536. For example, Ab can compete or cross-compete for binding to hVISTA with Ab disclosed in WO 2015 / 097536. In certain embodiments, Ab binds to the conformational epitope of human VISTA. In certain embodiments, Ab binds to the following conformational epitope, which comprises or is present in SEQ ID NO:2 residues 103-111 and SEQ ID NO:2 of human VISTA. In certain embodiments, Ab binds to the following conformational epitope, which comprises or is present in SEQ ID NO:2 residues 24-36, 54-65, and 100-102 of human VISTA. In certain embodiments, Ab binds to the following conformational epitope, which comprises amino acid residues in the FG loop of human VISTA. In some embodiments, the Ab binds to a polypeptide comprising amino acid residues 35 to 127 and / or 37-125 of SEQ ID NO:2.In some embodiments, the Ab binds to a VISTA ECD polypeptide comprising amino acid residues 350-127 of SEQ ID NO: 2, or a portion thereof, but the antibody does not bind or binds with reduced affinity to a VISTA ECD polypeptide or a portion thereof comprising amino acid substitutions, wherein the substitution (1) is of 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) is of 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 antibodies have the same binding characteristics (or substantially the same binding characteristics) as the antibodies described herein, e.g., in the Examples.

[0071] Some of the above antibodies may show different binding affinities for the VISTA-ECD protein depending on the pH value. 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 may bind to the VISTA-ECD protein with a 10 affinity at pH 6.5 and pH 7.0. -7 M or smaller K D Bind to the VISTA-ECD protein (at a constant temperature of, for example, 25°C or 37°C) such that the K at pH 6.5 is D K at pH 7.0 D Some of these Abs can be expressed at pH 6.5 and pH 7.0 at 10 -8 M or smaller K D Bind to the VISTA-ECD protein (at a constant temperature of, for example, 25°C or 37°C) such that the K at pH 6.5 is D K at pH 7.0 D Some of these Abs can be expressed at pH 6.5 and pH 7.0 at 10 -8 M or smaller K D Bind to the hVISTA-ECD protein (at a constant temperature of, for example, 25°C or 37°C) such that the K at pH 6.5 is D K at pH 7.0 D within 1.5 times of .

[0072] Certain Abs that specifically bind to VISTA-ECD proteins under acidic conditions (e.g., at pH 6.5 or lower) can bind to VISTA-ECD proteins 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 proteins under acidic conditions (e.g., at pH 6.5 or lower) can have insignificant, e.g., barely detectable, binding to VISTA-ECD proteins under neutral, physiological, and / or alkaline conditions. For example, in some embodiments, an Ab can bind to VISTA-ECD proteins with a pH of 10 at pH 6.5. -8 M or smaller K D and at pH 7.0 and / or pH 7.4 with a concentration greater than 10 -8 M's K D In some such embodiments, the Ab can bind to the VISTA-ECD protein at pH 6.5 at 10 -8 M or smaller K D and at pH 7.0 and / or pH 7.4 with a K value greater than that at pH 6.5. D 1.5 times of K D Binding to VISTA-ECD protein. In certain embodiments, a pH-sensitive Ab is provided that specifically binds to a VISTA-ECD protein, wherein the K at pH 6.5 is D At least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 300-fold, 500-fold, 1000-fold, or 5000-fold lower than at pH 7.0 (at a constant temperature of, e.g., 25° C. or 37° C.). For example, in some cases an Ab binds to a VISTA-ECD protein where the K is lower relative to pH 7.0 and / or pH 7.4 or higher. D At least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 300-fold, 500-fold, 1000-fold, or 5000-fold smaller at pH 6.0 (at a constant temperature of, for example, 25°C or 37°C).

[0073] In certain embodiments, the Ab specifically binds to a VISTA-ECD protein, wherein k off The k under acidic conditions is lower than that under neutral, physiological or alkaline conditions. off In certain embodiments, an Ab is provided that binds to a VISTA-ECD protein under acidic conditions, wherein the k at pH 6.5 is off than k at pH 7.0 and / or pH 7.4 offThe off-rate is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold lower than that at pH 7.0 and / or pH 7.4, as measured, for example, at 25°C or 37°C. In other words, the off-rate is slower at acidic pH than at neutral pH. For example, in some embodiments, the Ab specifically binds to the VISTA-ECD protein, wherein the k is lower relative to pH 7.0 and / or pH 7.4. off The rate is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold lower at pH 6.0, as measured, for example, at 25° C. or 37° C. In certain embodiments, an Ab that binds to a VISTA-ECD protein is provided, wherein the k at pH 6.5 is off K at pH 7.4 off At least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold lower, as measured, for example, at 25° C. or 37° C. In some embodiments, the Ab specifically binds to the VISTA-ECD protein, wherein the k at pH 6.0 relative to pH 7.4 is off The rate is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold slower, as measured, for example, at 25° C. or 37° C. In certain embodiments, an Ab that binds to a VISTA-ECD protein is provided, wherein the k at pH 6.0-6.5 is off Compared with k at pH 7.0-7.4 off At least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1000-fold lower, as measured, for example, at 25°C or 37°C.

[0074] In certain embodiments, the Ab specifically binds to a VISTA-ECD protein, wherein k is greater than or equal to 0.01 relative to neutral, physiological, or alkaline conditions. on In certain embodiments, an Ab is provided that binds to a VISTA-ECD protein under acidic conditions, wherein the k at pH 6.5 is higher than the k at pH 6.5. on than k at pH 7.0 and / or pH 7.4 on At least 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, or 1000-fold higher, as measured, for example, at 25° C. or 37° C. For example, in some embodiments, the Ab specifically binds to the aVISTA-ECD protein, wherein k on 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, as measured, for example, at 25°C or 37°C.

[0075] In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH where at least one histidine residue, such as His 98 in SEQ ID NO: 1, is protonated. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH where the majority of the histidine residues in the ECD are protonated, which is expected to be pH 6.5 or lower, such as between pH 6.0 and pH 6.5.

[0076] Also encompassed herein are Abs that specifically bind to the VISTA-ECD protein with higher affinity at neutral, physiological, or alkaline pH relative to acidic pH, provided that the binding affinity remains high at acidic pH. For example, an Ab may bind to the VISTA-ECD protein with a higher affinity at both pH 6.5 and pH 7.0. -8 M or smaller K D The Ab binds to the VISTA-ECD protein, but the Ab binds to the VISTA-ECD protein with a K that is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold, 300-fold, 500-fold, 1000-fold lower at pH 7.0 than at pH 6.5. D combination.

[0077] Abs having one or more of the above characteristics of this moiety are also encompassed herein. D 、k off 、k on , 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 above, and may also have pan-binding or pH-sensitive or pH-selective binding properties as described above, such as by K at different pHs. D 、k off or k on One or more of the behaviors shown.

[0078] In any of the above embodiments, the Ab can 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 an antigen-binding fragment (e.g., a Fab fragment, a Fab' fragment, a (Fab')2 fragment, a scFv fragment, a Fv fragment), or the Ab can be a chimeric antibody, a humanized antibody, or a human antibody, or the Ab can be a bispecific or multispecific antibody.

[0079] Several different methods can be used to determine the extent of antibody binding to the VISTA-ECD protein at a given pH. For example, by surface plasmon resonance (SPR), such as by An exemplary SPR assay involves the use of an immobilized capture reagent (e.g., Anti-Human Fc Capture Kit, GE Healthcare Cat. No. BR-1008-39 or Anti-mouse capture kit, GE Healthcare catalog number BR-1008-39) is used to capture one or more antibodies on a CM4 sensor chip and flow a concentration series of VISTA antigens as analytes to determine binding kinetics and affinity in a running buffer with a desired pH. In one embodiment, VISTA is injected at two to five concentrations (e.g., 0.1nM, 1nM, 10nM, 100nM, 500nM) in the range of 0.1nM to 500nM at a flow rate of 30uL / min, a maximum association time of four minutes, and a maximum dissociation time of ten minutes. Between binding cycles, the capture surface is regenerated according to the manufacturer's instructions for the corresponding capture kit. All data are double-referenced using a reference flow cell and a blank injection. T200 evaluation software was used to fit data with simple 1:1 kinetics to a Langmuir binding model with mass shift. The SPR method described in the Examples can also be used.

[0080] The affinity of Ab for VISTA ECD polypeptides can be determined using cells expressing VISTA ECD polypeptides, PSGL-1 or heparan sulfate on their surfaces, the method including flow cytometry, and wherein the binding of Ab to cell-bound VISTA-ECD is determined at a given pH (e.g., pH 6.5 or lower). An exemplary flow cytometry assay includes the following: 293T cells or other cells ectopically expressing hVISTA ECD are resuspended in a buffer consisting of HBSS+1% BSA, adjusted to the desired pH (e.g., adjusted to pH 6.0 with MES or adjusted to pH 7.4 with HEPES). Anti-hVISTA Ab (e.g., human IgG) is serially diluted from about 20 μg / mL and incubated with resuspended cells at 4°C for 30 minutes. The cells are then washed twice with the same buffer to maintain the desired pH (e.g., pH 6.0 or 7.4) and incubated with a second antibody conjugated to a fluorophore that recognizes an antibody (e.g., human IgG) and is stable at a reduced pH. The cells are then washed as before and immediately acquired on a BD Fortessa or other flow cytometer, but not fixed. The affinity of the Ab for the VISTAECD polypeptide can be determined as described in the Examples.

[0081] In certain embodiments, the Ab bound to hVISTA ECD blocks, for example, the binding of hVISTA to its binding partner (e.g., VISTA receptor) on a cell. Inhibition or blocking can be 100% or at least 99%, 95%, 90%, 85%, 80%, 75% or 50%. In certain embodiments, Ab binds to VISTA-ECD protein at acidic pH (e.g., pH 6.5 or lower) and inhibits the 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, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 7.0 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 6.8 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 6.5 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 6.3 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 6.0 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 5.8 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 5.5 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, Ab specifically binds to VISTA-ECD protein at a pH lower than pH 5.3 and inhibits the binding of VISTA to its binding partner by at least 50%. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH below pH 5.0 and inhibits binding of VISTA to its binding partner by at least 50%.

[0082] Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 7.0 and inhibit the binding of VISTA to its binding partner by at least 50%. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 6.5 and inhibit the binding of VISTA to its binding partner by at least 50%. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.0-pH 6.0 and inhibit the binding of VISTA to its binding partner by at least 50%. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.5-pH 7.0 and inhibit the binding of VISTA to its binding partner by at least 50%. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 5.5-pH 6.5 and inhibit the binding of VISTA to its binding partner by at least 50%. Certain Abs specifically bind to the VISTA-ECD protein at a pH in the range of pH 6.0-6.5 and inhibit the binding of VISTA to its binding partner by at least 50%. Inhibition of binding can be determined as described in the Examples.

[0083] The VISTA binding partner can 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 can also be, for example, a heparan sulfate proteoglycan present on certain cells.

[0084] Inhibition of binding to a VISTA binding partner can be determined by measuring the 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., activated or unactivated CD4+ T cells, CD8+ T cells), NK cells, or other cells to which VISTA binds, in the presence and absence of the antibody. An exemplary experiment that can be used to determine whether an antibody inhibits the binding of VISTA to its binding partner or T cells expressing the binding partner is a flow cytometry assay, such as an assay comprising resuspending human peripheral blood mononuclear cells from donor blood, buffy coats, or leukopak in a buffer composed of HBSS+1% BSA adjusted to the desired pH (e.g., to pH 6.0 with MES or to pH 7.4 with HEPES). The cells were then incubated at 4 ° C with 20 μg / mL recombinant chimeric protein consisting of hVISTA ECD (VISTA-Fc) fused to human IgG1 Fc and various concentrations of candidate VISTA blocking antibodies or control antibodies for 30 minutes. The cells were then washed twice in the same buffer to maintain the desired pH (e.g., pH 6.0 or 7.4) and incubated for another 30 minutes at 4 ° C with a fluorophore-conjugated secondary antibody that recognizes VISTA-Fc, rather than a candidate blocking antibody or control antibody, and were stable at reduced pH values. The cells were then washed as before and immediately acquired on a BD Fortessa or other flow cytometer, but not fixed. The inhibition of binding can be determined, for example, as described in the Examples.

[0085] In certain embodiments, Ab as described herein can trigger or enhance an immune response, such as an antigen-specific immune response. In certain embodiments, Ab stimulates T cell activity, particularly under acidic pH (as found in a tumor microenvironment). The 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. The stimulation of T cell activity can also be measured using, for example, the Jurkat assay described in the Examples.

[0086] In certain embodiments, the Abs described herein inhibit cell adhesion, which can be measured as described in the Examples.

[0087] The activity of anti-VISTA Ab can also be shown in monocyte assays, ADCC assays, and ADCP assays, particularly at acidic pH (as found in the tumor microenvironment).

[0088] In certain embodiments, the anti-VISTA Ab inhibits tumor growth in a tumor model, such as a human VISTA knock-in tumor model.

[0089] As shown in the examples herein, anti-VISTA Ab is recycled in the endosome to enhance the pharmacokinetic (PK) properties of the antibody, i.e., half-life, requiring anti-VISTA antibodies to bind to VISTA under acidic conditions. Therefore, as further described herein, anti-VISTA Abs that bind to VISTA at low pH (e.g., pH 6.5 or lower) are also expected to have a longer acceptable half-life relative to VISTA antibodies that do not bind to VISTA at acidic pH.

[0090] Exemplary hVISTA-ECD-binding Abs

[0091] Provided herein are Abs that preferentially bind to hVISTA(ECD) at acidic pH (e.g., under acidic conditions) relative to physiological or neutral pH.

[0092] In certain embodiments, an anti-hVISTA Ab comprises a heavy chain variable region ("VH") comprising a VH CDR1, CDR2, and / or CDR3 of any anti-hVISTA antibody provided herein. In certain embodiments, an anti-hVISTA Ab comprises a VH comprising a VH CDR1, CDR2, and CDR3 of any anti-hVISTA Ab provided herein. In certain embodiments, an anti-hVISTA Ab comprises P1-061029 or P1-061015 or 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, P 1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068 748, P1-068750, P1-068752, P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068 761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100 fF、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、VH of a CDR1, CDR2 and / or CDR3 of a VH of 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 VH CDR1, CDR2, and CDR3 of each of these classes comprise amino acid positions 26-35 (VH CDR1), 50-66 (VH CDR2), and 99-110 (VH CDR3) of the VH sequence of each of the above-mentioned antibody classes provided in the sequence listing below. The CDRs are also underlined and in bold in each of the VH sequences of the above-mentioned antibody classes provided in the sequence listing below.

[0093] In certain embodiments, an anti-hVISTA Ab comprises a VH comprising a VH CDR1, CDR2, and CDR3 of any anti-hVISTA Ab provided herein. Ab contains 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, and P1-061015. 68736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P1-068754, P1-068761_E55A, P1-0 68761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E3 0D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1 -068761_E56N_E100fF、P1-068761_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 .The VH CDR1, CDR2, and CDR3 of one of P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF are shown. The VL CDR1, CDR2, and CDR3 of each of these classes comprise amino acid positions 24-35 (VL CDR1), 51-57 (VL CDR2), and 90-98 (VL CDR3) of the VL sequence of each of the above-mentioned antibody classes provided in the sequence listing below. The CDRs are also underlined and in bold in each of those sequences.

[0094] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising a VH CDR1, CDR2 and / or CDR3 of any anti-hVISTA Ab provided herein and a VL comprising a CDR1, CDR2 and / or CDR3 of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises a VH comprising a VH CDR1, CDR2 and CDR3 of any anti-hVISTA Ab provided herein and a VL comprising a CDR1, CDR2 and CDR3 of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTAAb comprises a monoclonal antibody comprising P1-061029 or P1-061015, or 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, P1-068769, P1-068771, P1-068773, P1-068775, 1-069067, 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, P1-068752, P1-068754, P1-068761_E55A, P1-068761_H10 0G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-0 68761_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、P1-068761_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, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D _E100fF VH CDR1, CDR2 and / or CDR3 and a VH containing P1-061029 or P1-061015 or its descendants 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, P 1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1 -068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P1-0 68754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_ E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H1 00G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF , P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E 100fF, 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, P1-0687 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 P1-068767_E30D_E100fF.

[0095] In some embodiments, an anti-hVISTA Ab may comprise:

[0096] (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;

[0097] (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;

[0098] (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;

[0099] (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;

[0100] (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;

[0101] (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;

[0102] (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;

[0103] (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;

[0104] (i) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068769 and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068769;

[0105] (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;

[0106] (k) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068773 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068773;

[0107] (1) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068775 and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068775;

[0108] (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;

[0109] (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;

[0110] (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;

[0111] (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;

[0112] (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;

[0113] (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;

[0114] (s) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-069071 and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-069071;

[0115] (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;

[0116] (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;

[0117] (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;

[0118] (w) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068736 and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068736;

[0119] (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;

[0120] (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;

[0121] (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;

[0122] (aa) VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068744 and VL comprising VL CDR1, CDR2, and CDR3 of P1-068744;

[0123] (bb) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068746 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068746;

[0124] (cc) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068748 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068748;

[0125] (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;

[0126] (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;

[0127] (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;

[0128] (gg) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E55A and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E55A;

[0129] (hh) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_H100G, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_H100G;

[0130] (ii) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E56N;

[0131] (jj) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E55A_E56N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E55A_E56N;

[0132] (kk) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D;

[0133] (11) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E55A, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E55A;

[0134] (mm) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G;

[0135] (nn) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G;

[0136] (oo) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N;

[0137] (pp) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E100fF, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E100fF;

[0138] (qq) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF;

[0139] (rr) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF;

[0140] (ss) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF;

[0141] (tt) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF;

[0142] (uu) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E32Y;

[0143] (vv) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E55A and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E55A;

[0144] (ww) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E56N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E56N;

[0145] (xx) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E32Y and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E32Y;

[0146] (yy) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_H100G, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_H100G;

[0147] (zz) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068761_E32Y_E100fF, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068761_E32Y_E100fF;

[0148] (aaa) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_D102V and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_D52N_D102V;

[0149] (bbb) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_D52N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_D52N;

[0150] (ccc) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_E55A and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_D52N_E55A;

[0151] (ddd) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_E55A_D102V and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E55A_D102V;

[0152] (eee) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_D102V and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_D102V;

[0153] (fff) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E55A and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767_E55A;

[0154] (ggg) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_D52N and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E30D_D52N;

[0155] (hhh) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_D102V and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E30D_D102V;

[0156] (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;

[0157] (jjj) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_E55A and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E30D_E55A;

[0158] (kkk) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V;

[0159] (111) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF, and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF;

[0160] (mmm) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF;

[0161] (nnn) a VH comprising the amino acid sequence of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF and a VL comprising the VL CDR1, CDR2, and CDR3 of P1-068767_E100fF;

[0162] (ooo) A VH comprising the amino acid sequence of VH CDR1, CDR2 and CDR3 of P1-068767_E30D_E100fF and a VL comprising the VL CDR1, CDR2 and CDR3 of P1-068767_E30D_E100fF.

[0163] Likewise, the following sequence listing 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 HC constant region is indicated in the table), and indicates the positions of their VH CDR1, CDR2, and CDR3, and VL CDR1, CDR2, and CDR3, by amino acid residue and using bold and underlined text for the CDRs in each VH and VL sequence. Thus, for example, the VH CDR1 of P1-061029 comprises amino acids 26-35 of SEQ ID NO: 67, while the VH CDR2 comprises amino acids 50-66 of SEQ ID NO: 67, and the VH CDR3 comprises amino acids 99-110 of SEQ ID NO: 67, and so on, as indicated by the bold and underlined amino acids of SEQ ID NO: 67 as shown in the sequence listing.

[0164] In certain embodiments, the anti-hVISTAAb comprises a VH comprising the amino acid sequence of the VH of any anti-hVISTAAb provided herein. Individual VH sequences for specific antibody species provided herein are listed in the Sequence Listing. In certain embodiments, the anti-hVISTAAb comprises an antibody comprising P1-061029 or P1-061015, or 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, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-0687 50. P1-068752, P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E 30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-0 68761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E5 6N. N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D,In certain embodiments, the anti-hVISTAAb comprises a VH CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VH CDRs of any anti-hVISTAAb provided herein, and comprises a VH 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 anti-hVISTAAb provided herein. In certain embodiments, the anti-hVISTAAb comprises a VH comprising an amino acid sequence that is identical to 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, P1-06 1015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P 1-068752, 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_E30 D_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, P1-0687 67_D52N_E55A, P1-068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, The amino acid sequence of the VH of 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 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. In certain embodiments, the anti-hVISTAAb comprises a VH consisting of the amino acid sequence of the VH of any anti-hVISTAAb provided herein. In certain embodiments, the anti-hVISTAAb comprises a monoclonal antibody consisting of P1-061029 or P1-061015, or 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 , P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1 -068766, P1-068748, P1-068750, P1-068752, P1-068754, P1-068761_E55A, P 1-068761_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, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761 _H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_E 32Y, 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, P1-06 8767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1- The VH comprises the amino acid sequence of the VH of P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF.

[0165] 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, the anti-hVISTAAb comprises an antibody comprising P1-061029 or P1-061015, or 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, P1-06907 3. P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068 740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-06 8752, P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E5 6N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P 1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E5 6N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E 100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-06876 1_E32Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E3 0D_E32Y, P1-068761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-0687 67_D52N_D102V, P1-068767_D52N, P1-068767_D52N_E55A, P1-068767_ E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D5 2N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55A,In certain embodiments, the anti-hVISTA Ab comprises a VL CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VL CDRs of any anti-hVISTA Ab provided herein, and comprises a VL 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 anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises a VL CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VL CDRs of any anti-hVISTA Ab provided herein, and comprises a VL 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 anti-hVISTA Ab provided herein. Ab comprises a VL comprising an amino acid sequence identical to 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, P1-0690 65. 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, P1-068752, P1-068754 , P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-0 68761_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, P1 -068767_E55A_D102V, P1-068767_D102V, P1-068767_E55A, P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_ The amino acid sequence of the VL of 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 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. In certain embodiments, the anti-hVISTA Ab comprises a VL consisting of the amino acid sequence of the VL of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises P1-061029 or P1-061015 or its progeny 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, P1-061015, P1-0687 36. P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P 1-068750, P1-068752, P1-068754, P1-068761_E55A, P1-068761_H100G, P1-0 68761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55 A. P1-068761_E56N_H100G, P1-068761_E30D_H100G, 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_E 32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068761_E32Y_H1 00G, 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_E55 A. P1-068767_E30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-06876 The VL of the VL of P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF is composed of the amino acid sequence.

[0166] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising the amino acid sequence of the VH of any anti-hVISTA Ab provided herein, and comprises a VL comprising the amino acid sequence of the VL of any anti-hVISTA Ab provided herein. In certain embodiments of these embodiments, the anti-hVISTA Ab comprises P1-061029 or P1-061015 or 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, P 1-069075, P1-069077, P1-061015, P1-068736, P1-068738, 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_E3 0D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P 1-068761_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、a VH having the amino acid sequence of the VH of 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; and a VL having the amino acid sequence of P1-061029 or P1-061015. In certain embodiments, the anti-hVISTAAb comprises a monoclonal antibody comprising P1-061029 or P1-061015, or 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, P1-069 067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-0687 42. P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P1-068754, P1-068761_E55A, P1-068761_H100G, P1-0687 61_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H1 00G, 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_E3 2Y, 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_E 30D_D52N, P1-068767_E30D_D102V, P1-068767_E30D, P1-068767_E30D_E55 A, VH and VL of the amino acid sequences of VH and VL of P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF.

[0167] In certain embodiments, the anti-hVISTA Ab comprises a VH CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VH CDR of any anti-hVISTA Ab provided herein and a VL CDR1, CDR2, and CDR3 comprising the amino acid sequence of the VL CDR of any anti-hVISTA Ab provided herein, and further comprises a VH and VL each 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 corresponding VH and VL of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises all 6 CDRs of the anti-hVISTA Ab provided herein, and further comprises a VH and VL each 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 corresponding VH and VL of any anti-hVISTA Ab provided herein. The corresponding VH and VL of Ab, such as P1-061029 or P1-061015 or their descendants 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, P1-061015, P1-068 736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P1-0 68754, 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, P1-068 761_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_E30 D, P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF VH and VL 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 VH and VL amino acid sequences. In certain embodiments, the anti-hVISTA Ab comprises a VH and VL consisting of the amino acid sequences of the VH and VL of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises each of P1-061029 or P1-061015 or 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. 015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-0687 66. P1-068748, P1-068750, P1-068752, P1-068754, P1-068761_E55A, P1-0 68761_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, P1-068761_E3 2Y, P1-068761_E32Y_E55A, P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, P1-068 761_E32Y_H100G, P1-068761_E32Y_E100fF, P1-068767_D52N_D102V, P1-068767_D5 2N, 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, P1-0687 The VH and VL of the VH and VL of P1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF or P1-068767_E30D_E100fF are respectively.

[0168] Anti-hVISTA Abs may contain:

[0169] (a) a VH comprising the amino acid sequence of VH of P1-061029 and a VL comprising the amino acid sequence of VL of P1-061029;

[0170] (b) a VH comprising the amino acid sequence of VH of P1-061015 and a VL comprising the amino acid sequence of VL of P1-061015;

[0171] (c) a VH comprising the amino acid sequence of VH of P1-068757 and a VL comprising the amino acid sequence of VL of P1-068757;

[0172] (d) a VH comprising the amino acid sequence of VH of P1-068759 and a VL comprising the amino acid sequence of VL of P1-068759;

[0173] (e) a VH comprising the amino acid sequence of VH of P1-068761 and a VL comprising the amino acid sequence of VL of P1-068761;

[0174] (f) a VH comprising the amino acid sequence of VH of P1-068763 and a VL comprising the amino acid sequence of VL of P1-068763;

[0175] (g) a VH comprising the amino acid sequence of VH of P1-068765 and a VL comprising the amino acid sequence of VL of P1-068765;

[0176] (h) a VH comprising the amino acid sequence of VH of P1-068767 and a VL comprising the amino acid sequence of VL of P1-068767;

[0177] (i) a VH comprising the amino acid sequence of VH of P1-068769 and a VL comprising the amino acid sequence of VL of P1-068769;

[0178] (j) a VH comprising the amino acid sequence of VH of P1-068771 and a VL comprising the amino acid sequence of VL of P1-068771;

[0179] (k) a VH comprising the amino acid sequence of VH of P1-068773 and a VL comprising the amino acid sequence of VL of -068773;

[0180] (1) a VH comprising the amino acid sequence of VH of P1-068775 and a VL comprising the amino acid sequence of VL of P1-068775;

[0181] (m) a VH comprising the amino acid sequence of VH of P1-069059 and a VL comprising the amino acid sequence of VL of P1-069059;

[0182] (n) a VH comprising the amino acid sequence of VH of P1-069061 and a VL comprising the amino acid sequence of VL of P1-069061;

[0183] (o) a VH comprising the amino acid sequence of VH of P1-069063 and a VL comprising the amino acid sequence of VL of P1-069063;

[0184] (p) a VH comprising the amino acid sequence of VH of P1-069065 and a VL comprising the amino acid sequence of VL of P1-069065;

[0185] (q) a VH comprising the amino acid sequence of VH of P1-069067 and a VL comprising the amino acid sequence of VL of P1-069067;

[0186] (r) a VH comprising the amino acid sequence of VH of P1-069069 and a VL comprising the amino acid sequence of VL of P1-069069;

[0187] (s) a VH comprising the amino acid sequence of VH of P1-069071 and a VL comprising the amino acid sequence of VL of P1-069071;

[0188] (t) a VH comprising the amino acid sequence of VH of P1-069073 and a VL comprising the amino acid sequence of VL of P1-069073;

[0189] (u) a VH comprising the amino acid sequence of VH of P1-069075 and a VL comprising the amino acid sequence of VL of P1-069075;

[0190] (v) a VH comprising the amino acid sequence of VH of P1-069077 and a VL comprising the amino acid sequence of VL of P1-069077;

[0191] (w) a VH comprising the amino acid sequence of VH of P1-068736 and a VL comprising the amino acid sequence of VL of P1-068736;

[0192] (x) a VH comprising the amino acid sequence of VH of P1-068738 and a VL comprising the amino acid sequence of VL of P1-068738;

[0193] (y) a VH comprising the amino acid sequence of VH of P1-068740 and a VL comprising the amino acid sequence of VL of P1-068740;

[0194] (z) a VH comprising the amino acid sequence of VH of P1-068742 and a VL comprising the amino acid sequence of VL of P1-068742;

[0195] (aa) a VH comprising the amino acid sequence of VH of P1-068744 and a VL comprising the amino acid sequence of VL of P1-068744;

[0196] (bb) a VH comprising the amino acid sequence of VH of P1-068746 and a VL comprising the amino acid sequence of VL of P1-068746;

[0197] (cc) a VH comprising the amino acid sequence of VH of P1-068748 and a VL comprising the amino acid sequence of VL of P1-068748;

[0198] (dd) a VH comprising the amino acid sequence of VH of P1-068750 and a VL comprising the amino acid sequence of VL of P1-068750;

[0199] (ee) a VH comprising the amino acid sequence of VH of P1-068752 and a VL comprising the amino acid sequence of VL of P1-068752;

[0200] (ff) a VH comprising the amino acid sequence of VH of P1-068754 and a VL comprising the amino acid sequence of VL of P1-068754;

[0201] (gg) a VH comprising the amino acid sequence of VH of P1-068761_E55A and a VL comprising the amino acid sequence of VL of P1-068761_E55A;

[0202] (hh) a VH comprising the amino acid sequence of VH of P1-068761_H100G and a VL comprising the amino acid sequence of VL of P1-068761_H100G;

[0203] (ii) a VH comprising the amino acid sequence of VH of P1-068761_E56N and a VL comprising the amino acid sequence of VL of P1-068761_E56N;

[0204] (jj) a VH comprising the amino acid sequence of VH of P1-068761_E55A_E56N and a VL comprising the amino acid sequence of VL of P1-068761_E55A_E56N;

[0205] (kk) a VH comprising the amino acid sequence of VH of P1-068761_E30D and a VL comprising the amino acid sequence of VL of P1-068761_E30D;

[0206] (11) a VH comprising the amino acid sequence of VH of P1-068761_E30D_E55A and a VL comprising the amino acid sequence of VL of P1-068761_E30D_E55A;

[0207] (mm) a VH comprising the amino acid sequence of VH of P1-068761_E56N_H100G and a VL comprising the amino acid sequence of VL of P1-068761_E56N_H100G;

[0208] (nn) a VH comprising the amino acid sequence of VH of P1-068761_E30D_H100G and a VL comprising the amino acid sequence of VL of P1-068761_E30D_H100G;

[0209] (oo) a VH comprising the amino acid sequence of the VH of P1-068761_E30D_E56N and a VL comprising the amino acid sequence of the VL of P1-068761_E30D_E56N;

[0210] (pp) a VH comprising the amino acid sequence of VH of P1-068761_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_E100fF;

[0211] (qq) a VH comprising the amino acid sequence of VH of P1-068761_E55A_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_E55A_E100fF;

[0212] (rr) a VH comprising the amino acid sequence of VH of P1-068761_H100G_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_H100G_E100fF;

[0213] (ss) a VH comprising the amino acid sequence of VH of P1-068761_E30D_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_E30D_E100fF;

[0214] (tt) a VH comprising the amino acid sequence of VH of P1-068761_E56N_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_E56N_E100fF;

[0215] (uu) a VH comprising the amino acid sequence of VH of P1-068761_E32Y and a VL comprising the amino acid sequence of VL of P1-068761_E32Y;

[0216] (vv) a VH comprising the amino acid sequence of VH of P1-068761_E32Y_E55A and a VL comprising the amino acid sequence of VL of P1-068761_E32Y_E55A;

[0217] (ww) a VH comprising the amino acid sequence of VH of P1-068761_E32Y_E56N and a VL comprising the amino acid sequence of VL of P1-068761_E32Y_E56N;

[0218] (xx) a VH comprising the amino acid sequence of VH of P1-068761_E30D_E32Y and a VL comprising the amino acid sequence of VL of P1-068761_E30D_E32Y;

[0219] (yy) a VH comprising the amino acid sequence of VH of P1-068761_E32Y_H100G and a VL comprising the amino acid sequence of VL of P1-068761_E32Y_H100G;

[0220] (zz) a VH comprising the amino acid sequence of VH of P1-068761_E32Y_E100fF and a VL comprising the amino acid sequence of VL of P1-068761_E32Y_E100fF;

[0221] (aaa) a VH comprising the amino acid sequence of VH of P1-068767_D52N_D102V and a VL comprising the amino acid sequence of VL of P1-068767_D52N_D102V;

[0222] (bbb) a VH comprising the amino acid sequence of VH of P1-068767_D52N and a VL comprising the amino acid sequence of VL of P1-068767_D52N;

[0223] (ccc) a VH comprising the amino acid sequence of VH of P1-068767_D52N_E55A and a VL comprising the amino acid sequence of VL of P1-068767_D52N_E55A;

[0224] (ddd) a VH comprising the amino acid sequence of VH of P1-068767_E55A_D102V and a VL comprising the amino acid sequence of VL of P1-068767_E55A_D102V;

[0225] (eee) a VH comprising the amino acid sequence of VH of P1-068767_D102V and a VL comprising the amino acid sequence of VL of P1-068767_D102V;

[0226] (fff) a VH comprising the amino acid sequence of VH of P1-068767_E55A and a VL comprising the amino acid sequence of VL of P1-068767_E55A;

[0227] (ggg) a VH comprising the amino acid sequence of VH of P1-068767_E30D_D52N and a VL comprising the amino acid sequence of VL of P1-068767_E30D_D52N;

[0228] (hhh) a VH comprising the amino acid sequence of VH of P1-068767_E30D_D102V and a VL comprising the amino acid sequence of VL of P1-068767_E30D_D102V;

[0229] (iii) a VH comprising the amino acid sequence of VH of P1-068767_E30D and a VL comprising the amino acid sequence of VL of P1-068767_E30D;

[0230] (jjj) a VH comprising the amino acid sequence of VH of P1-068767_E30D_E55A and a VL comprising the amino acid sequence of VL of P1-068767_E30D_E55A;

[0231] (kkk) a VH comprising the amino acid sequence of VH of P1-068767_E100fF_D102V and a VL comprising the amino acid sequence of VL of P1-068767_E100fF_D102V;

[0232] (111) a VH comprising the amino acid sequence of VH of P1-068767_E55A_E100fF and a VL comprising the amino acid sequence of VL of P1-068767_E55A_E100fF;

[0233] (mmm) a VH comprising the amino acid sequence of VH of P1-068767_D52N_E100fF and a VL comprising the amino acid sequence of VL of P1-068767_D52N_E100fF;

[0234] (nnn) a VH comprising the amino acid sequence of VH of P1-068767_E100fF and a VL comprising the amino acid sequence of VL of P1-068767_E100fF; or

[0235] (ooo) a VH comprising the amino acid sequence of the VH of P1-068767_E30D_E100fF and a VL comprising the amino acid sequence of the VL of P1-068767_E30D_E100fF. The anti-hVISTA Ab may comprise:

[0236] (a) a VH comprising the VH CDRs of the VH of P1-061029 and a VL comprising the VL CDRs of P1-061029, 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 P1-061029;

[0237] (b) a VH comprising the VH CDRs of the VH of P1-061015 and 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;

[0238] (c) a VH comprising the VH CDRs of the VH of P1-068757 and a VL comprising the VL CDRs of P1-068757, 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 P1-068757;

[0239] (d) a VH comprising the VH CDRs of the VH of P1-068759 and a VL comprising the VL CDRs of P1-068759, 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 P1-068759;

[0240] (e) a VH comprising the VH CDRs of the VH of P1-068761 and a VL comprising the VL CDRs of P1-068761, 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;

[0241] (f) a VH comprising the VH CDRs of the VH of P1-068763 and a VL comprising the VL CDRs of P1-068763, 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 P1-068763;

[0242] (g) a VH comprising the VH CDRs of the VH of P1-068765 and a VL comprising the VL CDRs of P1-068765, 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 P1-068765;

[0243] (h) a VH comprising the VH CDRs of the VH of P1-068767 and a VL comprising the VL CDRs of P1-068767, 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;

[0244] (i) a VH comprising the VH CDRs of the VH of P1-068769 and 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;

[0245] (j) a VH comprising the VH CDRs of the VH of P1-068771 and a VL comprising the VL CDRs of P1-068771, 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 P1-068771;

[0246] (k) a VH comprising the VH CDRs of the VH of P1-068773 and a VL comprising the VL CDRs of P1-068773, 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 P1-068773;

[0247] (l) a VH comprising the VH CDRs of the VH of P1-068775 and a VL comprising the VL CDRs of P1-068775, 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 P1-068775;

[0248] (m) a VH comprising the VH CDRs of the VH of P1-069059 and a VL comprising the VL CDRs of P1-069059, 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 P1-069059;

[0249] (n) a VH comprising the VH CDRs of the VH of P1-069061 and a VL comprising the VL CDRs of P1-069061, 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 P1-069061;

[0250] (o) a VH comprising the VH CDRs of the VH of P1-069063 and a VL comprising the VL CDRs of P1-069063, 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 P1-069063;

[0251] (p) a VH comprising the VH CDRs of the VH of P1-069065 and a VL comprising the VL CDRs of P1-069065, 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 P1-069065;

[0252] (q) a VH comprising the VH CDRs of the VH of P1-069067 and a VL comprising the VL CDRs of P1-069067, 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 P1-069067;

[0253] (r) a VH comprising the VH CDRs of the VH of P1-069069 and a VL comprising the VL CDRs of P1-069069, 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 P1-069069;

[0254] (s) a VH comprising the VH CDRs of the VH of P1-069071 and 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;

[0255] (t) a VH comprising the VH CDRs of the VH of P1-069073 and a VL comprising the VL CDRs of P1-069073, 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 P1-069073;

[0256] (u) a VH comprising the VH CDRs of the VH of P1-069075 and a VL comprising the VL CDRs of P1-069075, 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 P1-069075;

[0257] (v) a VH comprising the VH CDRs of the VH of P1-069077 and 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;

[0258] (w) a VH comprising the VH CDRs of the VH of P1-068736 and a VL comprising the VL CDRs of P1-068736, 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 P1-068736;

[0259] (x) a VH comprising the VH CDRs of the VH of P1-068738 and 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;

[0260] (y) a VH comprising the VH CDRs of the VH of P1-068740 and a VL comprising the VL CDRs of P1-068740, 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 P1-068740;

[0261] (z) a VH comprising the VH CDRs of the VH of P1-068742 and a VL comprising the VL CDRs of P1-068742, 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 P1-068742;

[0262] (aa) a VH comprising the VH CDRs of the VH of P1-068744, and a VL comprising the VL CDRs of P1-068744, 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 P1-068744;

[0263] (bb) a VH comprising the VH CDRs of the VH of P1-068746 and a VL comprising the VL CDRs of P1-068746, 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 P1-068746;

[0264] (cc) a VH comprising the VH CDRs of the VH of P1-068748 and 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;

[0265] (dd) a VH comprising the VH CDRs of the VH of P1-068750 and a VL comprising the VL CDRs of P1-068750, 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 P1-068750;

[0266] (ee) a VH comprising the VH CDRs of the VH of P1-068752 and 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;

[0267] (ff) a VH comprising the VH CDRs of the VH of P1-068754, and 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;

[0268] (gg) a VH comprising the VH CDRs of the VH of P1-068761_E55A, and 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;

[0269] (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;

[0270] (ii) a VH comprising the VH CDRs of the VH of P1-068761_E56N and 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;

[0271] (jj) a VH comprising the VH CDRs of the VH of P1-068761_E55A_E56N, and 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;

[0272] (kk) a VH comprising the VH CDRs of the VH of P1-068761_E30D, and 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;

[0273] (ll) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E55A and 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;

[0274] (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;

[0275] (nn) a VH comprising the VH CDRs of the VH of P1-068761_E30D_H100G, and 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;

[0276] (oo) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E56N, and 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;

[0277] (pp) a VH comprising the VH CDRs of the VH of P1-068761_E100fF, and a VL comprising the VLCDRs 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;

[0278] (qq) a VH comprising the VH CDRs of the VH of P1-068761_E55A_E100fF, and 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;

[0279] (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 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_E100fF;

[0280] (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;

[0281] (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 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_E100fF;

[0282] (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;

[0283] (vv) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_E55A, and a VL comprising the VL CDRs of P1-068761_E32Y_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_E32Y_E55A;

[0284] (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;

[0285] (xx) a VH comprising the VH CDRs of the VH of P1-068761_E30D_E32Y and 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;

[0286] (yy) a VH comprising the VH CDRs of the VH of P1-068761_E32Y_H100G, and 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;

[0287] (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;

[0288] (aaa) a VH comprising the VH CDRs of the VH of P1-068767_D52N_D102V, and 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;

[0289] (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;

[0290] (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;

[0291] (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;

[0292] (eee) a VH comprising the VH CDRs of the VH of P1-068767_D102V, and 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;

[0293] (fff) a VH comprising the VH CDRs of the VH of P1-068767_E55A, and 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;

[0294] (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;

[0295] (hhh) a VH comprising the VH CDRs of the VH of P1-068767_E30D_D102V, and 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;

[0296] (iii) a VH comprising the VH CDRs of the VH of P1-068767_E30D and 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;

[0297] (jjj) a VH comprising the VH CDRs of the VH of P1-068767_E30D_E55A, and 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;

[0298] (kkk) a VH comprising the VH CDRs of the VH of P1-068767_E100fF_D102V, a VL comprising the VL CDRs 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;

[0299] (lll) a VH comprising the VH CDRs of the VH of P1-068767_E55A_E100fF, and 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;

[0300] (mmm) a VH comprising the VH CDRs of the VH of P1-068767_D52N_E100fF, and 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;

[0301] (nnn) a VH comprising the VH CDRs of the VH of P1-068767_E100fF, and a VL comprising the VLCDRs of P1-068767_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_E100fF; or

[0302] (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. The anti-hVISTA Ab may comprise:

[0303] (a) VH consisting of the amino acid sequence of VH of P1-061029 and VL consisting of VL of P1-061029;

[0304] (b) a VH consisting of the amino acid sequence of VH of P1-061015 and a VL consisting of VL of P1-061015;

[0305] (c) a VH consisting of the amino acid sequence of VH of P1-068757 and a VL consisting of VL of P1-068757;

[0306] (d) a VH consisting of the amino acid sequence of VH of P1-068759 and a VL consisting of VL of P1-068759;

[0307] (e) a VH consisting of the amino acid sequence of VH of P1-068761 and a VL consisting of VL of P1-068761;

[0308] (f) a VH consisting of the amino acid sequence of VH of P1-068763 and a VL consisting of VL of P1-068763;

[0309] (g) a VH consisting of the amino acid sequence of VH of P1-068765 and a VL consisting of VL of P1-068765;

[0310] (h) a VH consisting of the amino acid sequence of VH of P1-068767 and a VL consisting of VL of P1-068767;

[0311] (i) a VH consisting of the amino acid sequence of VH of P1-068769 and a VL consisting of VL of P1-068769;

[0312] (j) a VH consisting of the amino acid sequence of VH of P1-068771 and a VL consisting of VL of P1-068771;

[0313] (k) a VH consisting of the amino acid sequence of VH of P1-068773 and a VL consisting of VL of P1-068773;

[0314] (1) a VH consisting of the amino acid sequence of VH of P1-068775 and a VL consisting of VL of P1-068775;

[0315] (m) a VH consisting of the amino acid sequence of VH of P1-069059 and a VL consisting of VL of P1-069059;

[0316] (n) a VH consisting of the amino acid sequence of VH of P1-069061 and a VL consisting of VL of P1-069061;

[0317] (o) a VH consisting of the amino acid sequence of VH of P1-069063 and a VL consisting of VL of P1-069063;

[0318] (p) a VH consisting of the amino acid sequence of VH of P1-069065 and a VL consisting of VL of P1-069065;

[0319] (q) a VH consisting of the amino acid sequence of VH of P1-069067 and a VL consisting of VL of P1-069067;

[0320] (r) a VH consisting of the amino acid sequence of VH of P1-069069 and a VL consisting of VL of P1-069069;

[0321] (s) VH consisting of the amino acid sequence of VH of P1-069071 and VL consisting of VL of P1-069071;

[0322] (t) a VH consisting of the amino acid sequence of VH of P1-069073 and a VL consisting of VL of P1-069073;

[0323] (u) a VH consisting of the amino acid sequence of VH of P1-069075 and a VL consisting of VL of P1-069075;

[0324] (v) a VH consisting of the amino acid sequence of VH of P1-069077 and a VL consisting of VL of P1-069077;

[0325] (w) a VH consisting of the amino acid sequence of VH of P1-068736 and a VL consisting of VL of P1-068736;

[0326] (x) a VH consisting of the amino acid sequence of VH of P1-068738 and a VL consisting of VL of P1-068738;

[0327] (y) a VH consisting of the amino acid sequence of VH of P1-068740 and a VL consisting of VL of P1-068740;

[0328] (z) a VH consisting of the amino acid sequence of VH of P1-068742 and a VL consisting of VL of P1-068742;

[0329] (aa) VH consisting of the amino acid sequence of VH of P1-068744 and VL consisting of VL of P1-068744;

[0330] (bb) a VH consisting of the amino acid sequence of VH of P1-068746 and a VL consisting of VL of P1-068746;

[0331] (cc) a VH consisting of the amino acid sequence of VH of P1-068748 and a VL consisting of VL of P1-068748;

[0332] (dd) a VH consisting of the amino acid sequence of the VH of P1-068750 and a VL consisting of the VL of P1-068750;

[0333] (ee) a VH consisting of the amino acid sequence of VH of P1-068752 and a VL consisting of VL of P1-068752;

[0334] (ff) a VH consisting of the amino acid sequence of VH of P1-068754 and a VL consisting of VL of P1-068754;

[0335] (gg) a VH consisting of the amino acid sequence of the VH of P1-068761_E55A and a VL consisting of the amino acid sequence of the VL of P1-068761_E55A;

[0336] (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;

[0337] (ii) a VH consisting of the amino acid sequence of VH of P1-068761_E56N and a VL consisting of the amino acid sequence of VL of P1-068761_E56N;

[0338] (jj) a VH consisting of the amino acid sequence of VH of P1-068761_E55A_E56N and a VL consisting of the amino acid sequence of VL of P1-068761_E55A_E56N;

[0339] (kk) a VH consisting of the amino acid sequence of VH of P1-068761_E30D and a VL consisting of the amino acid sequence of VL of P1-068761_E30D;

[0340] (11) a VH consisting of the amino acid sequence of VH of P1-068761_E30D_E55A and a VL consisting of the amino acid sequence of VL of P1-068761_E30D_E55A;

[0341] (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;

[0342] (nn) a VH consisting of the amino acid sequence of VH of P1-068761_E30D_H100G and a VL consisting of the amino acid sequence of VL of P1-068761_E30D_H100G;

[0343] (oo) a VH consisting of the amino acid sequence of the VH of P1-068761_E30D_E56N and a VL consisting of the amino acid sequence of the VL of P1-068761_E30D_E56N;

[0344] (pp) a VH consisting of the amino acid sequence of VH of P1-068761_E100fF and a VL consisting of the amino acid sequence of VL of P1-068761_E100fF;

[0345] (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;

[0346] (rr) a VH consisting of the amino acid sequence of the VH of P1-068761_H100G_E100fF and a VL consisting of the amino acid sequence of the VL of P1-068761_H100G_E100fF;

[0347] (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;

[0348] (tt) a VH consisting of the amino acid sequence of VH of P1-068761_E56N_E100fF and a VL consisting of the amino acid sequence of VL of P1-068761_E56N_E100fF;

[0349] (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;

[0350] (vv) a VH consisting of the amino acid sequence of VH of P1-068761_E32Y_E55A and a VL consisting of the amino acid sequence of VL of P1-068761_E32Y_E55A;

[0351] (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;

[0352] (xx) a VH consisting of the amino acid sequence of VH of P1-068761_E30D_E32Y and a VL consisting of the amino acid sequence of VL of P1-068761_E30D_E32Y;

[0353] (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;

[0354] (zz) a VH consisting of the amino acid sequence of the VH of P1-068761_E32Y_E100fF and a VL consisting of the amino acid sequence of the VL of P1-068761_E32Y_E100fF;

[0355] (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;

[0356] (bbb) a VH consisting of the amino acid sequence of the VH of P1-068767_D52N and a VL consisting of the amino acid sequence of the VL of P1-068767_D52N;

[0357] (ccc) a VH consisting of the amino acid sequence of the VH of P1-068767_D52N_E55A and a VL consisting of the amino acid sequence of the VL of P1-068767_D52N_E55A;

[0358] (ddd) a VH consisting of the amino acid sequence of the VH of P1-068767_E55A_D102V and a VL consisting of the amino acid sequence of the VL of P1-068767_E55A_D102V;

[0359] (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;

[0360] (fff) a VH consisting of the amino acid sequence of VH of P1-068767_E55A and a VL consisting of the amino acid sequence of VL of P1-068767_E55A;

[0361] (ggg) a VH consisting of the amino acid sequence of the VH of P1-068767_E30D_D52N and a VL consisting of the amino acid sequence of the VL of P1-068767_E30D_D52N;

[0362] (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;

[0363] (iii) a VH consisting of the amino acid sequence of VH of P1-068767_E30D and a VL consisting of the amino acid sequence of VL of P1-068767_E30D;

[0364] (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;

[0365] (kkk) a VH consisting of the amino acid sequence of VH of P1-068767_E100fF_D102V and a VL consisting of the amino acid sequence of VL of P1-068767_E100fF_D102V;

[0366] (111) a VH consisting of the amino acid sequence of VH of P1-068767_E55A_E100fF and a VL consisting of the amino acid sequence of VL of P1-068767_E55A_E100fF;

[0367] (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;

[0368] (nnn) a VH consisting of the amino acid sequence of VH of P1-068767_E100fF and a VL consisting of the amino acid sequence of VL of P1-068767_E100fF; or

[0369] (ooo) a VH consisting of the amino acid sequence of the VH of P1-068767_E30D_E100fF and a VL consisting of the amino acid sequence of the VL of P1-068767_E30D_E100fF. In certain embodiments, the anti-VISTAAb comprises any variable region and / or variable region CDR 1-3 of the following antibodies described above and elsewhere herein, such as:

[0370] (1) one or more of the VH CDR1, CDR2, and CDR3 of the following antibody:

[0371] (2) VH CDR1, CDR2 and CDR3 of the following antibodies:

[0372] (3) VH of the following antibodies:

[0373] (4) VH CDR1, CDR2 and CDR3 and VL CDR1, CDR2 and CDR3 of the following antibody:

[0374] (5) VH CDR1, CDR2 and CDR3 and VL CDR1, CDR2 and CDR3 of the following antibody: or

[0375] (6) VH and VL of the following antibodies:

[0376] P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1 -068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-0 69061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069 073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740 , P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P 1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-0687 61_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N _H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100f F. P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_ E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55 A. P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, 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, P1-068767_E30D_D102V, P1-068767_E30D, P 1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF;and anti-VISTAAb;

[0377] It is also an IgG antibody (such as an IgG1, IgG2, IgG3 or IgG4 antibody) or a modified form thereof as described in the following sections. In some embodiments, the constant region has effector function, and in some embodiments, the constant region has no effector. In certain embodiments, the constant region is the constant region of IgG1.3.

[0378] In certain embodiments, the anti-VISTA Ab comprises any of the variable regions and / or variable region CDRs 1-3 of the following antibodies described above and elsewhere herein, such as:

[0379] (1) one or more of the VH CDR1, CDR2, and CDR3 of the following antibody:

[0380] (2) VH CDR1, CDR2 and CDR3 of the following antibodies:

[0381] (3) VH of the following antibodies:

[0382] (4) VH CDR1, CDR2 and CDR3 and VL CDR1, CDR2 and CDR3 of the following antibody:

[0383] (5) VH CDR1, CDR2 and CDR3 and VL CDR1, CDR2 and CDR3 of the following antibody: or

[0384] (6) VH and VL of the following antibodies:

[0385] P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1 -068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-0 69061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069 073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740 , P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752, P 1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-0687 61_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N _H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100f F. P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_ E100fF, P1-068761_E56N_E100fF, P1-068761_E32Y, P1-068761_E32Y_E55 A. P1-068761_E32Y_E56N, P1-068761_E30D_E32Y, 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, P1-068767_E30D_D102V, P1-068767_E30D, P 1-068767_E30D_E55A, P1-068767_E100fF_D102V, P1-068767_E55A_E100fF, P1-068767_D52N_E100fF, P1-068767_E100fF, or P1-068767_E30D_E100fF,

[0386] and further include one or more of the following features:

[0387] - specifically binds to hVISTA (e.g., the ECD or a histidine-rich region of a polypeptide comprising amino acid residues 35-127 of SEQ ID NO: 2) at acidic pH (e.g., pH 6.0 or pH 6.5);

[0388] - lack of significant binding to hVISTA (e.g., the ECD or the histidine-rich region of a polypeptide comprising amino acid residues 35-127 of SEQ ID NO: 2) at physiological pH or neutral pH (e.g., pH 7.4 or pH 7.0);

[0389] - specifically binds to cyno VISTA (e.g., the histidine-rich region of the ECD) at acidic pH (e.g., pH 6.0 or pH 6.5);

[0390] - lack of significant binding to cyno VISTA (e.g., the histidine-rich region of the ECD) at physiological or neutral pH (e.g., pH 7.4 or pH 7.0);

[0391] - has reduced binding to hVISTA-ECD with substitutions at one or more of the following amino acids relative to hVISTA ECD having SEQ ID NO: 2: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127;

[0392] - Cross-competes with P1-061029, P1-068761, P1-068767, and / or P1-061015 for binding to hVISTA;

[0393] - Inhibits hVISTA binding to human T cells at acidic pH (e.g., pH 6.0 or pH 6.5);

[0394] - Inhibits the binding of hVISTA to PSGL-1 at acidic pH (e.g., pH 6.0 or pH 6.5);

[0395] - Mean residence time in cynomolgus monkeys of at least 350 hours;

[0396] - Stimulate T cell activation;

[0397] - Inhibition of VISTA-mediated cell:cell adhesion; and

[0398] -Specifically binds to hVISTA in samples of human tumor cells or inflamed human tissue.

[0399] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain (HC) comprising the amino acid sequence of the heavy chain of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises P1-061029 or P1-061015 or its progeny such as P1-061029.IgG1.3 (SEQ ID NO: 1061029-1061015) comprising an IgG1.3 heavy chain constant region as shown in the following sequence table. NO:69), P1-068757.IgG1.3, P1-068759.IgG1.3, P1-068761.IgG1.3, P1-068763.IgG1.3, P1-068765.IgG1.3, P1-068767.IgG 1.3, 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.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, P1-06 8742.IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1.3, P1-068752.IgG1.3, P1-06875 4.IgG1.3, P1-068761_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.IgG 1.3, P1-068761_E32Y_E55A.IgG1.3, P1-068761_E32Y_E56N.IgG1.3, P1-068761_E30D_E32Y. IgG1.3, P1-068761_E32Y_H100G.IgG1.3, P1-068761_E32Y_E100fF.IgG1.3, P1-068767_D52N _D102V.IgG1.3, P1-068767_D52N.IgG1.3, P1-068767_D52N_E55A.IgG1.3, P1-068767_E55A_D 102V.IgG1.3, P1-068767_D102V.IgG1.3, P1-068767_E55A.IgG1.3, P1-068767_E30D_D52N.I gG1.3, P1-068767_E30D_D102V.IgG1.3, P1-068767_E30D.IgG1.3, P1-068767_E30D_E55A.IgG 1.3, P1-068767_E100fF_D102V.IgG1.3, P1-068767_E55A_E100fF.IgG1.3, P1-068767_D52N_E100fF.IgG1.3, P1-068767_E100fF.IgG1.3 or P1-068767_E30D_E100fF.IgG1.3.

[0400] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain comprising the amino acid sequence of a heavy chain of any anti-hVISTA Ab provided herein (which comprises an IgG1.3 heavy chain constant region) and the amino acid sequence of a light chain of any anti-hVISTA Ab provided herein. In certain embodiments, the anti-hVISTA Ab comprises an amino acid sequence of a light chain comprising P1-061029 or P1-061015 or progeny thereof (which comprise an IgG1.3 HC constant region) such as 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, P1-06906 1.IgG1.3, P1-069063.IgG1.3, P1-069065.IgG1.3, P1-069067.IgG1.3, P1-069069.IgG1.3, P1-069071.IgG1.3, P1-0690 73.IgG1.3, P1-069075.IgG1.3, P1-069077.IgG1.3, P1-061015.IgG1.3, P1-068736.IgG1.3, P1-068738.IgG1.3, P1-0687 40.IgG1.3, P1-068742.IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1.3, P1-068 752.IgG1.3, P1-068754.IgG1.3, P1-068761_E55A.IgG1.3, P1-068761_H100G.IgG1.3, P1-068761_E56N.IgG1.3, P1-0687 61_E55A_E56N.IgG1.3, P1-068761_E30D.IgG1.3, P1-068761_E30D_E55A.IgG1.3, P1-068761_E56N_H100G.IgG1.3, P1-0 68761_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.IgG 1.3, P1-068761_E32Y.IgG1.3, P1-068761_E32Y_E55A.IgG1.3, P1-068761_E32Y_E56N.IgG1.3, P1-0687 61_E30D_E32Y.IgG1.3, P1-068761_E32Y_H100G.IgG1.3, P1-068761_E32Y_E100fF.IgG1.3, P1-068767 _D52N_D102V.IgG1.3, P1-068767_D52N.IgG1.3, P1-068767_D52N_E55A.IgG1.3, P1-068767_E55A_D102 V.IgG1.3, P1-068767_D102V.IgG1.3, P1-068767_E55A.IgG1.3, P1-068767_E30D_D52N.IgG1.3, P1-06 8767_E30D_D102V.IgG1.3, P1-068767_E30D.IgG1.3, P1-068767_E30D_E55A.IgG1.3, P1-068767_E100f F_D102V.IgG1.3, P1-068767_E55A_E100fF.IgG1.3, P1-068767_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.

[0401] Anti-hVISTA Abs may contain:

[0402] (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);

[0403] (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;

[0404] (c) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068757.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068757;

[0405] (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;

[0406] (e) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068761;

[0407] (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;

[0408] (g) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068765.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068765;

[0409] (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;

[0410] (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;

[0411] (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;

[0412] (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;

[0413] (l) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068775.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068775;

[0414] (m) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069059.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069059;

[0415] (n) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069061.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069061;

[0416] (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;

[0417] (p) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069065.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069065;

[0418] (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;

[0419] (r) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069069.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069069;

[0420] (s) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069071.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069071;

[0421] (t) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069073.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069073;

[0422] (u) a heavy chain comprising the amino acid sequence of the heavy chain of P1-069075.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-069075;

[0423] (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;

[0424] (w) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068736.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068736;

[0425] (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;

[0426] (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;

[0427] (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;

[0428] (aa) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068744.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068744;

[0429] (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;

[0430] (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;

[0431] (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;

[0432] (ee) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068752.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068752;

[0433] (ff) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068754.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068754;

[0434] (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 light chain amino acid sequence of P1-068761_E55A;

[0435] (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 light chain amino acid sequence of P1-068761_H100G;

[0436] (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 light chain amino acid sequence of P1-068761_E56N;

[0437] (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 light chain amino acid sequence of P1-068761_E55A_E56N;

[0438] (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;

[0439] (11) 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 light chain amino acid sequence of P1-068761_E30D_E55A;

[0440] (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 light chain amino acid sequence of P1-068761_E56N_H100G;

[0441] (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 light chain amino acid sequence of P1-068761_E30D_H100G;

[0442] (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 light chain amino acid sequence of P1-068761_E30D_E56N;

[0443] (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 light chain amino acid sequence of P1-068761_E100fF;

[0444] (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 light chain amino acid sequence of P1-068761_E55A_E100fF;

[0445] (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 light chain amino acid sequence of P1-068761_H100G_E100fF;

[0446] (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 light chain amino acid sequence of P1-068761_E30D_E100fF;

[0447] (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 light chain amino acid sequence of P1-068761_E56N_E100fF;

[0448] (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 light chain amino acid sequence of P1-068761_E32Y;

[0449] (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 light chain amino acid sequence of P1-068761_E32Y_E55A;

[0450] (ww) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_E56N.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068761_E32Y_E56N;

[0451] (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 light chain amino acid sequence of P1-068761_E30D_E32Y;

[0452] (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 light chain amino acid sequence of P1-068761_E32Y_H100G;

[0453] (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 light chain amino acid sequence of P1-068761_E32Y_E100fF;

[0454] (aaa) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N_D102V.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068767_D52N_D102V;

[0455] (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 light chain amino acid sequence of P1-068767_D52N;

[0456] (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 light chain amino acid sequence of P1-068767_D52N_E55A;

[0457] (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 light chain amino acid sequence of P1-068767_E55A_D102V;

[0458] (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 light chain amino acid sequence of P1-068767_D102V;

[0459] (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 light chain amino acid sequence of P1-068767_E55A;

[0460] (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 light chain amino acid sequence of P1-068767_E30D_D52N;

[0461] (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 light chain amino acid sequence of P1-068767_E30D_D102V;

[0462] (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 light chain amino acid sequence of P1-068767_E30D;

[0463] (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 light chain amino acid sequence of P1-068767_E30D_E55A;

[0464] (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 light chain amino acid sequence of P1-068767_E100fF_D102V;

[0465] (111) 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 light chain amino acid sequence of P1-068767_E55A_E100fF;

[0466] (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 light chain amino acid sequence of P1-068767_D52N_E100fF;

[0467] (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 light chain amino acid sequence of P1-068767_E100fF; or

[0468] (ooo) a heavy chain containing the amino acid sequence of the heavy chain of P1-068767_E30D_E100fF.IgG1.3 and a light chain containing the light chain amino acid sequence of P1-068767_E30D_E100fF. Anti-hVISTA Ab may comprise:

[0469] (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;

[0470] (b) a HC comprising the HC CDRs of the HC of P1-061015 and a LC comprising the LC CDRs of P1-061015, 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 P1-061015.IgG1.3, respectively;

[0471] (c) a HC comprising the HC CDRs of the HC of P1-068757 and a LC comprising the LC CDRs of P1-068757, 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 P1-068757.IgG1.3, respectively;

[0472] (d) a HC comprising the HC CDRs of the HC of P1-068759 and a LC comprising the LC CDRs of P1-068759, 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 P1-068759.IgG1.3, respectively;

[0473] (e) a HC comprising the HC CDRs of the HC of P1-068761 and a LC comprising the LC CDRs of P1-068761, 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.IgG1.3, respectively;

[0474] (f) a HC comprising the HC CDRs of the HC of P1-068763 and a LC comprising the LC CDRs of P1-068763, 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 P1-068763.IgG1.3, respectively;

[0475] (g) a HC comprising the HC CDRs of the HC of P1-068765 and a LC comprising the LC CDRs of P1-068765, 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 P1-068765.IgG1.3, respectively;

[0476] (h) a HC comprising the HC CDRs of the HC of P1-068767 and a LC comprising the LC CDRs of P1-068767, 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.IgG1.3, respectively;

[0477] (i) a HC comprising the HC CDRs of the HC of P1-068769 and a LC comprising the LC CDRs of P1-068769, 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 P1-068769.IgG1.3, respectively;

[0478] (j) a HC comprising the HC CDRs of the HC of P1-068771 and a LC comprising the LC CDRs of P1-068771, 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 P1-068771.IgG1.3, respectively;

[0479] (k) a HC comprising the HC CDRs of the HC of P1-068773 and a LC comprising the LC CDRs of P1-068773, 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 P1-068773.IgG1.3, respectively;

[0480] (l) a HC comprising the HC CDRs of the HC of P1-068775 and a LC comprising the LC CDRs of P1-068775, 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 P1-068775.IgG1.3, respectively;

[0481] (m) a HC comprising the HC CDRs of the HC of P1-069059 and a LC comprising the LC CDRs of P1-069059, 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 P1-069059.IgG1.3, respectively;

[0482] (n) a HC comprising the HC CDRs of the HC of P1-069061 and a LC comprising the LC CDRs of P1-069061, 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 P1-069061.IgG1.3, respectively;

[0483] (o) a HC comprising the HC CDRs of the HC of P1-069063 and a LC comprising the LC CDRs of P1-069063, 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 P1-069063.IgG1.3, respectively;

[0484] (p) a HC comprising the HC CDRs of the HC of P1-069065 and a LC comprising the LC CDRs of P1-069065, 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 P1-069065.IgG1.3, respectively;

[0485] (q) a HC comprising the HC CDRs of the HC of P1-069067 and a LC comprising the LC CDRs of P1-069067, 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 P1-069067.IgG1.3, respectively;

[0486] (r) a HC comprising the HC CDRs of the HC of P1-069069 and a LC comprising the LC CDRs of P1-069069, 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 P1-069069.IgG1.3, respectively;

[0487] (s) a HC comprising the HC CDRs of the HC of P1-069071 and a LC comprising the LC CDRs of P1-069071, 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 P1-069071.IgG1.3, respectively;

[0488] (t) a HC comprising the HC CDRs of the HC of P1-069073 and a LC comprising the LC CDRs of P1-069073, 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 P1-069073.IgG1.3, respectively;

[0489] (u) a HC comprising the HC CDRs of the HC of P1-069075 and a LC comprising the LC CDRs of P1-069075, 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 P1-069075.IgG1.3, respectively;

[0490] (v) a HC comprising the HC CDRs of the HC of P1-069077 and a LC comprising the LC CDRs of P1-069077, 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 P1-069077.IgG1.3, respectively;

[0491] (w) a HC comprising the HC CDRs of the HC of P1-068736 and a LC comprising the LC CDRs of P1-068736, 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 P1-068736.IgG1.3, respectively;

[0492] (x) a HC comprising the HC CDRs of the HC of P1-068738 and a LC comprising the LC CDRs of P1-068738, 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 P1-068738.IgG1.3, respectively;

[0493] (y) a HC comprising the HC CDRs of the HC of P1-068740 and a LC comprising the LC CDRs of P1-068740, 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 P1-068740.IgG1.3, respectively;

[0494] (z) a HC comprising the HC CDRs of the HC of P1-068742 and a LC comprising the LC CDRs of P1-068742, 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 P1-068742.IgG1.3, respectively;

[0495] (aa) a HC comprising the HC CDRs of the HC of P1-068744, and a LC comprising the LC CDRs of P1-068744, 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 P1-068744.IgG1.3, respectively;

[0496] (bb) a HC comprising the HC CDRs of the HC of P1-068746 and a LC comprising the LC CDRs of P1-068746, 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 P1-068746.IgG1.3, respectively;

[0497] (cc) a HC comprising the HC CDRs of the HC of P1-068748 and a LC comprising the LC CDRs of P1-068748, 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 P1-068748.IgG1.3, respectively;

[0498] (dd) a HC comprising the HC CDRs of the HC of P1-068750, and a LC comprising the LC CDRs of P1-068750, 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 P1-068750.IgG1.3, respectively;

[0499] (ee) a HC comprising the HC CDRs of the HC of P1-068752 and a LC comprising the LC CDRs of P1-068752, 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 P1-068752.IgG1.3, respectively;

[0500] (ff) a HC comprising the HC CDRs of the HC of P1-068754 and a LC comprising the LC CDRs of P1-068754, 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 P1-068754.IgG1.3, respectively;

[0501] (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 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.IgG1.3, respectively;

[0502] (hh) 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 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_H100G.IgG1.3, respectively;

[0503] (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 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.IgG1.3, respectively;

[0504] (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;

[0505] (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 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.IgG1.3, respectively;

[0506] (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 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;

[0507] (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 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;

[0508] (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 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_H100G.IgG1.3, respectively;

[0509] (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 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;

[0510] (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;

[0511] (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 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;

[0512] (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 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_H100G_E100fF.IgG1.3, respectively;

[0513] (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 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_E100fF.IgG1.3, respectively;

[0514] (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;

[0515] (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 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.IgG1.3, respectively;

[0516] (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 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;

[0517] (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;

[0518] (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 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_E32Y.IgG1.3, respectively;

[0519] (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;

[0520] (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 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_E100fF.IgG1.3, respectively;

[0521] (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 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_D102V.IgG1.3, respectively;

[0522] (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;

[0523] (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 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;

[0524] (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;

[0525] (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 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;

[0526] (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 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;

[0527] (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;

[0528] (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 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;

[0529] (iii) 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 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.IgG1.3, respectively;

[0530] (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;

[0531] (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;

[0532] (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 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_E100fF.IgG1.3, respectively;

[0533] (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;

[0534] (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 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.IgG1.3, respectively; or

[0535] (ooo) a HC containing the HC CDRs of the HC of P1-068767_E30D_E100fF.IgG1.3 and a LC containing the LC CDRs of P1-068767_E30D_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_E30D_E100fF.IgG1.3, respectively. In some embodiments, the anti-hVISTA Ab may comprise:

[0536] (a) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-061029.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-061029;

[0537] (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;

[0538] (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;

[0539] (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;

[0540] (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;

[0541] (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;

[0542] (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;

[0543] (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;

[0544] (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;

[0545] (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;

[0546] (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;

[0547] (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;

[0548] (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;

[0549] (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;

[0550] (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;

[0551] (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;

[0552] (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;

[0553] (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;

[0554] (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;

[0555] (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;

[0556] (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;

[0557] (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;

[0558] (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;

[0559] (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;

[0560] (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;

[0561] (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;

[0562] (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;

[0563] (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;

[0564] (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;

[0565] (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;

[0566] (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;

[0567] (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;

[0568] (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;

[0569] (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;

[0570] (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;

[0571] (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;

[0572] (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;

[0573] (11) 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;

[0574] (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;

[0575] (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;

[0576] (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;

[0577] (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;

[0578] (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;

[0579] (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;

[0580] (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;

[0581] (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;

[0582] (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;

[0583] (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;

[0584] (ww) a heavy chain consisting of the amino acid sequence of the heavy chain of 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;

[0585] (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;

[0586] (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;

[0587] (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;

[0588] (aaa) a heavy chain consisting of the amino acid sequence of the heavy chain of 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;

[0589] (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;

[0590] (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;

[0591] (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;

[0592] (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;

[0593] (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;

[0594] (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;

[0595] (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;

[0596] (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;

[0597] (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;

[0598] (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;

[0599] (111) 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;

[0600] (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;

[0601] (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

[0602] (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.

[0603] In some embodiments, the present disclosure contemplates an anti-VISTA mAb comprising:

[0604] a heavy chain consisting of the amino acid sequence of a heavy chain as listed above from (a) to (ooo) followed by a Lys residue; and

[0605] A light chain consisting of the light chain amino acid sequence of (a) to (ooo) listed above;

[0606] wherein the heavy chain and light chain amino acid sequences are selected from the same antibody class from (a) to (ooo) listed above.

[0607] In some embodiments, an anti-hVISTA Ab may comprise a VH amino acid sequence comprising an antibody species herein, but not a heavy chain amino acid sequence of an IgG1.3 heavy chain constant region, as provided in the HC sequence in the sequence listing herein (and see SEQ ID NO: 163), and 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)). Accordingly, embodiments of the present disclosure include an anti-VISTA Ab comprising:

[0608] (a) a heavy chain comprising (i) the amino acid sequence of 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);

[0609] (b) a heavy chain comprising (i) the amino acid sequence of 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;

[0610] (c) a heavy chain comprising (i) the amino acid sequence of 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;

[0611] (d) a heavy chain comprising (i) the amino acid sequence of 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;

[0612] (e) a heavy chain comprising (i) the amino acid sequence of 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;

[0613] (f) a heavy chain comprising (i) the amino acid sequence of 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;

[0614] (g) a heavy chain comprising (i) the amino acid sequence of 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;

[0615] (h) a heavy chain comprising (i) the amino acid sequence of 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;

[0616] (i) a heavy chain comprising (i) the amino acid sequence of 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;

[0617] (j) a heavy chain comprising (i) the amino acid sequence of 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;

[0618] (k) a heavy chain comprising (i) the amino acid sequence of 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;

[0619] (1) a heavy chain comprising (i) the amino acid sequence of 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;

[0620] (m) a heavy chain comprising (i) the amino acid sequence of 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;

[0621] (n) a heavy chain comprising (i) the amino acid sequence of 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;

[0622] (o) a heavy chain comprising (i) the amino acid sequence of 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;

[0623] (p) a heavy chain comprising (i) the amino acid sequence of 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;

[0624] (q) a heavy chain comprising (i) the amino acid sequence of 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;

[0625] (r) a heavy chain comprising (i) the amino acid sequence of 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;

[0626] (s) a heavy chain comprising (i) the amino acid sequence of 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;

[0627] (t) a heavy chain comprising (i) the amino acid sequence of 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;

[0628] (u) a heavy chain comprising (i) the amino acid sequence of 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;

[0629] (v) a heavy chain comprising (i) the amino acid sequence of 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;

[0630] (w) a heavy chain comprising (i) the amino acid sequence of 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;

[0631] (x) a heavy chain comprising (i) the amino acid sequence of 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;

[0632] (y) a heavy chain comprising (i) the amino acid sequence of 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;

[0633] (z) a heavy chain comprising (i) the amino acid sequence of 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;

[0634] (aa) a heavy chain comprising (i) the amino acid sequence of 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;

[0635] (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;

[0636] (cc) a heavy chain comprising (i) the amino acid sequence of 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;

[0637] (dd) a heavy chain comprising (i) the amino acid sequence of 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;

[0638] (ee) a heavy chain comprising (i) the amino acid sequence of 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;

[0639] (ff) a heavy chain comprising (i) the amino acid sequence of 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;

[0640] (gg) a heavy chain comprising (i) the amino acid sequence of 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;

[0641] (hh) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_H100G;

[0642] (ii) a heavy chain comprising the amino acid sequence of (i) 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;

[0643] (jj) a heavy chain comprising the amino acid sequence of (i) 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;

[0644] (kk) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_E30D;

[0645] (ll) a heavy chain comprising the amino acid sequence of (i) 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;

[0646] (mm) a heavy chain comprising (i) the amino acid sequence of 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;

[0647] (nn) a heavy chain comprising the amino acid sequence of (i) 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;

[0648] (oo) a heavy chain comprising the amino acid sequence of (i) 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;

[0649] (pp) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_E100fF;

[0650] (qq) a heavy chain comprising the amino acid sequence of (i) 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;

[0651] (rr) a heavy chain comprising the amino acid sequence of (i) 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;

[0652] (ss) a heavy chain comprising the amino acid sequence of (i) 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;

[0653] (tt) a heavy chain comprising the amino acid sequence of (i) 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;

[0654] (uu) a heavy chain comprising the amino acid sequence of (i) 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;

[0655] (vv) a heavy chain comprising the amino acid sequence of (i) 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;

[0656] (ww) a heavy chain comprising the amino acid sequence of (i) 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;

[0657] (xx) a heavy chain comprising the amino acid sequence of (i) 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;

[0658] (yy) a heavy chain comprising the amino acid sequence of (i) 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;

[0659] (zz) a heavy chain comprising the amino acid sequence of (i) 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;

[0660] (aaa) a heavy chain comprising the amino acid sequence of (i) 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;

[0661] (bbb) a heavy chain comprising (i) 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;

[0662] (ccc) a heavy chain comprising the amino acid sequence of (i) 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;

[0663] (ddd) a heavy chain comprising the amino acid sequence of (i) 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;

[0664] (eee) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_D102V;

[0665] (fff) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E55A;

[0666] (ggg) a heavy chain comprising the amino acid sequence of (i) 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;

[0667] (hhh) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E30D_D102V;

[0668] (iii) a heavy chain comprising the amino acid sequence of (i) 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;

[0669] (jjj) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E30D_E55A;

[0670] (kkk) a heavy chain comprising the amino acid sequence of (i) 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;

[0671] (111) a heavy chain comprising the amino acid sequence of (i) 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;

[0672] (mmm) a heavy chain comprising the amino acid sequence of (i) 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;

[0673] (nnn) a heavy chain comprising the amino acid sequence of (i) 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

[0674] (ooo) a heavy chain comprising (i) 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.

[0675] Certain embodiments of the present disclosure include an anti-VISTA Ab comprising:

[0676] (a) a heavy chain consisting of (i) the VH amino acid sequence 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);

[0677] (b) a heavy chain consisting of (i) the amino acid sequence of 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;

[0678] (c) a heavy chain consisting of (i) the amino acid sequence of 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;

[0679] (d) a heavy chain consisting of (i) the amino acid sequence of 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;

[0680] (e) a heavy chain consisting of (i) the amino acid sequence of 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;

[0681] (f) a heavy chain consisting of (i) the amino acid sequence of 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;

[0682] (g) a heavy chain consisting of (i) the amino acid sequence of 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;

[0683] (h) a heavy chain consisting of (i) the amino acid sequence of 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;

[0684] (i) a heavy chain consisting of (i) the amino acid sequence of 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;

[0685] (j) a heavy chain consisting of (i) the amino acid sequence of 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;

[0686] (k) a heavy chain consisting of (i) the amino acid sequence of 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;

[0687] (l) a heavy chain consisting of (i) the amino acid sequence of 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;

[0688] (m) a heavy chain consisting of (i) the amino acid sequence of 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;

[0689] (n) a heavy chain consisting of (i) the amino acid sequence of 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;

[0690] (o) a heavy chain consisting of (i) the amino acid sequence of 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;

[0691] (p) a heavy chain consisting of (i) the amino acid sequence of 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;

[0692] (q) a heavy chain consisting of (i) the amino acid sequence of 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;

[0693] (r) a heavy chain consisting of (i) the amino acid sequence of 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;

[0694] (s) a heavy chain consisting of (i) the amino acid sequence of 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;

[0695] (t) a heavy chain consisting of (i) the amino acid sequence of 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;

[0696] (u) a heavy chain consisting of (i) the amino acid sequence of 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;

[0697] (v) a heavy chain consisting of (i) the amino acid sequence of 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;

[0698] (w) a heavy chain consisting of (i) the amino acid sequence of 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;

[0699] (x) a heavy chain consisting of (i) the amino acid sequence of 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;

[0700] (y) a heavy chain consisting of (i) the amino acid sequence of 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;

[0701] (z) a heavy chain consisting of (i) the amino acid sequence of 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;

[0702] (aa) a heavy chain consisting of (i) the amino acid sequence of 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;

[0703] (bb) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068746 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the light chain amino acid sequence of P1-068746;

[0704] (cc) a heavy chain consisting of (i) the amino acid sequence of 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;

[0705] (dd) a heavy chain consisting of (i) the amino acid sequence of 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;

[0706] (ee) a heavy chain consisting of (i) the amino acid sequence of 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;

[0707] (ff) a heavy chain consisting of (i) the amino acid sequence of 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;

[0708] (gg) a heavy chain consisting of (i) the amino acid sequence of 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;

[0709] (hh) a heavy chain consisting of (i) 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;

[0710] (ii) a heavy chain consisting of the amino acid sequence of (i) 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;

[0711] (jj) a heavy chain consisting of (i) the VH amino acid sequence 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;

[0712] (kk) a heavy chain consisting of (i) 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;

[0713] (ll) a heavy chain consisting of (i) the amino acid sequence of 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;

[0714] (mm) a heavy chain consisting of (i) the amino acid sequence of 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;

[0715] (nn) a heavy chain consisting of (i) the amino acid sequence of 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;

[0716] (oo) a heavy chain consisting of the amino acid sequence of (i) 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;

[0717] (pp) a heavy chain consisting of (i) 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;

[0718] (qq) a heavy chain consisting of (i) 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;

[0719] (rr) a heavy chain consisting of (i) 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;

[0720] (ss) a heavy chain consisting of (i) 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;

[0721] (tt) a heavy chain consisting of (i) 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;

[0722] (uu) a heavy chain consisting of (i) 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;

[0723] (vv) a heavy chain consisting of the amino acid sequence of (i) 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;

[0724] (ww) a heavy chain consisting of the amino acid sequence of (i) 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;

[0725] (xx) a heavy chain consisting of the amino acid sequence of (i) the 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;

[0726] (yy) a heavy chain consisting of (i) 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;

[0727] (zz) a heavy chain consisting of the amino acid sequence of (i) the 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;

[0728] (aaa) a heavy chain consisting of (i) 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;

[0729] (bbb) a heavy chain consisting of (i) the amino acid sequence of 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;

[0730] (ccc) a heavy chain consisting of (i) the amino acid sequence of 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;

[0731] (ddd) a heavy chain consisting of (i) 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;

[0732] (eee) a heavy chain consisting of (i) 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;

[0733] (fff) a heavy chain consisting of (i) 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;

[0734] (ggg) a heavy chain consisting of (i) the amino acid sequence of 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;

[0735] (hhh) a heavy chain consisting of (i) 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;

[0736] (iii) a heavy chain consisting of (i) the amino acid sequence of 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;

[0737] (jjj) a heavy chain consisting of (i) 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;

[0738] (kkk) a heavy chain consisting of (i) 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;

[0739] (lll) a heavy chain consisting of (i) the amino acid sequence of 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;

[0740] (mmm) a heavy chain consisting of (i) 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;

[0741] (nnn) a heavy chain consisting of (i) 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

[0742] (ooo) a heavy chain consisting of (i) 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,

[0743] wherein the C-terminal amino acid of VH forms a peptide bond with the N-terminal amino acid of SEQ ID NO: 182. In some embodiments, the present disclosure contemplates an anti-VISTA mAb comprising:

[0744] A heavy chain consisting of (i) VH of (a) to (ooo) listed above, (ii) the amino acid sequence of SEQ ID NO: 182, and (iii) a Lys residue, wherein the C-terminal amino acid of 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 linked to the N-terminus of Lys; and

[0745] A light chain consisting of the light chain amino acid sequence of (a) to (ooo) listed above;

[0746] wherein the VH and light chain amino acid sequences are selected from the same antibody class from (a) to (ooo) listed above.

[0747] Certain embodiments of the present disclosure include an anti-VISTA Ab comprising:

[0748] (a) a heavy chain comprising (i) the amino acid sequence of 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);

[0749] (b) a heavy chain comprising (i) the amino acid sequence of 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;

[0750] (c) a heavy chain comprising (i) the amino acid sequence of 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;

[0751] (d) a heavy chain comprising (i) the amino acid sequence of 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;

[0752] (e) a heavy chain comprising (i) the amino acid sequence of 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;

[0753] (f) a heavy chain comprising (i) the amino acid sequence of 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;

[0754] (g) a heavy chain comprising (i) the amino acid sequence of 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;

[0755] (h) a heavy chain comprising (i) the amino acid sequence of 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;

[0756] (i) a heavy chain comprising (i) the amino acid sequence of 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;

[0757] (j) a heavy chain comprising (i) the amino acid sequence of 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;

[0758] (k) a heavy chain comprising (i) the amino acid sequence of 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;

[0759] (1) a heavy chain comprising (i) the amino acid sequence of 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;

[0760] (m) a heavy chain comprising (i) the amino acid sequence of 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;

[0761] (n) a heavy chain comprising (i) the amino acid sequence of 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;

[0762] (o) a heavy chain comprising (i) the amino acid sequence of 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;

[0763] (p) a heavy chain comprising (i) the amino acid sequence of 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;

[0764] (q) a heavy chain comprising (i) the amino acid sequence of 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;

[0765] (r) a heavy chain comprising (i) the amino acid sequence of 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;

[0766] (s) a heavy chain comprising (i) the amino acid sequence of 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;

[0767] (t) a heavy chain comprising (i) the amino acid sequence of 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;

[0768] (u) a heavy chain comprising (i) the amino acid sequence of 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;

[0769] (v) a heavy chain comprising (i) the amino acid sequence of 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;

[0770] (w) a heavy chain comprising (i) the amino acid sequence of 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;

[0771] (x) a heavy chain comprising (i) the amino acid sequence of 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;

[0772] (y) a heavy chain comprising (i) the amino acid sequence of 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;

[0773] (z) a heavy chain comprising (i) the amino acid sequence of 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;

[0774] (aa) a heavy chain comprising (i) the amino acid sequence of 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;

[0775] (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: 183 and a light chain comprising the light chain amino acid sequence of P1-068746;

[0776] (cc) a heavy chain comprising (i) the amino acid sequence of 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;

[0777] (dd) a heavy chain comprising (i) the amino acid sequence of 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;

[0778] (ee) a heavy chain comprising (i) the amino acid sequence of 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;

[0779] (ff) a heavy chain comprising (i) the amino acid sequence of 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;

[0780] (gg) a heavy chain comprising (i) the amino acid sequence of 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;

[0781] (hh) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_H100G;

[0782] (ii) a heavy chain comprising the amino acid sequence of (i) 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;

[0783] (jj) a heavy chain comprising the amino acid sequence of (i) 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;

[0784] (kk) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_E30D;

[0785] (ll) a heavy chain comprising the amino acid sequence of (i) 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;

[0786] (mm) a heavy chain comprising (i) the amino acid sequence of 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;

[0787] (nn) a heavy chain comprising the amino acid sequence of (i) 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;

[0788] (oo) a heavy chain comprising the amino acid sequence of (i) 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;

[0789] (pp) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068761_E100fF;

[0790] (qq) a heavy chain comprising the amino acid sequence of (i) 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;

[0791] (rr) a heavy chain comprising the amino acid sequence of (i) 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;

[0792] (ss) a heavy chain comprising the amino acid sequence of (i) 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;

[0793] (tt) a heavy chain comprising the amino acid sequence of (i) 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;

[0794] (uu) a heavy chain comprising the amino acid sequence of (i) 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;

[0795] (vv) a heavy chain comprising the amino acid sequence of (i) 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;

[0796] (ww) a heavy chain comprising the amino acid sequence of (i) 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;

[0797] (xx) a heavy chain comprising the amino acid sequence of (i) 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;

[0798] (yy) a heavy chain comprising the amino acid sequence of (i) 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;

[0799] (zz) a heavy chain comprising the amino acid sequence of (i) 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;

[0800] (aaa) a heavy chain comprising the amino acid sequence of (i) 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;

[0801] (bbb) a heavy chain comprising (i) 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;

[0802] (ccc) a heavy chain comprising the amino acid sequence of (i) 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;

[0803] (ddd) a heavy chain comprising the amino acid sequence of (i) 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;

[0804] (eee) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_D102V;

[0805] (fff) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E55A;

[0806] (ggg) a heavy chain comprising the amino acid sequence of (i) 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;

[0807] (hhh) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E30D_D102V;

[0808] (iii) a heavy chain comprising the amino acid sequence of (i) 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;

[0809] (jjj) a heavy chain comprising (i) 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 comprising the light chain amino acid sequence of P1-068767_E30D_E55A;

[0810] (kkk) a heavy chain comprising the amino acid sequence of (i) 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;

[0811] (111) a heavy chain comprising the amino acid sequence of (i) 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;

[0812] (mmm) a heavy chain comprising the amino acid sequence of (i) 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;

[0813] (nnn) a heavy chain comprising the amino acid sequence of (i) 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

[0814] (ooo) a heavy chain comprising the amino acid sequence of the VH of (i) 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. Certain embodiments of the present disclosure include an anti-VISTA Ab comprising:

[0815] (a) a heavy chain consisting of (i) the VH amino acid sequence 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);

[0816] (b) a heavy chain consisting of (i) the amino acid sequence of 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;

[0817] (c) a heavy chain consisting of (i) the amino acid sequence of 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;

[0818] (d) a heavy chain consisting of (i) the amino acid sequence of 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;

[0819] (e) a heavy chain consisting of (i) the amino acid sequence of 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;

[0820] (f) a heavy chain consisting of (i) the amino acid sequence of 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;

[0821] (g) a heavy chain consisting of (i) the amino acid sequence of 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;

[0822] (h) a heavy chain consisting of (i) the amino acid sequence of 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;

[0823] (i) a heavy chain consisting of (i) the amino acid sequence of 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;

[0824] (j) a heavy chain consisting of (i) the amino acid sequence of 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;

[0825] (k) a heavy chain consisting of (i) the amino acid sequence of 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;

[0826] (l) a heavy chain consisting of (i) the amino acid sequence of 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;

[0827] (m) a heavy chain consisting of (i) the amino acid sequence of 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;

[0828] (n) a heavy chain consisting of (i) the amino acid sequence of 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;

[0829] (o) a heavy chain consisting of (i) the amino acid sequence of 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;

[0830] (p) a heavy chain consisting of (i) the amino acid sequence of 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;

[0831] (q) a heavy chain consisting of (i) the amino acid sequence of 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;

[0832] (r) a heavy chain consisting of (i) the amino acid sequence of 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;

[0833] (s) a heavy chain consisting of (i) the amino acid sequence of 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;

[0834] (t) a heavy chain consisting of (i) the amino acid sequence of 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;

[0835] (u) a heavy chain consisting of (i) the amino acid sequence of 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;

[0836] (v) a heavy chain consisting of (i) the amino acid sequence of 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;

[0837] (w) a heavy chain consisting of (i) the amino acid sequence of 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;

[0838] (x) a heavy chain consisting of (i) the amino acid sequence of 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;

[0839] (y) a heavy chain consisting of (i) the amino acid sequence of 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;

[0840] (z) a heavy chain consisting of (i) the amino acid sequence of 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;

[0841] (aa) a heavy chain consisting of (i) the amino acid sequence of 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;

[0842] (bb) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068746 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain consisting of the light chain amino acid sequence of P1-068746;

[0843] (cc) a heavy chain consisting of (i) the amino acid sequence of 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;

[0844] (dd) a heavy chain consisting of (i) the amino acid sequence of 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;

[0845] (ee) a heavy chain consisting of (i) the amino acid sequence of 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;

[0846] (ff) a heavy chain consisting of (i) the amino acid sequence of 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;

[0847] (gg) a heavy chain consisting of (i) the amino acid sequence of 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;

[0848] (hh) a heavy chain consisting of (i) 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;

[0849] (ii) a heavy chain consisting of the amino acid sequence of (i) 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;

[0850] (jj) a heavy chain consisting of (i) 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;

[0851] (kk) a heavy chain consisting of (i) 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;

[0852] (ll) a heavy chain consisting of (i) the amino acid sequence of 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;

[0853] (mm) a heavy chain consisting of (i) the amino acid sequence of 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;

[0854] (nn) a heavy chain consisting of (i) the amino acid sequence of 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;

[0855] (oo) a heavy chain consisting of the amino acid sequence of (i) 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;

[0856] (pp) a heavy chain consisting of (i) 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;

[0857] (qq) a heavy chain consisting of (i) 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;

[0858] (rr) a heavy chain consisting of (i) 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;

[0859] (ss) a heavy chain consisting of (i) 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;

[0860] (tt) a heavy chain consisting of (i) 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;

[0861] (uu) a heavy chain consisting of (i) 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;

[0862] (vv) a heavy chain consisting of the amino acid sequence of (i) 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;

[0863] (ww) a heavy chain consisting of (i) the amino acid sequence of 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;

[0864] (xx) a heavy chain consisting of the amino acid sequence of (i) the 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;

[0865] (yy) a heavy chain consisting of (i) 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;

[0866] (zz) a heavy chain consisting of the amino acid sequence of (i) the 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;

[0867] (aaa) a heavy chain consisting of (i) 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;

[0868] (bbb) a heavy chain consisting of (i) the amino acid sequence of 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;

[0869] (ccc) a heavy chain consisting of (i) the amino acid sequence of 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;

[0870] (ddd) a heavy chain consisting of (i) 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;

[0871] (eee) a heavy chain consisting of (i) 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;

[0872] (fff) a heavy chain consisting of (i) 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;

[0873] (ggg) a heavy chain consisting of (i) the amino acid sequence of 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;

[0874] (hhh) a heavy chain consisting of (i) 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;

[0875] (iii) a heavy chain consisting of (i) the amino acid sequence of 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;

[0876] (jjj) a heavy chain consisting of (i) 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;

[0877] (kkk) a heavy chain consisting of (i) 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;

[0878] (111) a heavy chain consisting of (i) the amino acid sequence of 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;

[0879] (mmm) a heavy chain consisting of (i) 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;

[0880] (nnn) a heavy chain consisting of (i) the amino acid sequence of 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

[0881] (ooo) a heavy chain consisting of (i) 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,

[0882] wherein the C-terminal amino acid of VH forms a peptide bond with the N-terminal amino acid of SEQ ID NO: 183. In some embodiments, the present disclosure contemplates an anti-VISTA mAb comprising:

[0883] A heavy chain consisting of (i) VH of (a) to (ooo) listed above, (ii) the amino acid sequence of SEQ ID NO: 183, and (iii) a Lys residue, wherein the C-terminal amino acid of 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 linked to the N-terminus of Lys; and

[0884] A light chain consisting of the light chain amino acid sequence of (a) to (ooo) listed above;

[0885] wherein the VH and light chain amino acid sequences are selected from the same antibody class from (a) to (ooo) listed above.

[0886] Other embodiments of the present disclosure include anti-VISTA Abs comprising:

[0887] (a) a heavy chain comprising (i) the amino acid sequence of 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);

[0888] (b) a heavy chain comprising (i) the amino acid sequence of 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;

[0889] (c) a heavy chain comprising (i) the amino acid sequence of 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;

[0890] (d) a heavy chain comprising (i) the amino acid sequence of 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;

[0891] (e) a heavy chain comprising (i) the amino acid sequence of 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;

[0892] (f) a heavy chain comprising (i) the amino acid sequence of 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;

[0893] (g) a heavy chain comprising (i) the amino acid sequence of 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;

[0894] (h) a heavy chain comprising (i) the amino acid sequence of 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;

[0895] (i) a heavy chain comprising (i) the amino acid sequence of 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;

[0896] (j) a heavy chain comprising (i) the amino acid sequence of 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;

[0897] (k) a heavy chain comprising (i) the amino acid sequence of 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;

[0898] (1) a heavy chain comprising (i) the amino acid sequence of 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;

[0899] (m) a heavy chain comprising (i) the amino acid sequence of 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;

[0900] (n) a heavy chain comprising (i) the amino acid sequence of 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;

[0901] (o) a heavy chain comprising (i) the amino acid sequence of 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;

[0902] (p) a heavy chain comprising (i) the amino acid sequence of 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;

[0903] (q) a heavy chain comprising (i) the amino acid sequence of 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;

[0904] (r) a heavy chain comprising (i) the amino acid sequence of 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;

[0905] (s) a heavy chain comprising (i) the amino acid sequence of 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;

[0906] (t) a heavy chain comprising (i) the amino acid sequence of 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;

[0907] (u) a heavy chain comprising (i) the amino acid sequence of 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;

[0908] (v) a heavy chain comprising (i) the amino acid sequence of 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;

[0909] (w) a heavy chain comprising (i) the amino acid sequence of 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;

[0910] (x) a heavy chain comprising (i) the amino acid sequence of 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;

[0911] (y) a heavy chain comprising (i) the amino acid sequence of 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;

[0912] (z) a heavy chain comprising (i) the amino acid sequence of 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;

[0913] (aa) a heavy chain comprising (i) the amino acid sequence of 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;

[0914] (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;

[0915] (cc) a heavy chain comprising (i) the amino acid sequence of 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;

[0916] (dd) a heavy chain comprising (i) the amino acid sequence of 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;

[0917] (ee) a heavy chain comprising (i) the amino acid sequence of 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;

[0918] (ff) a heavy chain comprising (i) the amino acid sequence of 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;

[0919] (gg) a heavy chain comprising (i) the amino acid sequence of 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;

[0920] (hh) a heavy chain comprising (i) the amino acid sequence of 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;

[0921] (ii) a heavy chain comprising the amino acid sequence of (i) 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;

[0922] (jj) a heavy chain comprising the amino acid sequence of (i) 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;

[0923] (kk) a heavy chain comprising (i) the amino acid sequence of 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;

[0924] (ll) a heavy chain comprising the amino acid sequence of (i) 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;

[0925] (mm) a heavy chain comprising (i) the amino acid sequence of 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;

[0926] (nn) a heavy chain comprising the amino acid sequence of (i) 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;

[0927] (oo) a heavy chain comprising the amino acid sequence of (i) 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;

[0928] (pp) a heavy chain comprising (i) the amino acid sequence of 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;

[0929] (qq) a heavy chain comprising the amino acid sequence of (i) 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;

[0930] (rr) a heavy chain comprising the amino acid sequence of (i) 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;

[0931] (ss) a heavy chain comprising the amino acid sequence of (i) 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;

[0932] (tt) a heavy chain comprising the amino acid sequence of (i) 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;

[0933] (uu) a heavy chain comprising the amino acid sequence of (i) 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;

[0934] (vv) a heavy chain comprising the amino acid sequence of (i) 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;

[0935] (ww) a heavy chain comprising the amino acid sequence of (i) 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;

[0936] (xx) a heavy chain comprising the amino acid sequence of (i) 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;

[0937] (yy) a heavy chain comprising the amino acid sequence of (i) 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;

[0938] (zz) a heavy chain comprising the amino acid sequence of (i) 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;

[0939] (aaa) a heavy chain comprising the amino acid sequence of (i) 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;

[0940] (bbb) a heavy chain comprising (i) 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;

[0941] (ccc) a heavy chain comprising the amino acid sequence of (i) 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;

[0942] (ddd) a heavy chain comprising the amino acid sequence of (i) 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;

[0943] (eee) a heavy chain comprising (i) the amino acid sequence of 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;

[0944] (fff) a heavy chain comprising (i) the amino acid sequence of 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;

[0945] (ggg) a heavy chain comprising the amino acid sequence of (i) the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 184, and a light chain comprisin...

Claims

1. An antibody that specifically binds to hVISTA, a T cell activation inhibitor containing human V domain Ig, wherein the antibody comprises: A light chain variable region, VL, and a heavy chain variable region, VH, wherein the light chain variable region VL comprises a VL CDR1, CDR2 and CDR3, which consist of positions 24-35, 51-57 and 90-98 of SEQ ID NO:68, respectively, and the heavy chain variable region VH comprises a VH CDR1, CDR2 and CDR3, which consist of positions 26-35, 50-66 and 99-112 of SEQ ID NO:55, respectively. 2 . The antibody of claim 1 , wherein the antibody comprises a VH comprising the following amino acid sequence: SEQ ID NO:

55.

3. The antibody of claim 1, wherein the antibody comprises a VL comprising the following amino acid sequence: SEQ ID NO:

68. 4 . The antibody of claim 1 , wherein the antibody comprises a VH comprising the following amino acid sequence: SEQ ID NO: 55; and wherein the antibody comprises a VL comprising the following amino acid sequence: SEQ ID NO:

68.

5. The antibody according to any one of claims 1 to 4, wherein the antibody is expressed at 10 -5 M or larger K D Binding to hVISTA, wherein neutral conditions are conditions having a pH of 7.0, and wherein physiological conditions are conditions having a pH of 7.

4.

6. The antibody according to any one of claims 1 to 4, wherein the antibody is 10 -7 M or smaller K D Binding to hVISTA, wherein the acidic condition is a condition having a pH of 6.0 to 6.

5.

7. The antibody according to any one of claims 1 to 4, wherein the antibody is 10 -8 M or smaller K D Binding to hVISTA, wherein the acidic condition is a condition having a pH of 6.0 to 6.

5.

8. The antibody according to any one of claims 1 to 4, wherein the antibody is 10 -9 M or smaller K D Binding to hVISTA, wherein the acidic condition is a condition having a pH of 6.0 to 6.

5.

9. The antibody according to any one of claims 1-4, wherein the antibody has one or more of the following properties: a. Under acidic conditions, the K D At least 10 times lower K D binding to hVISTA, wherein acidic conditions are conditions having a pH of 6.0 to 6.5, wherein neutral conditions are conditions having a pH of 7.0, and wherein physiological conditions are conditions having a pH of 7.4; b. Under acidic conditions, the k is lower than that under neutral or physiological conditions. off At least 5 times lower k off binding to hVISTA, wherein acidic conditions are conditions having a pH of 6.0 to 6.5, wherein neutral conditions are conditions having a pH of 7.0, and wherein physiological conditions are conditions having a pH of 7.4; c. inhibiting the binding of hVISTA to human T cells under conditions having a pH below pH 7.0; d. inhibiting the binding of hVISTA to huPSGL-1 under conditions having a pH below pH 7.0; e. Inhibit the binding of hVISTA to heparan sulfate proteoglycan; f. inhibiting the binding of hVISTA to heparan sulfate proteoglycans under conditions having a pH below pH 7.0; g. stimulating T cell activation under conditions having a pH below pH 7.0; and h. Reduce VISTA-mediated cell-cell adhesion.

10. The antibody according to any one of claims 1-4, wherein the antibody binds at the extracellular domain (ECD) of hVISTA under a pH condition of 6.0 to 6.

5.

11. The antibody according to any one of claims 1 to 4, which is an IgG antibody. The antibody according to claim 11 , which is an IgG1, IgG2 or IgG4 antibody.

13. The antibody according to claim 12, which is an IgG4 antibody having an S228P substitution.

14. The antibody of any one of claims 1-4, wherein the antibody is an effector-free antibody.

15. The antibody of claim 14, wherein the antibody comprises a heavy chain constant region comprising 1-5 mutations that reduce effector function of the antibody.

16. The antibody of any one of claims 1-4, wherein the constant region of the antibody is IgG1.3, IgG1.1, or IgG1 with a P238K substitution.

17. The antibody of any one of claims 1-4, wherein the antibody has effector function.

18. The antibody of claim 17, wherein the antibody is defucosylated.

19. The antibody of claim 17, wherein the antibody comprises a heavy chain constant region comprising 1-5 mutations that enhance effector function of the antibody.

20. The antibody of claim 18, wherein the antibody comprises a heavy chain constant region comprising 1-5 mutations that enhance effector function of the antibody.

21. The antibody of any one of claims 1-4, which is a full-length antibody.

22. The antibody of any one of claims 1-4, which is an antigen binding fragment.

23. The antibody according to any one of claims 1 to 4, which is a multimeric antibody.

24. The antibody of any one of claims 1-4, which is linked to another molecule.

25. The antibody of claim 24, wherein the other molecule is a label or a peptide.

26. The antibody of any one of claims 1-4, which is an antibody drug conjugate.

27. A nucleic acid encoding the antibody according to any one of claims 1-25.

28. A composition comprising a nucleic acid encoding the heavy chain of the antibody according to any one of claims 1-25 and a nucleic acid encoding the light chain of the antibody.

29. A cell comprising the nucleic acid of claim 27 or the composition of claim 28.

30. A method of producing an antibody, comprising culturing the cell according to claim 29 under conditions where the antibody is expressed.

31. A composition comprising the antibody of any one of claims 1-26, the nucleic acid of claim 27, the composition of claim 28 or the cell of claim 29 and a pharmaceutically acceptable carrier.

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