Antibodies that bind to VISTA at acidic pH

Abstract

This application relates to antibodies that specifically bind to V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA) at acidic pH and their use in cancer treatment. In some embodiments, the antibodies specifically bind to human VISTA at acidic pH but do not significantly bind to human VISTA at neutral or physiological pH.

Description

Technical Field

[0001] The present application relates to an antibody that specifically binds to the V-domain immunoglobulin-containing suppressor of T cell activation (VISTA) at acidic pH and its use in cancer treatment.

Background Art

[0002] The V-domain Ig-containing suppressor of T cell activation, or VISTA, is a co-inhibitory member of the B7 family of immunoreceptors expressed by myeloid monocytes and other leukocytes. However, the mechanism by which VISTA suppresses the immune response is not fully understood.

Summary of the Invention

Problems to be Solved by the Invention

[0003] The inventors have found that, unlike other known immunoreceptors, VISTA binds to its counter-receptor, functions selectively at acidic pH, and has little activity at physiological pH (e.g., 7.3 - 7.4). Thus, VISTA can suppress the immune response in acidic microenvironments such as tumor niches or sites of inflammation without disturbing cell circulation in the blood or while in non-inflammatory, non-acidic tissues. Furthermore, the inventors have found that anti-VISTA antibodies can be engineered to selectively bind to VISTA at acidic pH and bind little or not at all at physiological pH, mimicking the acidic pH selectivity of VISTA itself. These acidic pH-selective antibodies can provide desirable properties for treating diseases such as cancer compared to antibodies that bind VISTA at physiological pH.

Means for Solving the Problems

[0004] The present disclosure relates to antibodies that specifically bind to the extracellular domain (ECD) of VISTA, such as human VISTA (“hVISTA” or “huVISTA”), at acidic pH (e.g., under acidic conditions). The present disclosure also relates to antibodies that specifically bind to the extracellular domain (ECD) of VISTA, such as hVISTA, at acidic pH but bind little or not at all at neutral or physiological pH. The inventors noted herein that the hVISTA-ECD amino acid sequence contains several conserved as well as non-conserved histidine residues and that the frequency of histidine residues in the ECD of VISTA is exceptionally high compared to other B7 family members and other immunoglobulin superfamily members (see FIGS. 1A and 1B). In solution, the amino acid histidine has a pK a of about 6.5, which means that below pH 6.5, histidine residues in proteins are often protonated and thus have a positive charge, while at pH higher than 6.5, they become increasingly deprotonated and have a neutral charge. Tumor microenvironments and inflamed tissues are often acidic, and thus the VISTA protein found in these microenvironments can be at least partially protonated at its histidine residues. The inventors hypothesized that, as discussed herein, histidine protonation can affect the conformation, surface structure, and / or charge density of VISTA, and can then create pH-specific or pH-selective epitopes for both receptor-ligand interactions and antibody binding. Targeting VISTA with antibodies that bind at acidic pH but not at neutral or physiological pH can avoid target-mediated pharmacokinetics via bone marrow monocytic cells resident in the circulatory and lymphoid organs, and improve antibody PK, receptor occupancy, and activity in the tumor microenvironment. Acidic pH-selective antibodies can also improve the specificity of VISTA antibodies for in-tumor target cells compared to circulating target cells in the case of therapeutic modalities such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and delivery of payloads (antibody-drug conjugates).

[0005] Color versions of some of the figures in this specification were provided to the United States Patent and Trademark Office in connection with the filing of a provisional application for priority in the United States. Once this application is published, the provisional application will be publicly available, and the United States Patent and Trademark Office is presumed to provide the color drawings upon payment of the claims and the required fees.

Brief Description of the Drawings

[0006]

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DETAILED DESCRIPTION OF THE INVENTION

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

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

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

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

[0011] The term "antibody" or "Ab" is used herein in a broad sense and includes, but is not limited to, various antibody structures including 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, this term refers to a molecule that includes at least complementarity-determining regions (CDRs) 1, 2, and 3 of the heavy chain and at least CDRs 1, 2, and 3 of the light chain, and the molecule is capable of binding to an antigen. The term "antibody" includes, but is not limited to, fragments that are capable of binding to an antigen, such as "antigen-binding fragments" or "antibody fragments", e.g., Fv, single-chain Fv (scFv), Fab, Fab' and (Fab')2. The term "antibody" also includes, but is not limited to, chimeric antibodies, humanized antibodies, human antibodies and antibodies of various species such as mouse, cynomolgus monkey, etc.

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

[0013] The term "heavy chain variable region" or "VH" refers to the region of the heavy chain that includes heavy chain complementarity determining region (CDR)1, framework region (FR)2, CDR2, FR3, and CDR3. In some embodiments, the heavy chain variable region also includes at least a portion of FR1 and / or at least a portion of FR4. As detailed below, in some embodiments, the heavy chain CDR1 includes residues 26-35 of the VH sequence number herein, the heavy chain CDR2 includes residues 50-66 of the VH sequence number herein, and the heavy chain CDR3 includes residues 99-110 of the VH sequence number herein. In other embodiments, when specified, the heavy chain CDR1 corresponds to Kabat residues 31-35, the heavy chain CDR2 corresponds to Kabat residues 50-65, and the heavy chain CDR3 corresponds to Kabat residues 95-102. See, e.g., Kabat Sequences of Proteins of Immunological Interest (1987 and 1991, NIH, Bethesda, Md.). In some embodiments, the heavy chain CDRs are as specified herein, e.g., in the following sequence listing, or in Table 2.

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

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

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

[0017] The term "humanized antibody" refers to an antibody in which at least one amino acid in the framework region of the non-human variable region is replaced with the corresponding amino acid derived 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.

[0018] As used herein, the term "human antibody" refers to an antibody produced in a human, an antibody produced in a non-human animal comprising a human immunoglobulin gene, e.g., XenoMouse® and antibodies selected using in vitro methods, e.g., phage display in which the antibody repertoire is based on human immunoglobulin sequences.

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

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

[0021] The "K D " or "dissociation constant" of the binding of an antibody protein, e.g., to a VISTA-ECD protein, is a measure of the affinity or specific binding of the antibody protein, e.g., to a VISTA-ECD protein. A low K D is a high KD shows improved binding or affinity that exceeds K. D is the "off-rate" or k of an antibody and a polypeptide off or k d and the "on-rate" or k on or k a and is composed of the ratio between them. The off-rate and on-rate are the rates at which two binding partners associate and dissociate in that system. Thus, a slower off-rate while the on-rate remains approximately constant leads to a higher overall affinity and, thus, a lower K. D As used herein, a particular value "less than" k off means that k off or the "off-rate" is as specified or slower than the specified rate.

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

[0023] In some embodiments, the antibody specifically binds to the VISTA-ECD protein at a specific pH or pH range. As used herein, "acidic" pH generally refers to a pH less than 7.0, "basic" pH generally refers to a pH greater than 7.0, and "neutral" pH generally refers to a pH of about 7.0. As used herein, "physiological pH" refers to a pH of, for example, 7.35 - 7.45, or 7.3 - 7.4, for example, about 7.4, under normal (i.e., non-cancerous) physiological conditions. Phrases such as "binding under acidic conditions" or "binding under physiological conditions" as used herein in the context of the binding of two molecules such as VISTA and a VISTA binding partner or VISTA and a T cell refer to binding at acidic pH and binding at physiological pH, respectively.

[0024] When referring to an antibody that "blocks the binding of" or "inhibits the binding of" a ligand (or receptor) or a competing antibody, either alone or with a receptor (or ligand) on a cell, binding is blocked when there is an overall decrease that is statistically significant compared to a control, for example, an overall decrease of 50% or more, for example, an overall decrease of 75%, 80%, 85%, 90%, 95% or more. An "anti-VISTA blocking antibody," for example, can block the binding of VISTA to PSGL-1 or another VISTA ligand or receptor or heparan sulfate proteoglycan, at least under some conditions, for example, at acidic pH.

[0025] As used herein, a "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 syngeneic mouse tumor assay systems. In some cases, the tumor model allows for tracking of tumor size or growth upon treatment with the antibody and / or tracking of the presence of immune cells in the tumor, for example, a particular type of T cell or NK cell, and can examine whether the antibody has elicited or enhanced an immune response.

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

[0027] "Percent amino acid sequence identity (%)" and "homology" with respect to a peptide, polypeptide or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in a particular peptide or polypeptide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity without considering any conservative substitutions as part of the sequence identity. Alignments for the purpose of determining percent amino acid sequence identity can be achieved by various methods within the skill in the art, e.g., using publicly available computer software such as BLAST, BLAST-2, ALIGN or MEGALIGNTM (DNASTAR) software. One of ordinary skill in the art can determine appropriate parameters for measuring the alignment, including any algorithm required to achieve the maximum alignment over the entire length of the sequences being compared.

[0028] The terms "induce" or "enhance" refer to the initiation or increase of any event (e.g., protein ligand binding) or any biological activity (e.g., immune response) or phenotypic characteristic or the initiation or increase of the incidence, degree or likelihood of that activity or characteristic. "Induce" or "enhance" means to initiate or increase an activity, function and / or amount as compared to a reference. It is not necessary that the inducing or enhancing be complete. For example, in certain embodiments, "enhance" means the ability to cause an overall increase of 20% or more. In another embodiment, "enhance" means the ability to cause an overall increase of 50% or more. In yet another embodiment, "enhance" means the ability to cause an overall increase of 75%, 85%, 90%, 95% or more.

[0029] The terms "inhibit" or "inhibiting" more generally refer to a decrease or interruption of any event (e.g., protein-ligand binding), or a decrease or interruption of any phenotypic characteristic, or a decrease or interruption in the incidence, degree, or likelihood of that characteristic. "Reducing" or "inhibiting" means decreasing, lowering, or stopping the activity, function, and / or amount as compared to a reference. It is not necessary for the inhibition or reduction to be complete. For example, in certain embodiments, "reducing" or "inhibiting" means the ability to cause an overall decrease of 20% or more. In another embodiment, "reducing" or "inhibiting" means the ability to cause an overall decrease of 50% or more. In yet another embodiment, "reducing" or "inhibiting" means the ability to cause an overall decrease of 75%, 85%, 90%, 95% or more.

[0030] As used herein, "treatment" is directed to any administration or application of a therapeutic agent for a disease in a human, and includes inhibiting the progression of the disease or a disease or one or more disease symptoms, inhibiting or slowing the progression of the disease or one or more of its symptoms, partially or completely alleviating the disease or one or more of its symptoms, or preventing the recurrence of one or more symptoms of the disease.

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

[0032] The term "effective amount" or "therapeutically effective amount" refers to the amount of a drug that is effective in treating a disease or disorder in a subject as compared to a control to partially or completely alleviate one or more symptoms. In some embodiments, an effective amount refers to an amount effective with respect to the dosage and time required to achieve the desired therapeutic or prophylactic result.

[0033] As used herein, the term "cancer" refers to a group of cells that exhibit abnormally high levels of proliferation and growth. Cancer can be benign (also referred to as a benign tumor), pre-malignant or malignant. Cancer cells can be solid cancer cells or leukemia cancer cells. As used herein, the term "tumor growth" refers to the proliferation or growth by cells (singular or plural) that include cancer leading to a corresponding increase in the size or extent of the cancer.

[0034] Examples of cancers applicable to the methods of treatment herein include, but are not limited to, carcinomas, lymphomas, blastomas, sarcomas and leukemias. More particularly, 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 non-small cell lung cancer), lung adenocarcinoma, lung squamous cell carcinoma, peritoneal cancer, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, renal cell carcinoma, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, liver carcinoma, brain cancer, endometrial cancer, testicular cancer, cholangiocarcinoma, gallbladder carcinoma, stomach cancer, melanoma and various types of head and neck cancers (including squamous cell carcinoma of the head and neck).

[0035] Administration "in combination with" one or more additional therapeutic agents includes simultaneous (co-administration) and sequential (sequential) administration in any order.

[0036] "Pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid or liquid bulking agent, diluent, encapsulating material, formulation aid or conventional carrier in the art for use with a therapeutic agent that together with the "pharmaceutical composition" for administration to a subject. A pharmaceutically acceptable carrier is non-toxic to the recipient at the dosages and concentrations employed and is compatible with the other ingredients of the formulation. A pharmaceutically acceptable carrier is suitable for the formulation employed. For example, if the therapeutic agent is intended for oral administration, the carrier can be a gel capsule. If the therapeutic agent is intended for subcutaneous administration, the carrier is preferably not irritating to the skin and does not cause an injection site reaction.

[0037] "Chemotherapeutic agents" are compounds useful in the treatment of cancer. Examples of chemotherapeutic agents that can be administered in the methods described herein include, but are not limited to, alkylating agents such as thiotepa and cytoxan (registered trademark) cyclophosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carbocone, meturedopa and uredopa; ethyleneimine and methylamelamine including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylolmelamine; acetogenins (especially, bullatacin and bullatacinone); camptothecin (including the synthetic analog topotecan); bryostatin; calistatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogs); cryptophycin (especially, cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogs, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chloronaphazine, colophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembicin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine and ranimustine; antibiotics such as enediyne antibiotics (e.g., calicheamicin, especially, calicheamicin gamma1I and calicheamicin omegaI1 (see, e.g., Agnew, Chem Intl. Ed. Engl., 33: 183-186 (1994)); dynemicin A including dynemicin; bisphosphonates such as clodronate; esperamicin;and neocarzinostatin chromophore and related pigment protein enediyne antibiotic chromophores), actinomycins, aclacinomycins, authramycin, azaserine, bleomycin, cactinomycin, carabicin, calminomycin, cardinophilin, chromomycinis, daunorubicin, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycin, for example, mitomycin C, mycophenolic acid, nogalamycin, olivomycin, peplomycin, potfiromycin, puromycin, quelamycin, rhodomycin, streptozocin, streptozocin, tubercidin, ubenimex, dinostatin, zorubicin; antimetabolites, for example, methotrexate and 5-fluorouracil (5-FU); folic acid analogs, for example, denopterin, methotrexate, pteropterin, trimethoprim; purine analogs, for example, fludarabine, 6-mercaptopurine, thiampurine, thioguanine; pyrimidine analogs, for example, ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, didoxyruridine, doxifluridine, enocitabine, floxuridine; androgens, for example, calusterone, drostanolone propionate, epitestosterone, mepitiostane, testolactone; anti-adrenals, for example, aminoglutethimide, mitotane, trilostane; folic acid replenisher, for example, folinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; dexamethasone; diaziquone; elfornithine; elliptinium acetate; epothilone;Etoposide; Gallium Nitrate; Hydroxyurea; Lentinan; Lonidainine; Maytansinoids, such as Maytansine and Ansamitocin; Mitoguazone; Mitoxantrone; Mopidanmol; Nitraerine; Pentostatin; Phenamet; Pirarubicin; Losoxantrone; Podophyllinic Acid; 2-Ethylhydrazide; Procarbazine; PSK® Polysaccharide Complex (JHS Natural Products, Eugene, OR); Razoxane; Rizoxin; Schizophyllan; Spirogermanium; Tenuazonic Acid; Triaziquone; 2,2’,2’’-Trichlorotriethylamine; Trichothecenes (especially, T-2 Toxin, Verracurin A, Lolitrem A and Anguizine); Urethane; Vinblastine; Dacarbazine; Mannomustine; Mitobronitol; Mitolactol; Pipobroman; Gacytosine; Arabinoside (“Ara-C”); Cyclophosphamide; Thiotepa; Taxoids, such as Taxol® Paclitaxel (Bristol-Myers Squibb Oncology, Princeton, NJ), Abraxane® Cremophor-free, Albumin-engineered Nanoparticle Formulation of Paclitaxel (American Pharmaceutical Partners, Schaumburg, IL) and Taxotere® Docetaxel (Rhone-Poulenc Rorer, Antony, France); Chlorambucil; Gemzar® Gemcitabine; 6-Thioguanine; Mercaptopurine; Methotrexate; Platinum Analogues, such as Cisplatin, Oxaliplatin and Carboplatin; Vinblastine; Platinum; Etoposide (VP-16); Ifosfamide; Mitoxantrone; Vincristine; Navelbine® Vinorelbine; Novantrone; Teniposide; Edatrexate; Daunomycin; Aminopterin; Xeloda; Ibandronate; Irinotecan (Camptosar, CPT-11) (including treatment regimens of irinotecan together with 5-FU and Leucovorin); Topoisomerase Inhibitor RFS2000; Difluoromethylornithine (DMFO);Retinoids, such as retinoic acid; capecitabine; combretastatin; leucovorin (LV); oxaliplatin; inhibitors of PKC-alpha, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva®)) and VEGF-A that reduce cell proliferation, and pharmaceutically acceptable salts, acids or derivatives of any of the foregoing.

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

[0039] "Anti-angiogenic agent" or "angiogenesis inhibitor" refers to a low molecular weight substance, polynucleotide [e.g., including inhibitory RNA (RNAi or siRNA)], polypeptide, isolated protein, recombinant protein, antibody or its conjugate or fusion protein that directly or indirectly inhibits angiogenesis, vasculogenesis or undesirable vascular permeability. It should be understood that anti-angiogenic agents include substances that bind and block the angiogenic activity of angiogenic factors or their receptors. For example, as anti-angiogenic agents that can be administered in the methods herein, antibodies or other antagonists to angiogenic agents, such as antibodies to VEGF-A [e.g., bevacizumab (Avastin®)] or antibodies to VEGF-A receptors (e.g., KDR receptor or Flt-1 receptor), anti-PDGFR inhibitors, such as Gleevec® (imatinib mesylate), small molecules that block VEGF receptor signaling (e.g., PTK787 / ZK2284, SU6668, Sutent® / SU11248 (sunitinib malate), AMG706 or those described, for example, in International Patent Application WO2004 / 113304) are included. Also included as anti-angiogenesis agents are natural angiogenesis inhibitors, such as angiostatin, endostatin, etc. See, for example, Klagsbrun and D’Amore (1991) Annu. Rev. Physiol. 53:217-39; Streit and Detmar (2003) Oncogene 22:3172-3179 (e.g., Table 3 listing anti-angiogenic therapies in malignant melanoma); Ferrara & Alitalo (1999) Nature Medicine 5(12):1359-1364; Tonini et al. (2003) Oncogene 22:6549-6556 (e.g., Table 2 listing known angiogenic factors); and, Sato (2003) Int. J. Clin. Oncol. 8:200-206 (e.g., Table 1 listing anti-angiogenic agents used in clinical trials).

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

[0041] The term "antineoplastic composition" refers to a composition useful for treating cancer that contains at least one active therapeutic agent. Examples of therapeutic agents include, but are not limited to, for example, chemotherapeutic agents, growth inhibitors, cytotoxic agents, substances used in radiotherapy, anti-angiogenic agents, cancer immunotherapeutic agents, apoptosis agents, anti-tubulin agents and other agents for treating cancer, such as anti-HER-2 antibodies, anti-CD20 antibodies, epidermal growth factor receptor (EGFR) antagonists (e.g., tyrosine kinase inhibitors), HER1 / EGFR inhibitors (e.g., erlotinib (Tarceva®)), platelet-derived growth factor inhibitors (e.g., Gleevec® (imatinib mesylate)), COX-2 inhibitors (e.g., celecoxib), interferons, CTLA4 inhibitors (e.g., anti-CTLA antibody ipilimumab (Yervoy®)), PD-1 or (or) PD-L1 inhibitors (e.g., Opdivo®, Keytruda®, Tecentriq®, Bavencio®, Imfinzi®), TIM3 inhibitors (e.g., anti-TIM3 antibody), cytokines, antagonists (e.g., neutralizing antibodies) that bind to one or more of the following target ErbB2, ErbB3, ErbB4, PDGFR-beta, BlyS, APRIL, BCMA, CTLA4, TIM3 or VEGF receptors, TRAIL / Apo2 and other bioactive and organic chemical substances, etc. Combinations thereof are also included in the present disclosure.

[0042] An antibody that specifically binds to VISTA-ECD at acidic pH Since VISTA has a number of histidine residues in its extracellular domain (ECD), the folding and overall structure and the surface available for binding of ligands such as antibodies may differ at acidic pH compared to neutral pH, particularly around pH 6.5 which is the pK of histidine. a The tumor microenvironment is generally acidic, so for binding to VISTA in those microenvironments, the antibody may need to bind specifically to VISTA at an acidic pH where at least some of the surface histidine residues are more likely to be protonated.

[0043] The following sequence listings provide the amino acid sequences of human VISTA (hVISTA) with or without a signal peptide (SEQ ID NO: 1 and SEQ ID NO: 2 (mature hVISTA)), respectively. The signal peptide consists of amino acid residues 1 to 32 of SEQ ID NO: 1. The extracellular domain (ECD) consists of amino acid residues 1 to 162 of SEQ ID NO: 2). The IgV domain consists of amino acid residues 37 to 167 of SEQ ID NO: 1 and amino acid residues 5 to 135 of SEQ ID NO: 2. The stalk region is at amino acid residues 172 to 194 of SEQ ID NO: 1 and amino acid residues 136 to 162 of SEQ ID NO: 2, and the transmembrane domain is at amino acid residues 195 to 216 of SEQ ID NO: 1 and amino acid residues 163 to 184 of SEQ ID NO: 2. Amino acid residue 187 of SEQ ID NO: 1 and 155 of SEQ ID NO: 2 (bold and underlined) may be either D or E, which corresponds to a polymorphism in hVISTA. The residues are shown in bold and underlined. Thus, SEQ ID NO: 1 and SEQ ID NO: 2 encompass both human polymorphisms at those residues. Histidine residues in the ECD of VISTA are shaded in gray.

[0044] An anti-VISTA antibody (Ab) can specifically bind to, for example, the IgV domain of VISTA or a VISTA-ECD or a fragment thereof derived from hVISTA containing 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 an acidic pH. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 7.0. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 6.8. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 6.5. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 6.3. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 6.0. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 5.8. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 5.5. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 5.3. In certain embodiments, the Ab specifically binds to the VISTA-ECD protein at a pH less than 5.0.

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

[0046] VISTA-ECD proteins, such as the IgV domain of VISTA or, for example, regions derived from hVISTA containing amino acids 20-95, 20-70, 35-70, 35-95, 35-127 or 37-125 of SEQ ID NO: 2, or fragments thereof, and, at a pH of 6.5 or less, 10 -6 M or less of K D to bind the Ab are also provided herein. In some embodiments, the Ab binds at 10 -7 M or less of K D to bind. In some embodiments, the Ab binds at 10 -8 M or less of K D to bind. In some embodiments, the Ab binds at 10 -9 M or less of K D to bind. In some embodiments, the Ab binds at 10 -10 M or less of K D to bind. For example, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less and 10 -8 M or less of K D to bind.

[0047] Ab that binds to the VISTA-ECD protein within a pH range of 6.0 - 6.5 and at 10 -6 M or less of K D are also provided herein. In some embodiments, the Ab binds at 10 -7 M or less of K D to bind. In some embodiments, the Ab binds at 10 -8 M or less of K D to bind. In some embodiments, the Ab binds at 10 -9 M or less of K D to bind. In some embodiments, the Ab binds at 10 -10 M or less of K D to bind. For example, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, for example, within a pH range of 6.0 - 6.5, and at 10 -7 M or less of K D to bind. Further, the Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less, for example, within a pH range of 6.0 - 6.5, and at 10-8 K below M D and can bind. Ab can bind to hVISTA-ECD at a pH of 6.5 or lower, for example, within a pH range of 6.0 to 6.5, with a K of 10 -9 M or lower D and can bind.

[0048] VISTA-ECD protein, for example, the IgV domain of VISTA or a region derived from hVISTA containing, for example, amino acids 20 to 95, 20 to 70, 35 to 70, 35 to 95, 35 to 127, or 37 to 125 of SEQ ID NO: 2, or a fragment thereof, and, for example, at a pH of 6.5 or lower, at 25°C, or at 37°C, with a K of 10 -5 s -1 or lower k off and specifically binds an Ab that is also provided herein. In some embodiments, the Ab has a k of 10 at 25°C or at 37°C -4 s -1 or lower off In some embodiments, the Ab has a k of 2×10 at 25°C or at 37°C -4 s -1 or lower off In some embodiments, the Ab has a k of 5×10 at 25°C or at 37°C -4 s -1 or lower off In some embodiments, the Ab has a k of 7×10 at 25°C or at 37°C -4 s -1 or lower off In some embodiments, the Ab has a k of 10 at 25°C or at 37°C -3 s -1 or lower off In some embodiments, the Ab has a k of 2×10 at 25°C or at 37°C -3 s -1 or lower off In some embodiments, the Ab has a k of 5×10 at 25°C or at 37°C -3 s -1 or lower off In some embodiments, the Ab has a k of 7×10 at 25°C or at 37°C -3 s -1 or loweroff has. In some embodiments, Ab is at 25 °C or at 37 °C for 10 -2 s -1 or less of k off has. In some embodiments, at 25 °C or at 37 °C for 10 -1 s -1 or less of k off has. For example, Ab is with the VISTA-ECD protein, at a pH of 6.5 or less, at 25 °C or at 37 °C for 10 -3 s -1 or less of k off and can specifically bind. Ab is with the hVISTA-ECD protein, at a pH of 6.5 or less, at 25 °C or at 37 °C for 10 -3 s -1 or less of k off and can specifically bind. Further, Ab is with the VISTA-ECD protein, at a pH of 6.5 or less, at 25 °C or at 37 °C for 10 -2 s -1 or less of k off and can specifically bind.

[0049] The VISTA-ECD protein, for example, the IgV domain of VISTA or, for example, the region derived from hVISTA containing amino acids 20-95, 20-70, 35-70, 35-95, 35-127 or 37-125 of SEQ ID NO: 2, or a fragment thereof, and, for example, at a pH of 6.5 or less, (i) 10 -6 M or less, 10 -7 M or less, 10 -8 M or less, 10 -9 M or less or 10 -10 M or less of K D and (ii) for example, as measured at 25 °C or at 37 °C, 10 -5 s -‘1 or less, 10 -4 (or 2, 5 or 7 10 -4 ) or less, 10 -3 (or 2, 5 or 7 10 -4 )s -1 or less, 10 -2 s -1 or less or 10 -1 s -1The following k off Abs that bind at the following rate are provided herein. For example, an Ab binds to a VISTA-ECD protein at a pH of 6.5 or less and a K -7 of 10 D M or less, and for example, 10 -3 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. An Ab binds to a VISTA-ECD protein at a pH of 6.5 or less and a K -8 of 10 D M or less, and for example, 10 -3 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. An Ab binds to a VISTA-ECD protein at a pH of 6.5 or less and a K -8 of 10 D M or less, and for example, 10 -2 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. For example, an Ab binds to an hVISTA-ECD protein at a pH of 6.5 or less and a K -7 of 10 D M or less, and for example, 10 -3 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. An Ab binds to an hVISTA-ECD protein at a pH of 6.5 or less and a K -9 of 10 D M or less, and for example, 10 -3 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. An Ab binds to an hVISTA-ECD protein at a pH of 6.5 or less and a K -9 of 10 D M or less, and for example, 10 -2 s -1 at 25°C or as measured at 37°C. The following k off Abs may bind at the following rate. An Ab binds to an hVISTA-ECD protein at a pH of 6.5 or less and a K -8 of 10 Dand, for example, as measured at 25 °C or 37 °C, 10 -4 (or 2, 5 or 7 10 -4 ) s -1 at the following k off speed can bind. Ab is the hVISTA-ECD protein and at a pH of 6.5 or less, 10 -8 M or less of K D and, for example, as measured at 25 °C or 37 °C, 10 -5 (or 2, 5 or 7 10 -5 ) s -1 at the following k off speed can bind. Ab is the hVISTA-ECD protein and at a pH of 6.5 or less, 10 -9 M or less of K D and, for example, as measured at 25 °C or 37 °C, 10 -4 (or 2, 5 or 7 10 -4 ) s -1 at the following k off speed can bind. Ab is the hVISTA-ECD protein and at a pH of 6.5 or less, 10 -9 M or less of K D and, for example, as measured at 25 °C or 37 °C, 10 -5 (or 2, 5 or 7 10 -5 ) s -1 at the following k off speed can bind.

[0050] An Ab that specifically binds to the VISTA-ECD protein, for example, at a pH of 6.5 or less, at 25 °C or 37 °C, 10 4 M -1 s -1 at a high k of or more on is provided herein. In some such embodiments, the Ab is 10 5 M -1 s -1 at a k of or more on can bind. In some such embodiments, the Ab is 10 6 M -1 s -1 at a k of or more on can bind. In some such embodiments, the Ab is 107 M -1 s -1 can be combined with the above k on For example, Ab can be combined with the VISTA-ECD protein at a pH of 6.5 or less, for example, at 25 °C or 37 °C, and 10 6 M -1 s -1 can be combined with the above k on For example, Ab can be combined with the ECD of hVISTA at a pH of 6.5 or less, for example, at 25 °C or 37 °C, and 10 6 M -1 s -1 can be combined with the above k on and can be combined with k above.

[0051] VISTA-ECD protein, for example, at a pH of 6.5 or less, (i) 10 -6 M or less, 10 -7 M or less, 10 -8 M or less, 10 -9 M or less or 10 -10 M or less of K D and (ii) for example, at 25 °C or 37 °C, and 10 4 M -1 s -1 or more, 10 5 M -1 s -1 or more, 10 6 M -1 s -1 or more, 10 7 M -1 s -1 can be combined with the above k on and Ab that binds at a rate of k above is provided herein. For example, Ab can be combined with the VISTA-ECD protein at a pH of 6.5 or less, 10 -7 M or less of K D and for example, at 25 °C or 37 °C, and 10 6 M -1 s -1 can be combined with the above k on at a rate. For example, Ab can be combined with the VISTA-ECD protein at a pH of 6.5 or less, 10 -8 M or less of K Dand, for example, at 25 °C or as measured at 37 °C, 10 6 M -1 s -1 or higher k on rates can bind. For example, Ab can bind to hVISTA-ECD at a pH of 6.5 or lower and at 10 -7 M or lower K D and, for example, at 25 °C or as measured at 37 °C, 10 6 M -1 s -1 or higher high k on rates can bind. For example, Ab can bind to hVISTA-ECD at a pH of 6.5 or lower and at 10 -8 M or lower K D and, for example, at 25 °C or as measured at 37 °C, 10 6 M -1 s -1 or higher k on rates can bind.

[0052] In some embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or lower and at 10 -7 M or lower K D and, for example, at 25 °C or as measured at 37 °C, 10 -5 s -1 or less, 2 10 -5 s -1 or less, 5 10 -5 s -1 or less, 7 10 -5 s -1 or less, 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 less, 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 less, 10 -2 s -1 or less or 10-1 s -1 The following k off can bind. In some embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -9 M or less, and for example, as measured at 25°C or 37°C, 10 D s -5 or less, 10 -1 s -4 or less, 10 -1 s -3 or less, 10 -1 s -2 or less, 10 -1 s or 10 -1 s -1 or less of k off can bind. In some such embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -10 M or less, and for example, as measured at 25°C or 37°C, 10 D s -5 or less, 10 -1 s -4 or less, 10 -1 s -3 or less, 10 -1 s -2 or less, 10 -1 s or 10 -1 s -1 or less of k off can bind.

[0053] In some embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -7 M or less, and for example, as measured at 25°C or 37°C, 10 D M 4 or more, 10 -1 M -1 or more, 10 5 M -1 or more, 10 -1 M 6 or more, 10 -1 M -1 or more, 10 7 M -1 or more, 10 -1 or more of k oncan bind. In some embodiments, Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -8 M or less, D and, for example, as measured at 25 °C or 37 °C, a k of 10 4 M -1 s or more, 10 -1 M 5 s or more, 10 -1 M -1 s or more, 10 6 M -1 s or more, 10 -1 M 7 s or more, 10 -1 M -1 s or more, and a k of 10 on or more. In some embodiments, Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -9 M or less, D and, for example, as measured at 25 °C or 37 °C, a k of 10 4 M -1 s or more, 10 -1 M 5 s or more, 10 -1 M -1 s or more, 10 6 M -1 s or more, 10 -1 M 7 s or more, 10 -1 M -1 s or more, and a k of 10 on or more. In some such embodiments, Ab can bind to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -10 M or less, D and, for example, as measured at 25 °C or 37 °C, a k of 10 4 M -1 s or more, 10 -1 M 5 s or more, 10 -1 M -1 s or more, 10 6 M -1 s or more, 10 -1 M 7 s or more, 10 -1 M -1 s or more, and a k of 10 on or more.

[0054] In some embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -7 M or less D and, for example, as measured at 25 °C or 37 °C, a k of 10 -5 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -4 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -3 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -2 s or less -1 or 10 -1 s or less -1 of k and, for example, as measured at 25 °C or 37 °C, a K of 10 off M or more 4 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 5 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more 6 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 7 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more of k and, for example, as measured at 25 °C or 37 °C, a K of 10 on M or less and a K of 10 -8 M or less D and, for example, as measured at 25 °C or 37 °C, a k of 10 -5 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -4 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -3 s or less -1 and, for example, as measured at 25 °C or 37 °C, a k of 10 -2 s or less -1 or 10 -1 s or less -1 of k and, for example, as measured at 25 °C or 37 °C, a K of 10 off M or more 4 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 5 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more 6 and, for example, as measured at 25 °C or 37 °C, a K of 10 -1 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10 7 M or more -1 and, for example, as measured at 25 °C or 37 °C, a K of 10-1 The above k on can bind. In some embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -9 M or less, and for example, as measured at 25°C or 37°C, 10 D s or less, 10 -5 s or less, 10 -1 s or less, 10 -4 s or less, 10 -1 s or less, 10 -3 s or less, 10 -1 s or less, 10 -2 s or less, 10 -1 s or less or 10 -1 s or less of k, and for example, as measured at 25°C or 37°C, 10 -1 M or more, 10 off M or more, 10 4 M or more, 10 -1 s or more, 10 -1 M or more, 10 5 M or more, 10 -1 s or more, 10 -1 M or more, 10 6 M or more, 10 -1 s or more, 10 -1 M or more, 10 7 M or more, 10 -1 s or more, 10 -1 M or more of k, and for example, as measured at 25°C or 37°C, 10 on can bind. In some such embodiments, Ab binds to the VISTA-ECD protein at a pH of 6.5 or less and a K of 10 -10 M or less, and for example, as measured at 25°C or 37°C, 10 D s or less, 10 -5 s or less, 10 -1 s or less, 10 -4 s or less, 10 -1 s or less, 10 -3 s or less, 10 -1 s or less, 10 -2 s or less, 10 -1 s or less or 10 -1 s or less of k, and for example, as measured at 25°C or 37°C, 10 -1 M or more, 10 off M or more, 10 4 M or more, 10 -1 s or more, 10 -1 M or more, 10 5 M or more, 10 -1 s or more, 10 -1 M or more, 10 6 M or more, 10 -1 s or more, 10 -1Above, 10 7 M -1 s -1 Above k on can be combined with.

[0055] As noted above, in some of the above embodiments, the VISTA-ECD protein is hVISTA-ECD or a part of hVISTA-ECD, such as the IgV domain. In some of the above embodiments, the Ab can specifically bind to an epitope comprising amino acids 20-95 of SEQ ID NO: 2. In some of the above embodiments, the Ab can specifically bind to an epitope comprising amino acids 20-70 of SEQ ID NO: 2. In some of the above embodiments, the Ab can specifically bind to an epitope comprising amino acids 35-95 of SEQ ID NO: 2. In some of the above embodiments, the Ab can specifically bind to an epitope comprising amino acids 35-70 of SEQ ID NO: 2. In some of these embodiments, the epitope is not only one of the above parts of SEQ ID NO: 2 derived from residues 20-95, 20-70, 35-95 or 35-70, but also another part of SEQ ID NO: 2, such as residues 95-105 of SEQ ID NO: 2, and is a three-dimensional epitope. In certain embodiments, the Ab binds to an epitope of hVISTA to which the Ab described in WO2015 / 097536 binds. For example, the Ab can compete or cross-compete with the Ab disclosed in WO2015 / 097536 for binding to hVISTA. In certain embodiments, the Ab binds to a conformational epitope of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising or present in residues 103-111 of SEQ ID NO: 2 and 136-146 of SEQ ID NO: 2 of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising or present in residues 24-36, 54-65 and 100-102 of SEQ ID NO: 2 of human VISTA. In certain embodiments, the Ab binds to a conformational epitope comprising amino acid residues in the FG loop of human VISTA. In some embodiments, the Ab binds to a polypeptide comprising amino acid residues 35-127 and / or 37-125 of SEQ ID NO: 2.In some embodiments, 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 (polyptide) comprising an amino acid substitution, and substitution (1) is 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 of SEQ ID NO:2, or (2) is one of the following amino acid residues: Y37, T39, R54, F62, Q63, H66, L115, V117, I119, S124 or E125. In some embodiments, the anti-VISTA antibody has the same binding characteristics (or substantially the same binding characteristics) as the antibodies described herein, such as those shown in the Examples and / or in the claims.

[0056] Some of the above antibodies may exhibit differential binding affinity for the VISTA-ECD protein depending on pH. Certain Abs that specifically bind to the VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or below, 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 bind to the VISTA-ECD protein with a K D at pH 6.5 that is within 1.5-fold of the K D at pH 7.0, and bind at K -7 of 10 D M or less at both pH 6.5 and pH 7.0 (e.g., at a constant temperature of 25°C or 37°C). Some such Abs bind to the VISTA-ECD protein with a K D at pH 6.5 that is within 1.5-fold of the K D at pH 7.0, and bind at K -8 of 10 Dcan bind. Some such Abs bind to the hVISTA-ECD protein with a K at pH 6.5 that is within 1.5-fold of the K at pH 7.0. D is within 1.5-fold of the K at pH 7.0. D Both at pH 6.5 and at pH 7.0 (e.g., at a constant temperature of 25°C or 37°C), the K is 10 -8 M or less, and can bind. D

[0057] Certain Abs that specifically bind to the VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or less, can bind to the VISTA-ECD protein with a lower affinity under neutral, physiological, and / or alkaline conditions (a "pH-sensitive binder" or "pH-sensitive Ab"). Certain Abs that specifically bind to the VISTA-ECD protein under acidic conditions, e.g., at pH 6.5 or less, can have a binding that is not significant, e.g., almost undetectable, with the VISTA-ECD protein under neutral, physiological, and / or alkaline conditions. For example, in some embodiments, the Ab binds to the VISTA-ECD protein with a K of 10 -8 M or less at pH 6.5, and a K D greater than 10 -8 M at pH 7.0 and / or pH 7.4, and can bind. In some such embodiments, the Ab binds to the VISTA-ECD protein with a K of 10 D M or less at pH 6.5, and a K -8 greater than 1.5-fold that at pH 6.5 at pH 7.0 and / or pH 7.4, and can bind. In certain embodiments, the K with the VISTA-ECD protein at pH 6.5 is 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 that at pH 7.0. D D DThere is provided a pH-sensitive Ab that specifically binds at (for example, at a constant temperature of 25° C. or 37° C.). For example, in some cases, the Ab has 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 or 5000-fold lower than that at pH 7.0 and / or pH 7.4 with respect to the VISTA-ECD protein at pH 6.0 D and binds at (for example, at a constant temperature of 25° C. or 37° C.).

[0058] In certain embodiments, the Ab specifically binds to the VISTA-ECD protein with a lower k under acidic conditions compared to that under neutral, physiological or alkaline conditions. off In certain embodiments, the Ab specifically binds to the VISTA-ECD protein with a k at pH 6.5 that is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1000-fold lower than the k at pH 7.0 and / or pH 7.4 as measured, for example, at 25° C. or 37° C. off There is provided an Ab that binds with a k that 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 with respect to the VISTA-ECD protein at pH 6.0. In other words, the off-rate is slower at acidic pH than at neutral pH. For example, in some embodiments, the Ab has a k that 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 with respect to the VISTA-ECD protein at pH 6.0 as measured, for example, at 25° C. or 37° C. off There is provided an Ab that binds at a rate that 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 7.4 with respect to the VISTA-ECD protein at pH 6.5 as measured, for example, at 25° C. or 37° C. In certain embodiments, the Ab has a k that 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 7.4 with respect to the VISTA-ECD protein at pH 6.0 as measured, for example, at 25° C. or 37° C. off There is provided an Ab that binds with a k that 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 7.4 with respect to the VISTA-ECD protein at pH 6.5 as measured, for example, at 25° C. or 37° C. In some embodiments, the Ab has a k that 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 7.4 with respect to the VISTA-ECD protein at pH 6.0 as measured, for example, at 25° C. or 37° C. off There is provided an Ab that binds with a k that 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 7.4 with respect to the VISTA-ECD protein at pH 6.0 as measured, for example, at 25° C. or 37° C. off In some embodiments, the Ab has a k that 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 7.4 with respect to the VISTA-ECD protein at pH 6.0 as measured, for example, at 25° C. or 37° C. offBinds specifically with speed. In certain embodiments, the VISTA-ECD protein and, for example, at 25 °C or as measured at 37 °C, at pH 6.0 - 6.5, k at pH 7.0 - 7.4 off Is at least 1.5-fold, 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1000-fold lower than k off To provide an Ab that binds with.

[0059] In certain embodiments, the VISTA-ECD protein and, under acidic conditions, has a higher k relative to neutral, physiological, or alkaline conditions on An Ab that binds specifically with. In certain embodiments, the VISTA-ECD protein and, under acidic conditions, for example, at 25 °C or as measured at 37 °C, at pH 6.5, k at pH 7.0 and / or pH 7.4 on Is at least 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1000-fold higher than k on To provide an Ab that binds with. For example, in some embodiments, the Ab has a k that is at least 2-fold, 5-fold, 10-fold, 20-fold, 50-fold, 100-fold or 1000-fold higher than at pH 6.0 compared to the aVISTA-ECD protein at pH 7.0 and / or pH 7.4 as measured at 25 °C or 37 °C on Binds specifically with.

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

[0061] Also included herein are VISTA-ECD proteins and Abs that specifically bind with high affinity to acidic pH and, as long as the affinity of the binding at acidic pH remains high, also bind with high affinity specifically to acidic pH at neutral, physiological, or alkaline pH. For example, the Ab binds at pH 7.0 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 than that at pH 6.5 D but the Ab binds with the VISTA-ECD protein at both pH 6.5 and pH 7.0 with a K -8 of 10 D M or less.

[0062] Also included herein are Abs that share one or more of the above-described properties of this section. The above-described properties, e.g., the individual K D , k off , k on , specific epitope should not be treated in isolation. Thus, the Ab can bind to an epitope that includes one of the regions of SEQ ID NO: 2 above and also has pan-binding or pH-sensitive or pH-selective binding properties as described above, as indicated by one or more of the behaviors of its K D , k off or k on at different pHs.

[0063] In any of the above embodiments, the Ab can be, for example, a full-length antibody [i.e., including 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, an Fv fragment, or the Ab can be a chimeric, humanized, or human antibody, or the Ab can be a bispecific or multispecific antibody.

[0064] Determining how well Ab binds to VISTA-ECD protein at a given pH can be carried out using several different methods. For example, by surface plasmon resonance (SPR), such as by a BIACORE® assay. An exemplary SPR assay involves capturing one or several antibodies on a CM4 sensor chip using an immobilized capture reagent (e.g., using a Biacore® anti-human Fc capture kit, GE Healthcare catalog number BR-1008-39 or a Biacore® anti-mouse capture kit, GE Healthcare catalog number BR-1008-39) and flowing VISTA antigen as a concentration series of analytes to determine the binding kinetics and affinity in a running buffer having the desired pH. In one embodiment, VISTA is injected at a flow rate of 30 μL / min at 2-5 concentrations in the range of 0.1 nM to 500 nM (e.g., 0.1 nM, 1 nM, 10 nM, 100 nM, 500 nM) for a maximum association time of 4 minutes and a maximum dissociation time of 10 minutes. During the binding cycle, the capture surface is regenerated according to the manufacturer's instructions for each capture kit. All data are double-referenced using a reference flow cell and blank injection. Data with simple 1:1 kinetics are fit to a Langmuir binding model with mass transfer using Biacore® T200 evaluation software. The SPR method described in the examples can also be used.

[0065] The affinity of an Ab for a VISTA ECD polypeptide can be determined using cells expressing the VISTA ECD polypeptide, PSGL-1, or heparan sulfate on their surface, and this method includes flow cytometry and can determine the binding of the Ab to the VISTA-ECD bound to the cells at a given pH, for example, pH 6.5 or less. Exemplary flow cytometry assays include: resuspending 293T cells or other cells heterologously expressing hVISTA ECD in a buffer consisting of HBSS + 1% BSA adjusted to the desired pH, for example, pH 6.0 using MES or pH 7.4 using HEPES. The Ab (e.g., human IgG) against hVISTA is serially diluted from approximately 20 μg / mL and incubated with the resuspended cells at 4° C. for 30 minutes. Then, while maintaining the desired pH, for example, pH 6.0 or 7.4, the cells are washed twice with the same buffer and incubated with a secondary antibody conjugated to a fluorophore that recognizes the primary antibody (e.g., human IgG) and is stable at reduced pH. The cells are then washed as before and immediately acquired on a BD Fortessa or other flow cytometer without fixation. The affinity of the Ab for the VISTA ECD polypeptide can be determined as described in the examples.

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

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

[0068] The VISTA binding partner can be PSGL-1, e.g., human PSGL-1. The sequences of human PSGL-1 isoforms are provided herein as SEQ ID NOs: 3-10. VISTA binds to PSGL-1 with or without sialyl lewis X. The binding partner can also be, e.g., a heparan sulfate proteoglycan present on certain cells.

[0069] Inhibition of the binding of VISTA to its binding partner can be determined by measuring the inhibition of the binding of VISTA (or VISTA ECD or VISTA IgV domain or VISTA-positive cells) to cells to which VISTA binds, such as T cells (e.g., CD4+ T cells, CD8+ T cells, either activated or not activated), NK cells or other cells to which VISTA binds, in the presence and absence of an antibody. Exemplary experiments that can be used to examine whether the binding of VISTA to its binding partner or to T cells expressing the binding partner is inhibited are flow cytometry assays, such as assays that include: human peripheral blood mononuclear cells, buffy coat or leukopak obtained from donor blood are resuspended in a buffer consisting of HBSS + 1% BSA adjusted to pH 6.0 with, for example, MES and to pH 7.4 with HEPES. The cells are then incubated at 4° C. for 30 minutes with 20 μg / mL of a recombinant chimeric protein consisting of hVISTA ECD fused to human IgG1 Fc (VISTA-Fc) and with varying concentrations of a candidate VISTA blocking antibody or a control antibody. The cells are then washed twice with the same buffer while maintaining the desired pH, e.g., pH 6.0 or 7.4, and incubated at 4° C. for an additional 30 minutes with a secondary antibody conjugated to a fluorophore that recognizes VISTA-Fc but not the candidate blocking antibody or the control antibody and is stable at a reduced pH. The cells are then washed as before, not fixed, and immediately acquired on a BD Fortessa or other flow cytometer. Inhibition of binding can be determined, for example, as described in the Examples.

[0070] In certain embodiments, the Abs described herein can elicit or enhance an immune response, such as an antigen-specific immune response. In certain embodiments, the Abs specifically stimulate T cell activity, for example, at the acidic pH found, e.g., in the tumor microenvironment. Stimulation of T cell activity can be measured, for example, in a mixed lymphocyte reaction (MLR) or in an in vitro assay using antigen-presenting cells (natural or artificial) and T cells. Stimulation of T cell activity can also be measured, for example, using the Jurkat assay described in the Examples. Stimulation of T cell activity can also be measured, for example, as described in other Examples herein by measuring IFN-γ secretion from T cells, where an enhancement of IFN-γ secretion indicates T cell stimulation. Secretion of other cytokines from activated T cells can also be measured. In certain embodiments, signaling of activated T cells, such as NF-kB levels as described in the Examples, is measured.

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

[0072] The activity of the anti-VISTA Abs can also be shown, particularly, for example, at the acidic pH found in the tumor microenvironment, in monocyte assays, ADCC assays, and ADCP assays.

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

[0074] As shown in the Examples herein, recycling of anti-VISTA Ab in endosomes, for example to enhance the pharmacokinetic (PK) properties of the antibody, i.e., the half-life, requires the anti-VISTA antibody to bind VISTA under acidic conditions. Thus, an anti-VISTA Ab that binds VISTA at a low pH, e.g., a pH of 6.5 or less as further described herein, is also predicted to have a longer acceptable half-life compared to a VISTA antibody that does not bind VISTA at acidic pH.

[0075] Exemplary hVISTA-ECD binding Ab Provided herein are Abs that preferentially bind hVISTA(ECD) at an acidic pH (e.g., under acidic conditions) compared to physiological or neutral pH.

[0076] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain variable region ("VH") comprising any of the VH CDR1, CDR2, and / or CDR3 of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises a VH comprising any of the VH CDR1, CDR2, and CDR3 of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or its progeny, e.g., P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or the VH of another antibody disclosed in Example 17It comprises a VH comprising CDR1, CDR2 and / or CDR3. The VH CDR1, CDR2 and CDR3 of each of these species 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 antibody species provided in the following Sequence Listing. The CDRs are also underlined and in bold in each of the VH sequences of the above antibody species provided in the following Sequence Listing.

[0077] In certain embodiments, the anti-hVISTA Ab comprises a VL comprising any of the VL CDR1, CDR2, and CDR3 of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or the VH of another antibody disclosed in Example 17It includes a VL containing CDR1, CDR2 and CDR3. The VL CDR1, CDR2 and CDR3 of each of these species include amino acid positions 24 - 35 (VL CDR1), 51 - 57 (VL CDR2) and 90 - 98 (VL CDR3) of the VL sequences of each of the above antibody species provided in the following sequence listing. The CDRs are also underlined and in bold in each of these sequences.

[0078] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising any of the VH CDR1, CDR2, and / or CDR3 of the anti-hVISTA Abs provided herein and a VL comprising any of the CDR1, CDR2, and / or CDR3 of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises a VH comprising any of the VH CDR1, CDR2, and CDR3 of the anti-hVISTA Abs provided herein and a VL comprising any of the CDR1, CDR2, and CDR3 of any of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, such as P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, 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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22 to 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or the VH of another antibody disclosed in Example 17VH containing CDR1, CDR2 and / or CDR3 and P1-061029 or P1-061015 or its progeny, e.g., P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or a VL containing the VL CDR1, CDR2, and CDR3 of another antibody disclosed in Example 17.

[0079] In some embodiments, the anti-hVISTA Ab is (a) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-061029 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-061029, (b) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-061015 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-061015, (c) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068757 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068757, (d) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068759 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068759, (e) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068761, (f) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068763 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068763, (g) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068765 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068765, (h) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068767, (i) a VH comprising the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068769 and a VL comprising VL CDR1, CDR2, and CDR3 of P1-068769, (j) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068771, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-068771, (k) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068773, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-068773, (l) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068775, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-068775, (m) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069059, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069059, (n) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069061, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069061, (o) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069063, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069063, (p) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069065, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069065, (q) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069067, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069067, (r) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069069, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069069, (s) A VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069071, and a VL containing the VL CDR1, CDR2, and CDR3 of P1-069071, (t)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069073 and VL containing the VL CDR1, CDR2, and CDR3 of P1-069073, (u)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069075 and VL containing the VL CDR1, CDR2, and CDR3 of P1-069075, (v)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-069077 and VL containing the VL CDR1, CDR2, and CDR3 of P1-069077, (w)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068736 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068736, (x)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068738 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068738, (y)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068740 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068740, (z)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068742 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068742, (aa)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068744 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068744, (bb)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068746 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068746, (cc)VH containing the amino acid sequences of the VH CDR1, CDR2, and CDR3 of P1-068748 and VL containing the VL CDR1, CDR2, and CDR3 of P1-068748, (dd)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068750 and VL containing VL CDR1, CDR2 and CDR3 of P1-068750, (ee)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068752 and VL containing VL CDR1, CDR2 and CDR3 of P1-068752, (ff)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068754 and VL containing VL CDR1, CDR2 and CDR3 of P1-068754, (gg)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_E55A and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_E55A, (hh)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_H100G and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_H100G, (ii)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_E56N and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_E56N, (jj)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_E55A_E56N and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_E55A_E56N, (kk)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_E30D and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_E30D, (ll)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068761_E30D_E55A and VL containing VL CDR1, CDR2 and CDR3 of P1-068761_E30D_E55A, (mm)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E56N_H100G, (nn)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E30D_H100G, (oo)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E56N, (pp)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E100fF, (qq)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E55A_E100fF, (rr)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_H100G_E100fF, (ss)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E30D_E100fF, (tt)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068761_E56N_E100fF, (uu)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y, (vv)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y_E55A and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y_E55A, (ww)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y_E56N and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y_E56N, (xx)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E30D_E32Y and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E30D_E32Y, (yy)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y_H100G and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y_H100G, (zz)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068761_E32Y_E100fF and VL containing the VL CDR1, CDR2 and CDR3 of P1-068761_E32Y_E100fF, (aaa)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068767_D52N_D102V and VL containing the VL CDR1, CDR2 and CDR3 of P1-068767_D52N_D102V, (bbb)VH containing the amino acid sequences of the VH CDR1, CDR2 and CDR3 of P1-068767_D52N and VL containing the VL CDR1, CDR2 and CDR3 of P1-068767_D52N, (ccc)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_D52N_E55A and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_D52N_E55A, (ddd)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E55A_D102V and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E55A_D102V, (eee)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_D102V and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_D102V, (fff)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E55A and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E55A, (ggg)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E30D_D52N and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E30D_D52N, (hhh)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E30D_D102V and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E30D_D102V, (iii)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E30D and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E30D, (jjj)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-068767_E30D_E55A and VL containing VL CDR1, CDR2 and CDR3 of P1-068767_E30D_E55A, (kkk)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V and VL containing VL CDR1, CDR2, and CDR3 of P1-068767_E100fF_D102V, (lll)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068767_E55A_E100fF, (mmm)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068767_D52N_E100fF, (nnn)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068767_E100fF, (ooo)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-068767_E30D_E100fF and VL containing VL CDR1, CDR2, and CDR3 of P1-068767_E30D_E100fF, (ppp)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of VISTA.4 and VL containing VL CDR1, CDR2, and CDR3 of VISTA.4, (qqq)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of VISTA.4_VL_A64G and VL containing VL CDR1, CDR2, and CDR3 of VISTA.4_VL_A64G, (rrr)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-070976 and VL containing VL CDR1, CDR2, and CDR3 of P1-070976, (sss)VH containing the amino acid sequences of VH CDR1, CDR2, and CDR3 of P1-071799 and VL containing VL CDR1, CDR2, and CDR3 of P1-071799, (ttt)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-071801 and VL containing VL CDR1, CDR2 and CDR3 of P1-P1-071801, (uuu)VH containing the amino acid sequences of VH CDR1, CDR2 and CDR3 of P1-065333 and VL containing VL CDR1, CDR2 and CDR3 of P1-065333 may be included.

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

[0081] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising the amino acid sequence of any of the VHs of the anti-hVISTA Abs provided herein. The individual VH sequences of the specific antibody species provided herein are listed in the Sequence Listing. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, such as P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, 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, P1-068767_E30D_E100fF, or a VH comprising the amino acid sequence of a VH of an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22 to 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or a VH comprising the amino acid sequence of a VH of another antibody disclosed in Example 17.

[0082] In certain embodiments, the anti-hVISTA Ab comprises VH CDR1, CDR2, and CDR3 that include the amino acid sequences of any of the VH CDRs of the anti-hVISTA Abs 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 any of the VHs of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22 - 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4It comprises a VH comprising an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the amino acid sequence of the VH of VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17.

[0083] In certain embodiments, the anti-hVISTA Ab comprises a VH consisting of the amino acid sequence of any of the VHs of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, e.g., P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or a VH comprising an amino acid sequence of a VH of an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22 to 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or a VH comprising an amino acid sequence of a VH of another antibody disclosed in Example 17.

[0084] In certain embodiments, the anti-hVISTA Ab comprises a VL comprising the amino acid sequence of any of the VLs of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, for example, P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22 to 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or a VL containing the amino acid sequence of the VL of another antibody disclosed in Example 17.

[0085] In certain embodiments, the anti-hVISTA Ab comprises VL CDR1, CDR2, and CDR3 that include the amino acid sequences of any of the VL CDRs of the anti-hVISTA Abs 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 any of the VLs of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22 - 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4It comprises a VL that includes an amino acid sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the amino acid sequence of the VL of VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17.

[0086] In certain embodiments, the anti-hVISTA Ab comprises a VL consisting of the amino acid sequence of any of the VLs of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, such as, for example, P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22 to 30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or a VL comprising the amino acid sequence of the VL of another antibody disclosed in Example 17.

[0087] In certain embodiments, the anti-hVISTA Ab comprises a VH comprising the amino acid sequence of any of the VHs of the anti-hVISTA Abs provided herein, and a VL comprising the amino acid sequence of any of the VLs of the anti-hVISTA Abs provided herein. In certain ones of these embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, for example, 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, P1-068752VH containing the amino acid sequence of VH of P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, 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, and VL containing the amino acid sequence of VL of P1-061029 or P1-061015. In certain embodiments, anti-hVISTAAb is P1-061029 or P1-061015 or its progeny, for example, 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, P1-068752VH and VL containing VH and VL amino acid sequences of P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, 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 are included. In certain embodiments, VH and VL are antibodies derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, such as VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4It comprises the amino acid sequences of VH and VL of VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17.

[0088] In certain embodiments, the anti-hVISTA Ab comprises VH CDR1, CDR2, and CDR3 that include the amino acid sequences of any of the VH CDRs of the anti-hVISTA Abs provided herein and VL CDR1, CDR2, and CDR3 that include the amino acid sequences of any of the VL CDRs of the anti-hVISTA Abs provided herein, and also includes VH and VL that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical, respectively, to the corresponding VH and VL of any of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises all six CDRs of the anti-hVISTA Abs provided herein and is P1-061029 or P1-061015 or a progeny thereof, e.g., P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an anti-hVISTA such as an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or VH and VL of another antibody disclosed in Example 17Also included are 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, respectively, to the corresponding VH and VL of Ab.

[0089] In certain embodiments, the anti-hVISTA Ab comprises a VH and a VL consisting of the amino acid sequences of the VH and VL of any of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab is P1-061029 or P1-061015 or a progeny thereof, such as, for example, 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, P1-068752VH and VL comprising VH and VL consisting of the amino acid sequences of VH and VL of P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, 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. In certain embodiments, the amino acid sequences of VH and VL are each an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4It consists of the amino acid sequences of VH and VL of VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17.

[0090] The anti-hVISTA Ab is (a) VH containing the amino acid sequence of VH of P1-061029 and VL containing the amino acid sequence of VL of P1-061029, (b) VH containing the amino acid sequence of VH of P1-061015 and VL containing the amino acid sequence of VL of P1-061015, (c) VH containing the amino acid sequence of VH of P1-068757 and VL containing the amino acid sequence of VL of P1-068757, (d) VH containing the amino acid sequence of VH of P1-068759 and VL containing the amino acid sequence of VL of P1-068759, (e) VH containing the amino acid sequence of VH of P1-068761 and VL containing the amino acid sequence of VL of P1-068761, (f) VH containing the amino acid sequence of VH of P1-068763 and VL containing the amino acid sequence of VL of P1-068763, (g) VH containing the amino acid sequence of VH of P1-068765 and VL containing the amino acid sequence of VL of P1-068765, (h) VH containing the amino acid sequence of VH of P1-068767 and VL containing the amino acid sequence of VL of P1-068767, (i) VH containing the amino acid sequence of VH of P1-068769 and VL containing the amino acid sequence of VL of P1-068769, (j) VH containing the amino acid sequence of VH of P1-068771 and VL containing the amino acid sequence of VL of P1-068771, (k) VH containing the amino acid sequence of VH of P1-068773 and VL containing the amino acid sequence of VL of P1-068773, (l) VH containing the amino acid sequence of VH of P1-068775 and VL containing the amino acid sequence of VL of P1-068775, (m)VH containing the amino acid sequence of VH of P1-069059 and VL containing the amino acid sequence of VL of P1-069059, (n)VH containing the amino acid sequence of VH of P1-069061 and VL containing the amino acid sequence of VL of P1-069061, (o)VH containing the amino acid sequence of VH of P1-069063 and VL containing the amino acid sequence of VL of P1-069063, (p)VH containing the amino acid sequence of VH of P1-069065 and VL containing the amino acid sequence of VL of P1-069065, (q)VH containing the amino acid sequence of VH of P1-069067 and VL containing the amino acid sequence of VL of P1-069067, (r)VH containing the amino acid sequence of VH of P1-069069 and VL containing the amino acid sequence of VL of P1-069069, (s)VH containing the amino acid sequence of VH of P1-069071 and VL containing the amino acid sequence of VL of P1-069071, (t)VH containing the amino acid sequence of VH of P1-069073 and VL containing the amino acid sequence of VL of P1-069073, (u)VH containing the amino acid sequence of VH of P1-069075 and VL containing the amino acid sequence of VL of P1-069075, (v)VH containing the amino acid sequence of VH of P1-069077 and VL containing the amino acid sequence of VL of P1-069077, (w)VH containing the amino acid sequence of VH of P1-068736 and VL containing the amino acid sequence of VL of P1-068736, (x)VH containing the amino acid sequence of VH of P1-068738 and VL containing the amino acid sequence of VL of P1-068738, (y)VH containing the amino acid sequence of VH of P1-068740 and VL containing the amino acid sequence of VL of P1-068740, (z)VH containing the amino acid sequence of VH of P1-068742 and VL containing the amino acid sequence of VL of P1-068742, (aa) VH containing the amino acid sequence of the VH of P1-068744 and VL containing the amino acid sequence of the VL of P1-068744, (bb) VH containing the amino acid sequence of the VH of P1-068746 and VL containing the amino acid sequence of the VL of P1-068746, (cc) VH containing the amino acid sequence of the VH of P1-068748 and VL containing the amino acid sequence of the VL of P1-068748, (dd) VH containing the amino acid sequence of the VH of P1-068750 and VL containing the amino acid sequence of the VL of P1-068750, (ee) VH containing the amino acid sequence of the VH of P1-068752 and VL containing the amino acid sequence of the VL of P1-068752, (ff) VH containing the amino acid sequence of the VH of P1-068754 and VL containing the amino acid sequence of the VL of P1-068754, (gg) VH containing the amino acid sequence of the VH of P1-068761_E55A and VL containing the amino acid sequence of the VL of P1-068761_E55A, (hh) VH containing the amino acid sequence of the VH of P1-068761_H100G and VL containing the amino acid sequence of the VL of P1-068761_H100G, (ii) VH containing the amino acid sequence of the VH of P1-068761_E56N and VL containing the amino acid sequence of the VL of P1-068761_E56N, (jj) VH containing the amino acid sequence of the VH of P1-068761_E55A_E56N and VL containing the amino acid sequence of the VL of P1-068761_E55A_E56N, (kk) VH containing the amino acid sequence of the VH of P1-068761_E30D and VL containing the amino acid sequence of the VL of P1-068761_E30D, (ll) VH containing the amino acid sequence of the VH of P1-068761_E30D_E55A and VL containing the amino acid sequence of the VL of P1-068761_E30D_E55A, (mm) VH containing the amino acid sequence of the VH of P1-068761_E56N_H100G and VL containing the amino acid sequence of the VL of P1-068761_E56N_H100G, (nn)VH containing the amino acid sequence of the VH of P1-068761_E30D_H100G and VL containing the amino acid sequence of the VL of P1-068761_E30D_H100G (oo)VH containing the amino acid sequence of the VH of P1-068761_E30D_E56N and VL containing the amino acid sequence of the VL of P1-068761_E30D_E56N (pp)VH containing the amino acid sequence of the VH of P1-068761_E100fF and VL containing the amino acid sequence of the VL of P1-068761_E100fF (qq)VH containing the amino acid sequence of the VH of P1-068761_E55A_E100fF and VL containing the amino acid sequence of the VL of P1-068761_E55A_E100fF (rr)VH containing the amino acid sequence of the VH of P1-068761_H100G_E100fF and VL containing the amino acid sequence of the VL of P1-068761_H100G_E100fF (ss)VH containing the amino acid sequence of the VH of P1-068761_E30D_E100fF and VL containing the amino acid sequence of the VL of P1-068761_E30D_E100fF (tt)VH containing the amino acid sequence of the VH of P1-068761_E56N_E100fF and VL containing the amino acid sequence of the VL of P1-068761_E56N_E100fF (uu)VH containing the amino acid sequence of the VH of P1-068761_E32Y and VL containing the amino acid sequence of the VL of P1-068761_E32Y (vv)VH containing the amino acid sequence of the VH of P1-068761_E32Y_E55A and VL containing the amino acid sequence of the VL of P1-068761_E32Y_E55A (ww)VH containing the amino acid sequence of the VH of P1-068761_E32Y_E56N and VL containing the amino acid sequence of the VL of P1-068761_E32Y_E56N (xx)VH containing the amino acid sequence of the VH of P1-068761_E30D_E32Y and VL containing the amino acid sequence of the VL of P1-068761_E30D_E32Y (yy)VH containing the amino acid sequence of the VH of P1-068761_E32Y_H100G and VL containing the amino acid sequence of the VL of P1-068761_E32Y_H100G, (zz)VH containing the amino acid sequence of the VH of P1-068761_E32Y_E100fF and VL containing the amino acid sequence of the VL of P1-068761_E32Y_E100fF, (aaa)VH containing the amino acid sequence of the VH of P1-068767_D52N_D102V and VL containing the amino acid sequence of the VL of P1-068767_D52N_D102V, (bbb)VH containing the amino acid sequence of the VH of P1-068767_D52N and VL containing the amino acid sequence of the VL of P1-068767_D52N, (ccc)VH containing the amino acid sequence of the VH of P1-068767_D52N_E55A and VL containing the amino acid sequence of the VL of P1-068767_D52N_E55A, (ddd)VH containing the amino acid sequence of the VH of P1-068767_E55A_D102V and VL containing the amino acid sequence of the VL of P1-068767_E55A_D102V, (eee)VH containing the amino acid sequence of the VH of P1-068767_D102V and VL containing the amino acid sequence of the VL of P1-068767_D102V, (fff)VH containing the amino acid sequence of the VH of P1-068767_E55A and VL containing the amino acid sequence of the VL of P1-068767_E55A, (ggg)VH containing the amino acid sequence of the VH of P1-068767_E30D_D52N and VL containing the amino acid sequence of the VL of P1-068767_E30D_D52N, (hhh)VH containing the amino acid sequence of the VH of P1-068767_E30D_D102V and VL containing the amino acid sequence of the VL of P1-068767_E30D_D102V, (iii)VH containing the amino acid sequence of the VH of P1-068767_E30D and VL containing the amino acid sequence of the VL of P1-068767_E30D, (jjj) VH containing the amino acid sequence of the VH of P1-068767_E30D_E55A and VL containing the amino acid sequence of the VL of P1-068767_E30D_E55A, (kkk) VH containing the amino acid sequence of the VH of P1-068767_E100fF_D102V and VL containing the amino acid sequence of the VL of P1-068767_E100fF_D102V, (lll) VH containing the amino acid sequence of the VH of P1-068767_E55A_E100fF and VL containing the amino acid sequence of the VL of P1-068767_E55A_E100fF, (mmm) VH containing the amino acid sequence of the VH of P1-068767_D52N_E100fF and VL containing the amino acid sequence of the VL of P1-068767_D52N_E100fF, (nnn) VH containing the amino acid sequence of the VH of P1-068767_E100fF and VL containing the amino acid sequence of the VL of P1-068767_E100fF, or (ooo) VH containing the amino acid sequence of the VH of P1-068767_E30D_E100fF and VL containing the amino acid sequence of the VL of P1-068767_E30D_E100fF, (ppp) VH containing the amino acid sequence of the VH of VISTA.4 and VL containing VL of VISTA.4, (qqq) VH containing the amino acid sequence of the VH of VISTA.4_VL_A64G and VL containing VL of VISTA.4_VL_A64G, (rrr) VH containing the amino acid sequence of the VH of P1-070976 and VL containing VL of P1-070976, (sss) VH containing the amino acid sequence of the VH of P1-071799 and VL containing VL of P1-071799, (ttt) VH containing the amino acid sequence of the VH of P1-071801 and VL containing VL of P1-P1-071801, (uuu) VH containing the amino acid sequence of the VH of P1-065333 and VL containing VL of P1-065333 may be included.

[0091] The anti-hVISTA Ab is, (a) VH and VL amino acid sequences that contain the VH CDR of VH of P1-061029 and the VL CDR of VL of P1-061029 and 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, (b) VH and VL amino acid sequences that contain the VH CDR of VH of P1-061015 and the VL CDR of VL of P1-061015 and are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-061015, (c) VH and VL amino acid sequences that contain the VH CDR of VH of P1-068757 and the VL CDR of VL of P1-068757 and 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, (d) VH and VL amino acid sequences that contain the VH CDR of VH of P1-068759 and the VL CDR of VL of P1-068759 and 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, (e) VH and VL amino acid sequences that contain the VH CDR of VH of P1-068761 and the VL CDR of VL of P1-068761 and 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, (f) VH amino acid sequences containing the VH CDR of P1-068763 and VL amino acid sequences containing the VL CDR 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, (g) VH amino acid sequences containing the VH CDR of P1-068765 and VL amino acid sequences containing the VL CDR 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, (h) VH amino acid sequences containing the VH CDR of P1-068767 and VL amino acid sequences containing the VL CDR 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, (i) VH amino acid sequences containing the VH CDR of P1-068769 and VL amino acid sequences containing the VL CDR of P1-068769, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068769, (j) VH amino acid sequences containing the VH CDR of P1-068771 and VL amino acid sequences containing the VL CDR 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, (k)VH amino acid sequences containing the VH CDR of P1-068773 and VL amino acid sequences containing the VL CDR 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, (l)VH amino acid sequences containing the VH CDR of P1-068775 and VL amino acid sequences containing the VL CDR 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, (m)VH amino acid sequences containing the VH CDR of P1-069059 and VL amino acid sequences containing the VL CDR 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, (n)VH amino acid sequences containing the VH CDR of P1-069061 and VL amino acid sequences containing the VL CDR 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, (o)VH amino acid sequences containing the VH CDR of P1-069063 and VL amino acid sequences containing the VL CDR 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, (p)VH amino acid sequences containing the VH CDR of P1-069065 and VL amino acid sequences containing the VL CDR 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, (q)VH amino acid sequences containing the VH CDR of P1-069067 and VL amino acid sequences containing the VL CDR 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, (r)VH amino acid sequences containing the VH CDR of P1-069069 and VL amino acid sequences containing the VL CDR 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, (s)VH amino acid sequences containing the VH CDR of P1-069071 and VL amino acid sequences containing the VL CDR of P1-069071, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-069071, (t)VH amino acid sequences containing the VH CDR of P1-069073 and VL amino acid sequences containing the VL CDR 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, (u) VH amino acid sequences containing the VH CDR of P1-069075 and VL amino acid sequences containing the VL CDR 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, (v) VH amino acid sequences containing the VH CDR of P1-069077 and VL amino acid sequences containing the VL CDR of P1-069077, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-069077, (w) VH amino acid sequences containing the VH CDR of P1-068736 and VL amino acid sequences containing the VL CDR 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, (x) VH amino acid sequences containing the VH CDR of P1-068738 and VL amino acid sequences containing the VL CDR of P1-068738, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068738, (y) VH amino acid sequences containing the VH CDR of P1-068740 and VL amino acid sequences containing the VL CDR 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, (z)VH amino acid sequences containing the VH CDR of VH of P1-068742 and VL amino acid sequences containing the VL CDR of VL 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, (aa)VH amino acid sequences containing the VH CDR of VH of P1-068744 and VL amino acid sequences containing the VL CDR of VL 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, (bb)VH amino acid sequences containing the VH CDR of VH of P1-068746 and VL amino acid sequences containing the VL CDR of VL 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, (cc)VH amino acid sequences containing the VH CDR of VH of P1-068748 and VL amino acid sequences containing the VL CDR of VL of P1-068748, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068748, (dd)VH amino acid sequences containing the VH CDR of P1-068750 and VL amino acid sequences containing the VL CDR 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, (ee)VH amino acid sequences containing the VH CDR of P1-068752 and VL amino acid sequences containing the VL CDR of P1-068752, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068752, (ff)VH amino acid sequences containing the VH CDR of P1-068754 and VL amino acid sequences containing the VL CDR of P1-068754, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068754, (gg)VH amino acid sequences containing the VH CDR of P1-068761_E55A and VL amino acid sequences containing the VL CDR of P1-068761_E55A, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E55A, (hh)VH containing the VH CDR of P1-068761_H100G and VL containing the VL CDR of P1-068761_H100G, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_H100G, (ii)VH containing the VH CDR of P1-068761_E56N and VL containing the VL CDR of P1-068761_E56N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E56N, (jj)VH containing the VH CDR of P1-068761_E55A_E56N and VL containing the VL CDR of P1-068761_E55A_E56N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E55A_E56N, (kk)VH containing the VH CDR of P1-068761_E30D and VL containing the VL CDR of P1-068761_E30D, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D, (ll)VH containing the VH CDR of P1-068761_E30D_E55A and VL containing the VL CDR of P1-068761_E30D_E55A, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D_E55A, (mm)VH containing the VH CDR of P1-068761_E56N_H100G and VL containing the VL CDR of P1-068761_E56N_H100G, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E56N_H100G, (nn)VH containing the VH CDR of P1-068761_E30D_H100G and VL containing the VL CDR of P1-068761_E30D_H100G, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D_H100G, (oo)VH containing the VH CDR of P1-068761_E30D_E56N and VL containing the VL CDR of P1-068761_E30D_E56N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D_E56N, (pp)VH containing the VH CDR of P1-068761_E100fF and VL containing the VL CDR of P1-068761_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E100fF, (qq)VH containing the VH CDR of P1-068761_E55A_E100fF and VL containing the VL CDR of P1-068761_E55A_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E55A_E100fF, (rr)VH containing the VH CDR of P1-068761_H100G_E100fF and VL containing the VL CDR 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, (ss)VH containing the VH CDR of P1-068761_E30D_E100fF and VL containing the VL CDR of P1-068761_E30D_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D_E100fF, (tt)VH containing the VH CDR of P1-068761_E56N_E100fF and VL containing the VL CDR 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, (uu)VH containing the VH CDR of P1-068761_E32Y and VL containing the VL CDR of P1-068761_E32Y, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E32Y, (vv)VH containing the VH CDR of P1-068761_E32Y_E55A and VL containing the VL CDR 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, (ww)VH containing the VH CDR of P1-068761_E32Y_E56N and VL containing the VL CDR of P1-068761_E32Y_E56N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E32Y_E56N, (xx)VH containing the VH CDR of P1-068761_E30D_E32Y and VL containing the VL CDR of P1-068761_E30D_E32Y, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E30D_E32Y, (yy)VH containing the VH CDR of P1-068761_E32Y_H100G and VL containing the VL CDR of P1-068761_E32Y_H100G, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E32Y_H100G, (zz)VH containing the VH CDR of P1-068761_E32Y_E100fF and VL containing the VL CDR of P1-068761_E32Y_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068761_E32Y_E100fF, (aaa)VH containing the VH CDR of P1-068767_D52N_D102V and VL containing the VL CDR of P1-068767_D52N_D102V, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_D52N_D102V, (bbb)VH containing the VH CDR of P1-068767_D52N and VL containing the VL CDR of P1-068767_D52N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_D52N, (ccc)VH containing the VH CDR of P1-068767_D52N_E55A and VL containing the VL CDR of P1-068767_D52N_E55A, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_D52N_E55A, (ddd)VH containing the VH CDR of P1-068767_E55A_D102V and VL containing the VL CDR of P1-068767_E55A_D102V, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E55A_D102V, (eee)VH containing the VH CDR of P1-068767_D102V and VL containing the VL CDR of P1-068767_D102V, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_D102V, (fff)VH containing the VH CDR of VH of P1-068767_E55A and VL containing the VL CDR of VL of P1-068767_E55A, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E55A, (ggg)VH containing the VH CDR of VH of P1-068767_E30D_D52N and VL containing the VL CDR of VL of P1-068767_E30D_D52N, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E30D_D52N, (hhh)VH containing the VH CDR of VH of P1-068767_E30D_D102V and VL containing the VL CDR of VL of P1-068767_E30D_D102V, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E30D_D102V, (iii)VH containing the VH CDR of VH of P1-068767_E30D and VL containing the VL CDR of VL of P1-068767_E30D, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E30D, (jjj)VH containing the VH CDR of P1-068767_E30D_E55A and VL containing the VL CDR of P1-068767_E30D_E55A, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E30D_E55A, (kkk)VH containing the VH CDR of P1-068767_E100fF_D102V and VL containing the VL CDR of P1-068767_E100fF_D102V, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E100fF_D102V, (lll)VH containing the VH CDR of P1-068767_E55A_E100fF and VL containing the VL CDR of P1-068767_E55A_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_E55A_E100fF, (mmm)VH containing the VH CDR of P1-068767_D52N_E100fF and VL containing the VL CDR of P1-068767_D52N_E100fF, and VH and VL amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the VH and VL of P1-068767_D52N_E100fF, (nnn)VH containing the VH CDR of P1-068767_E100fF and VL containing the VL CDR 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 (ooo)VH containing the VH CDR of P1-068767_E30D_E100fF and VL containing the VL CDR 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, (ppp)VH containing the VH CDR of VISTA.4 and VL containing the VL CDR of VISTA.4, 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 VISTA.4, (qqq)VH containing the VH CDR of VISTA.4_VL_A64G and VL containing the VL CDR of VISTA.4_VL_A64G, 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 VISTA.4_VL_A64G, (rrr)VH containing the VH CDR of P1-070976 and VL containing the VL CDR of P1-070976, 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 P1-070976, (sss)VH containing the VH CDR of P1-071799 and VL containing the VL CDR of P1-071799, 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 P1-071799, (ttt)VH containing the VH CDR of P1-071801 and VL containing the VL CDR of P1-071801, 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 P1-071801, or (uuu)VH containing the VH CDR of P1-065333 and VL containing the VL CDR of P1-065333, 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 P1-071799 may include.

[0092] The anti-hVISTA Ab is (a) VH consisting of the amino acid sequence of the VH of P1-061029 and VL consisting of the VL of P1-061029, (b) VH consisting of the amino acid sequence of the VH of P1-061015 and VL consisting of the VL of P1-061015, (c) VH consisting of the amino acid sequence of VH of P1-068757 and VL consisting of VL of P1-068757, (d) VH consisting of the amino acid sequence of VH of P1-068759 and VL consisting of VL of P1-068759, (e) VH consisting of the amino acid sequence of VH of P1-068761 and VL consisting of VL of P1-068761, (f) VH consisting of the amino acid sequence of VH of P1-068763 and VL consisting of VL of P1-068763, (g) VH consisting of the amino acid sequence of VH of P1-068765 and VL consisting of VL of P1-068765, (h) VH consisting of the amino acid sequence of VH of P1-068767 and VL consisting of VL of P1-068767, (i) VH consisting of the amino acid sequence of VH of P1-068769 and VL consisting of VL of P1-068769, (j) VH consisting of the amino acid sequence of VH of P1-068771 and VL consisting of VL of P1-068771, (k) VH consisting of the amino acid sequence of VH of P1-068773 and VL consisting of VL of P1-068773, (l) VH consisting of the amino acid sequence of VH of P1-068775 and VL consisting of VL of P1-068775, (m) VH consisting of the amino acid sequence of VH of P1-069059 and VL consisting of VL of P1-069059, (n) VH consisting of the amino acid sequence of VH of P1-069061 and VL consisting of VL of P1-069061, (o) VH consisting of the amino acid sequence of VH of P1-069063 and VL consisting of VL of P1-069063, (p) VH consisting of the amino acid sequence of VH of P1-069065 and VL consisting of VL of P1-069065, (q) VH consisting of the amino acid sequence of VH of P1-069067 and VL consisting of VL of P1-069067, VH consisting of the amino acid sequence of VH of (r)P1-069069 and VL consisting of VL of P1-069069, VH consisting of the amino acid sequence of VH of (s)P1-069071 and VL consisting of VL of P1-069071, VH consisting of the amino acid sequence of VH of (t)P1-069073 and VL consisting of VL of P1-069073, VH consisting of the amino acid sequence of VH of (u)P1-069075 and VL consisting of VL of P1-069075, VH consisting of the amino acid sequence of VH of (v)P1-069077 and VL consisting of VL of P1-069077, VH consisting of the amino acid sequence of VH of (w)P1-068736 and VL consisting of VL of P1-068736, VH consisting of the amino acid sequence of VH of (x)P1-068738 and VL consisting of VL of P1-068738, VH consisting of the amino acid sequence of VH of (y)P1-068740 and VL consisting of VL of P1-068740, VH consisting of the amino acid sequence of VH of (z)P1-068742 and VL consisting of VL of P1-068742, VH consisting of the amino acid sequence of VH of (aa)P1-068744 and VL consisting of VL of P1-068744, VH consisting of the amino acid sequence of VH of (bb)P1-068746 and VL consisting of VL of P1-068746, VH consisting of the amino acid sequence of VH of (cc)P1-068748 and VL consisting of VL of P1-068748, VH consisting of the amino acid sequence of VH of (dd)P1-068750 and VL consisting of VL of P1-068750, VH consisting of the amino acid sequence of VH of (ee)P1-068752 and VL consisting of VL of P1-068752, VH consisting of the amino acid sequence of VH of (ff)P1-068754 and VL consisting of VL of P1-068754, (gg) VH consisting of the amino acid sequence of the VH of P1-068761_E55A and VL consisting of the amino acid sequence of the VL of P1-068761_E55A, (hh) VH consisting of the amino acid sequence of the VH of P1-068761_H100G and VL consisting of the amino acid sequence of the VL of P1-068761_H100G, (ii) VH consisting of the amino acid sequence of the VH of P1-068761_E56N and VL consisting of the amino acid sequence of the VL of P1-068761_E56N, (jj) VH consisting of the amino acid sequence of the VH of P1-068761_E55A_E56N and VL consisting of the amino acid sequence of the VL of P1-068761_E55A_E56N, (kk) VH consisting of the amino acid sequence of the VH of P1-068761_E30D and VL consisting of the amino acid sequence of the VL of P1-068767_068761_E30D, (ll) VH consisting of the amino acid sequence of the VH of P1-068761_E30D_E55A and VL consisting of the amino acid sequence of the VL of P1-068761_E30D_E55A, (mm) VH consisting of the amino acid sequence of the VH of P1-068761_E56N_H100G and VL consisting of the amino acid sequence of the VL of P1-068761_E56N_H100G, (nn) VH consisting of the amino acid sequence of the VH of P1-068761_E30D_H100G and VL consisting of the amino acid sequence of the VL of P1-068761_E30D_H100G, (oo) VH consisting of the amino acid sequence of the VH of P1-068761_E30D_E56N and VL consisting of the amino acid sequence of the VL of P1-068761_E30D_E56N, (pp) VH consisting of the amino acid sequence of the VH of P1-068761_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_E100fF, (qq) VH consisting of the amino acid sequence of the VH of P1-068761_E55A_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_E55A_E100fF, (rr)VH consisting of the amino acid sequence of the VH of P1-068761_H100G_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_H100G_E100fF, (ss)VH consisting of the amino acid sequence of the VH of P1-068761_E30D_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_E30D_E100fF, (tt)VH consisting of the amino acid sequence of the VH of P1-068761_E56N_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_E56N_E100fF, (uu)VH consisting of the amino acid sequence of the VH of P1-068761_E32Y and VL consisting of the amino acid sequence of the VL of P1-068761_E32Y, (vv)VH consisting of the amino acid sequence of the VH of P1-068761_E32Y_E55A and VL consisting of the amino acid sequence of the VL of P1-068761_E32Y_E55A, (ww)VH consisting of the amino acid sequence of the VH of P1-068761_E32Y_E56N and VL consisting of the amino acid sequence of the VL of P1-068761_E32Y_E56N, (xx)VH consisting of the amino acid sequence of the VH of P1-068761_E30D_E32Y and VL consisting of the amino acid sequence of the VL of P1-068761_E30D_E32Y, (yy)VH consisting of the amino acid sequence of the VH of P1-068761_E32Y_H100G and VL consisting of the amino acid sequence of the VL of P1-068761_E32Y_H100G, (zz)VH consisting of the amino acid sequence of the VH of P1-068761_E32Y_E100fF and VL consisting of the amino acid sequence of the VL of P1-068761_E32Y_E100fF, (aaa)VH consisting of the amino acid sequence of the VH of P1-068767_D52N_D102V and VL consisting of the amino acid sequence of the VL of P1-068767_D52N_D102V, (bbb)VH consisting of the amino acid sequence of the VH of P1-068767_D52N and VL consisting of the amino acid sequence of the VL of P1-068767_D52N, (ccc)VH consisting of the amino acid sequence of the VH of P1-068767_D52N_E55A and VL consisting of the amino acid sequence of the VL of P1-068767_D52N_E55A, (ddd)VH consisting of the amino acid sequence of the VH of P1-068767_E55A_D102V and VL consisting of the amino acid sequence of the VL of P1-068767_E55A_D102V, (eee)VH consisting of the amino acid sequence of the VH of P1-068767_D102V and VL consisting of the amino acid sequence of the VL of P1-068767_D102V, (fff)VH consisting of the amino acid sequence of the VH of P1-068767_E55A and VL consisting of the amino acid sequence of the VL of P1-068767_E55A, (ggg)VH consisting of the amino acid sequence of the VH of P1-068767_E30D_D52N and VL consisting of the amino acid sequence of the VL of P1-068767_E30D_D52N, (hhh)VH consisting of the amino acid sequence of the VH of P1-068767_E30D_D102V and VL consisting of the amino acid sequence of the VL of P1-068767_E30D_D102V, (iii)VH consisting of the amino acid sequence of the VH of P1-068767_E30D and VL consisting of the amino acid sequence of the VL of P1-068767_E30D, (jjj)VH consisting of the amino acid sequence of the VH of P1-068767_E30D_E55A and VL consisting of the amino acid sequence of the VL of P1-068767_E30D_E55A, (kkk)VH consisting of the amino acid sequence of the VH of P1-068767_E100fF_D102V and VL consisting of the amino acid sequence of the VL of P1-068767_E100fF_D102V, (lll)VH consisting of the amino acid sequence of the VH of P1-068767_E55A_E100fF and VL consisting of the amino acid sequence of the VL of P1-068767_E55A_E100fF, (mmm)VH consisting of the amino acid sequence of the VH of P1-068767_D52N_E100fF and VL consisting of the amino acid sequence of the VL of P1-068767_D52N_E100fF, VH consisting of the amino acid sequence of VH of (nnn)P1-068767_E100fF and VL consisting of the amino acid sequence of VL of P1-068767_E100fF, or VH consisting of the amino acid sequence of VH of (ooo)P1-068767_E30D_E100fF and VL consisting of the amino acid sequence of VL of P1-068767_E30D_E100fF, VH consisting of the amino acid sequence of VH of (ppp)VISTA.4 and VL consisting of VL of VISTA.4, VH consisting of the amino acid sequence of VH of (qqq)VISTA.4_VL_A64G and VL consisting of VL of VISTA.4_VL_A64G, VH consisting of the amino acid sequence of VH of (rrr)P1-070976 and VL consisting of VL of P1-070976, VH consisting of the amino acid sequence of VH of (sss)P1-071799 and VL consisting of VL of P1-071799, VH consisting of the amino acid sequence of VH of (ttt)P1-071801 and VL consisting of VL of P1-071801, or VH consisting of the amino acid sequence of VH of (uuu)P1-065333 and VL consisting of VL of P1-065333 may be included.

[0093] In certain embodiments, the anti-VISTA Ab is any of the variable regions and / or variable region CDR1-3 of the antibodies described above and elsewhere in this specification, for example, P1-061029, P1-068757, P1-068759, P1-068761, P1-068763, P1-068765, P1-068767, P1-068769, P1-068771, P1-068773, P1-068775, P1-069059, P1-069061, P1-069063, P1-069065, P1-069067, P1-069069, P1-069071, P1-069073, P1-069075, P1-069077, P1-061015, P1-068736, P1-068738, P1-068740, P1-068742, P1-068744, P1-068766, P1-068748, P1-068750, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17 (1)One or more of VH CDR1, CDR2, and CDR3, (2)VH CDR1, CDR2, and CDR3, (3)VH, (4)One or more of VH CDR1, CDR2, and CDR3 and one or more of VL CDR1, CDR2, and CDR3, (5)VH CDR1, CDR2, and CDR3 and VL CDR1, CDR2, and CDR3, or (6)VH and VL and the anti-VISTA Ab is also, as described in the following section, an IgG antibody, e.g., an IgG1, IgG2, IgG3, or IgG4 antibody or a modified form thereof. 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 of IgG1.3.

[0094] In certain embodiments, the anti-VISTA Ab is any of the variable regions and / or variable region CDR1-3 of the antibodies described above and elsewhere herein, 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, P1-068752P1-068754, P1-068761_E55A, P1-068761_H100G, P1-068761_E56N, P1-068761_E55A_E56N, P1-068761_E30D, P1-068761_E30D_E55A, P1-068761_E56N_H100G, P1-068761_E30D_H100G, P1-068761_E30D_E56N, P1-068761_E100fF, P1-068761_E55A_E100fF, P1-068761_H100G_E100fF, P1-068761_E30D_E100fF, P1-068761_E56N_E100fF, P1-068761_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, P1-068767_E30D_E100fF, or an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17 (1)One or more of VH CDR1, CDR2, and CDR3, (2)VH CDR1, CDR2, and CDR3, (3)VH, (4)One or more of VH CDR1, CDR2, and CDR3 and one or more of VL CDR1, CDR2, and CDR3, (5)VH CDR1, CDR2, and CDR3 and VL CDR1, CDR2, and CDR3, or (6)VH and VL comprising the following features: - Specifically binding to hVISTA, for example, a histidine-rich region of ECD or a polypeptide comprising amino acid residues 35 - 127 of SEQ ID NO: 2, at an acidic pH, such as pH 6.0 or pH 6.5; - Lacking significant binding to hVISTA, for example, a histidine-rich region of ECD or a polypeptide comprising amino acid residues 35 - 127 of SEQ ID NO: 2, at physiological pH or neutral pH, such as pH 7.4 or pH 7.0; - Specifically binding to cyno VISTA, for example, a histidine-rich region of ECD, at an acidic pH, such as pH 6.0 or pH 6.5; - Lacking significant binding to cyno VISTA, for example, a histidine-rich region of ECD, at physiological pH or neutral pH, such as pH 7.4 or pH 7.0; - Having a reduced binding to an hVISTA-ECD having substitutions with one or more of the following amino acids: T35, Y37, K38, T39, Y41, R54, T61, F62, Q63, L65, H66, L67, H68, H69, F97, L115, V117, I119, H121, H122, S124, E125, R127, as compared to hVISTA ECD having SEQ ID NO: 2; - Cross-competing with P1-061029, P1-068761, P1-068767, and / or P1-061015 for binding to hVISTA. - inhibiting the binding of hVISTA to human T cells expressing VISTA (e.g., naive or activated T cells) at acidic pH, e.g., pH 6.0 or pH 6.5, - inhibiting the binding of hVISTA to PSGL-1 with or without sialyl Lewis X at acidic pH, e.g., pH 6.0 or pH 6.5 (e.g., inhibiting the interaction between H153 and H154 of hVISTA having SEQ ID NO: 1 and tyrosine Y46 and Y48 of PSGL-1), wherein PSGL-1 has or does not have sialyl Lewis X and the tyrosine is preferably sulfotyrosine), - having an average residence time (MRT) of at least 100, 200, 300, 350, 400, 450, 500, 600 or 700 hours (e.g., at least 350 hours) in cynomolgus monkeys as measured, for example, as described in the examples, - stimulating T cell activation, for example, by enhancing T cell proliferation, enhancing IFN-γ production from T cells and / or stimulating T cell receptor-mediated NF-κB signaling, - inhibiting VISTA-mediated cell:cell adhesion, - specifically binding to hVISTA in a sample of human tumor cells or a sample of inflamed human tissue expressing VISTA, - contacting hVISTA by one or more (e.g., at least 1-3, 1-5, 1-10, 5-10, 5-15 or all) of the energetically important contact residues Y37, T39, R54, F62, H66, V117, I119 or S124 numbered as those of mature hVISTA as determined using, for example, yeast surface display and NGS assays as described in Example 15, - the binding to Region 2 may be the strongest as determined by MS-HDX as described in Example 18, Region 1 of hVISTA having SEQ ID NO: 1: 57 LGPVDKGHDVTF 68 (SEQ ID NO: 498), Region 2:86 RRPIRNLTFQDL 97 (SEQ ID NO: 497) and Region 3: 148 VVEIRHHHSEHRVHGAME 165 bind to (SEQ ID NO: 499), - for example, as described in the Examples, bind to the histidine-rich β-sheet extension of hVISTA, as determined, for example, by crystallography, - for example, as described in the Examples, contact (i) H121, H122 and / or H123 or (ii) H66, H68, H121, H122 and / or H123 (at a distance of 4.0 angstroms (Å) or less) of mature hVISTA, for example, by hydrogen bonding, as determined, for example, by crystallography, as described in the Examples, - contact hVISTA by at least one or more glutamic acid, aspartic acid or histidine residues located in VH CDR1, CDR2 or CDR3, - low or undetectable levels of TMDD, - low or undetectable levels of neutropenia, and - any further features shown in the claims and / or in the Examples further comprising one or more of.

[0095] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain (HC) comprising the amino acid sequence of any of the heavy chains of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises an IgG1.3 heavy chain constant region, e.g., P1-061029.IgG1.3 (SEQ ID NO: 69), P1-068757.IgG1.3, P1-068759.IgG1.3, P1-068761.IgG1.3, P1-068763.IgG1.3, P1-068765.IgG1.3, P1-068767.IgG1.3, P1-068769.IgG1.3, P1-068771.IgG1.3, P1-068773.IgG1.3, P1-068775.IgG1.3, P1-069059.IgG1.3, P1-069061.IgG1.3, P1-069063.IgG1.3, P1-069065.IgG1.3, P1-069067.IgG1.3, P1-069069.IgG1.3, P1-069071.IgG1.3, P1-069073.IgG1.3, P1-069075.IgG1.3, P1-069077.IgG1.3, P1-061015.IgG1.3, P1-068736.IgG1.3, P1-068738.IgG1.3, P1-068740.IgG1.3, P1-068742.IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1.3, P1-068752.IgG1.3, P1-068754.IgG1.3, 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.An antibody comprising a heavy chain comprising the amino acid sequence of the heavy chain of P1-061029 or P1-061015 or a progeny thereof as shown below in the Sequence Listing, comprising IgG1.3, P1-068761_E56N_E100fF.IgG1.3, P1-068761_E32Y.IgG1.3, 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_D102V.IgG1.3, P1-068767_D102V.IgG1.3, P1-068767_E55A.IgG1.3, P1-068767_E30D_D52N.IgG1.3, P1-068767_E30D_D102V.IgG1.3, P1-068767_E30D.IgG1.3, P1-068767_E30D_E55A.IgG1.3, 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. In certain embodiments, the antibody may comprise an IgG1.3 heavy chain constant region, an antibody derived from VISTA.4 (alias, 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or the heavy chain amino acid sequence of another antibody disclosed in Example 17.

[0096] In certain embodiments, the anti-hVISTA Ab comprises a heavy chain comprising the amino acid sequence of any of the heavy chains of the anti-hVISTA Abs provided herein that includes an IgG1.3 heavy chain constant region, and a light chain comprising the amino acid sequence of any of the light chains of the anti-hVISTA Abs provided herein. In certain embodiments, the anti-hVISTA Ab comprises 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, P1-069061.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, P1-068742.IgG1.3, P1-068744.IgG1.3, P1-068766.IgG1.3, P1-068748.IgG1.3, P1-068750.IgG1.3, P1-068752.IgG1.3, P1-068754.IgG1.3, P1-068761_E55A.IgG1.3, P1-068761_H100G.IgG1.3, P1-068761_E56N.IgG1.3, 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. Heavy chains containing the amino acid sequence of VH of P1-061029 or P1-061015 or its progeny, and light chains containing the amino acid sequence of the light chain of P1-061029 or P1-061015, including P1-068761_H100G_E100fF.IgG1.3, P1-068761_E30D_E100fF.IgG1.3, P1-068761_E56N_E100fF.IgG1.3, P1-068761_E32Y.IgG1.3, P1-068761_E32Y_E55A.IgG1.3, P1-068761_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_D102V.IgG1.3, P1-068767_D102V.IgG1.3, P1-068767_E55A.IgG1.3, P1-068767_E30D_D52N.IgG1.3, P1-068767_E30D_D102V.IgG1.3, P1-068767_E30D.IgG1.3, P1-068767_E30D_E55A.IgG1.3, 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. In certain embodiments, the antibody is an IgG1.3 antibody and, as the light chain of the same antibody, an antibody derived from VISTA.4 (also known as 41F11) described in Tables 22-30 of Example 17, for example, VISTA.4, VISTA.4_VL_A64G, P1-070976 (VISTA.4 VH_T28P, Y50W, S55E, D95H, L96E, P97E, Y100E; VL_A64G), P1-071799 (P1-070976_VH_H95D), P1-071801 (P1-070976_VH_E97P), or P1-065333 (VISTA.comprises a heavy chain of 4 VH_T28P, Y50W, S55E, L96E, Y100E; VL_A64G), or another antibody disclosed in Example 17.

[0097] The anti-hVISTA Ab is (a) a heavy chain comprising the amino acid sequence of the heavy chain of P1-061029.IgG1.3 (SEQ ID NO: 69) and a light chain comprising the light chain amino acid sequence of P1-061029 (SEQ ID NO: 70), (b) a heavy chain comprising the amino acid sequence of the heavy chain of P1-061015.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-061015, (c) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068757.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068757, (d) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068759.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068759, (e) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068761.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068761, (f) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068763.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068763, (g) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068765.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068765, (h) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068767.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068767, (i) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068769.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068769, (j) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068771.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068771, (k) a heavy chain comprising the amino acid sequence of the heavy chain of P1-068773.IgG1.3 and a light chain comprising the light chain amino acid sequence of P1-068773, (l) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068775.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068775, (m) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069059.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069059, (n) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069061.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069061, (o) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069063.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069063, (p) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069065.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069065, (q) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069067.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069067, (r) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069069.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069069, (s) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069071.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069071, (t) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069073.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069073, (u) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069075.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069075, (v) A heavy chain comprising the amino acid sequence of the heavy chain of P1-069077.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-069077, (w) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068736.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068736, (x) A heavy chain comprising the amino acid sequence of the heavy chain of P1-068738.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068738, (y)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068740.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068740, (z)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068742.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068742, (aa)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068744.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068744, (bb)A heavy chain comprising the amino acid sequence of the VH of P1-068746.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068746, (cc)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068748.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068748, (dd)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068750.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068750, (ee)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068752.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068752, (ff)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068754.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068754, (gg)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A, (hh)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_H100G.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G, (ii)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N, (jj)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A_E56N.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E56N, (kk)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D, (ll)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E55A, (mm)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N_H100G.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_H100G, (nn)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_H100G.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_H100G, (oo)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E56N.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E56N, (pp)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E100fF, (qq)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E55A_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E100fF, (rr)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_H100G_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G_E100fF, (ss)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E100fF, (tt)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E56N_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_E100fF, (uu)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y, (vv)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E55A, (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 amino acid sequence of the light chain of P1-068761_E32Y_E56N, (xx)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E30D_E32Y.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E32Y, (yy)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_H100G.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_H100G, (zz)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068761_E32Y_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E100fF, (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 amino acid sequence of the light chain of P1-068767_D52N_D102V, (bbb)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N, (ccc)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E55A, (ddd)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A_D102V.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_D102V, (eee)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D102V.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_D102V, (fff)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A, (ggg)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_D52N.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D52N, (hhh)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_D102V.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D102V, (iii)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D, (jjj)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_E55A.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E55A, (kkk)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E100fF_D102V.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF_D102V, (lll)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E55A_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_E100fF, (mmm)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_D52N_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E100fF, (nnn)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF, (ooo)A heavy chain comprising the amino acid sequence of the heavy chain of P1-068767_E30D_E100fF.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E100fF, (ppp)A heavy chain comprising the amino acid sequence of the heavy chain of VISTA.4.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of VISTA.4.IgG1.3, (qqq)A heavy chain comprising the amino acid sequence of the heavy chain of VISTA.4_VL_A64G.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of VISTA.4_VL_A64G.IgG1.3, (rrr)A heavy chain comprising the amino acid sequence of the heavy chain of P1-070976.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-070976.IgG1.3, (sss)A heavy chain comprising the amino acid sequence of the heavy chain of P1-071799.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-071799.IgG1.3, or (ttt)A heavy chain comprising the amino acid sequence of the heavy chain of P1-071801.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-071801.IgG1.3, (uuu)A heavy chain comprising the amino acid sequence of the heavy chain of P1-065333.IgG1.3 and a light chain comprising the amino acid sequence of the light chain of P1-065333.IgG1.3 may be included.

[0098] The anti-hVISTA Ab is (a) A heavy chain (HC) comprising the HC CDR of P1-061029 and a light chain (LC) comprising the LC CDR of P1-061029, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-061029.IgG1.3, respectively, (b) An HC comprising the HC CDR of the HC of P1-061015, an LC comprising the LC CDR 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, (c) An HC comprising the HC CDR of the HC of P1-068757, an LC comprising the LC CDR 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, (d) An HC comprising the HC CDR of the HC of P1-068759, an LC comprising the LC CDR 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, (e) An HC comprising the HC CDR of the HC of P1-068761, an LC comprising the LC CDR 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, (f) An HC comprising the HC CDR of the HC of P1-068763, an LC comprising the LC CDR 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, (g) An HC comprising the HC CDR of the HC of P1-068765, an LC comprising the LC CDR 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, (h) An HC comprising the HC CDR of the HC of P1-068767, an LC comprising the LC CDR 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, (i) An HC comprising the HC CDR of the HC of P1-068769, an LC comprising the LC CDR 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, (j) An HC containing the HC CDR of P1-068771's HC, an LC containing the LC CDR 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, (k) An HC containing the HC CDR of P1-068773's HC, an LC containing the LC CDR 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, (l) An HC containing the HC CDR of P1-068775's HC, an LC containing the LC CDR 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, (m) An HC containing the HC CDR of P1-069059's HC, an LC containing the LC CDR 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, (n) An HC containing the HC CDR of the HC of P1-069061, an LC containing the LC CDR 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, (o) An HC containing the HC CDR of the HC of P1-069063, an LC containing the LC CDR 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, (p) An HC containing the HC CDR of the HC of P1-069065, an LC containing the LC CDR 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, (q) An HC containing the HC CDR of the HC of P1-069067, an LC containing the LC CDR 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, (r) An HC containing the HC CDR of the HC of P1-069069, an LC containing the LC CDR 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, (s) An HC containing the HC CDR of the HC of P1-069071, an LC containing the LC CDR 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, (t) An HC containing the HC CDR of the HC of P1-069073, an LC containing the LC CDR 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, (u) An HC containing the HC CDR of the HC of P1-069075, an LC containing the LC CDR 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, (v) An HC comprising the HC CDR of the HC of P1-069077, an LC comprising the LC CDR 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, (w) An HC comprising the HC CDR of the HC of P1-068376, an LC comprising the LC CDR of P1-068376, 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 P1-068376.IgG1.3, respectively, (x) An HC comprising the HC CDR of the HC of P1-068738, an LC comprising the LC CDR 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, (y) An HC comprising the HC CDR of the HC of P1-068740, an LC comprising the LC CDR 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, (z) An HC containing the HC CDR of the HC of P1-068742, an LC containing the LC CDR 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, (aa) An HC containing the HC CDR of the HC of P1-068744, an LC containing the LC CDR 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, (bb) An HC containing the HC CDR of the HC of P1-068746, an LC containing the LC CDR 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, (cc) An HC containing the HC CDR of the HC of P1-068748, an LC containing the LC CDR 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, (dd) An HC containing the HC CDR of the HC of P1-068750, an LC containing the LC CDR 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, (ee) An HC containing the HC CDR of the HC of P1-068752, an LC containing the LC CDR 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, (ff) An HC containing the HC CDR of the HC of P1-068754, an LC containing the LC CDR 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, (gg) An HC containing the HC CDR of the HC of P1-068761_E55A.IgG1.3, an LC containing the LC CDR 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, (hh) An HC containing the HC CDR of the HC of P1-068761_H100G.IgG1.3, an LC containing the LC CDR 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, (ii) An HC containing the HC CDR of the HC of P1-068761_E56N.IgG1.3, an LC containing the LC CDR 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, (jj) An HC containing the HC CDR of the HC of P1-068761_E55A_E56N.IgG1.3, an LC containing the LC CDR of P1-08761_E55A_E56N, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068761_E55A_E56N.IgG1.3 respectively, (kk) An HC containing the HC CDR of the HC of P1-068761_E30D.IgG1.3, an LC containing the LC CDR 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, (ll) An HC containing the HC CDR of the HC of P1-068761_E30D._E55A.IgG1.3, an LC containing the LC CDR 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, (mm) An HC containing the HC CDR of the HC of P1-068761_E56N_H100G.IgG1.3, an LC containing the LC CDR 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, (nn) An HC containing the HC CDR of the HC of P1-068761_E30D_H100G.IgG1.3, an LC containing the LC CDR 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, (oo) An HC containing the HC CDR of the HC of P1-068761_E30D_E56N.IgG1.3, an LC containing the LC CDR 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, (pp) An HC containing the HC CDR of the HC of P1-068761_E100fF.IgG1.3, an LC containing the LC CDR of P1-068761_E100fF, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068761_E100fF.IgG1.3 respectively, (qq) An HC containing the HC CDR of the HC of P1-068761_E55A_E100fF.IgG1.3, an LC containing the LC CDR 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, (rr) An HC containing the HC CDR of the HC of P1-068761_H100G_E100fF.IgG1.3, an LC containing the LC CDR 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, (ss) An HC containing the HC CDR of the HC of P1-068761_E30D_E100fF.IgG1.3, an LC containing the LC CDR 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, (tt)An HC containing the HC CDR of the HC of P1-068761_E56N_E100fF.IgG1.3, an LC containing the LC CDR of P1-068761_E56N_E100fF, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068761_E56N_E100fF.IgG1.3 respectively, (uu)An HC containing the HC CDR of the HC of P1-068761_E32Y.IgG1.3, an LC containing the LC CDR 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, (vv)An HC containing the HC CDR of the HC of P1-068761_E32Y_E55A.IgG1.3, an LC containing the LC CDR 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, (ww)An HC containing the HC CDR of the HC of P1-068761_E32Y_E56N.IgG1.3, an LC containing the LC CDR of P1-068761_E32Y_E56N, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068761_E32Y_E56N.IgG1.3 respectively, (xx)An HC containing the HC CDR of the HC of P1-068761_E30D_E32Y.IgG1.3, an LC containing the LC CDR 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, (yy)An HC containing the HC CDR of the HC of P1-068761_E32Y_H100G.IgG1.3, an LC containing the LC CDR of P1-068761_E32Y_H100G, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068761_E32Y_H100G.IgG1.3, respectively, (zz)An HC containing the HC CDR of the HC of P1-068761_E32Y_E100fF.IgG1.3, an LC containing the LC CDR 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, (aaa)An HC containing the HC CDR of the HC of P1-068767_D52N_D102V.IgG1.3, an LC containing the LC CDR 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 P1-68767_D52N_D102V.IgG1.3, respectively, (bbb) An HC containing the HC CDR of the HC of P1-068767_D52N.IgG1.3, an LC containing the LC CDR of P1-068767_D52N, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068767_D52N.IgG1.3 respectively, (ccc) An HC containing the HC CDR of the HC of P1-068767_D52N_E55A.IgG1.3, an LC containing the LC CDR 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, (ddd) An HC containing the HC CDR of the HC of P1-068767_E55A_D102V.IgG1.3, an LC containing the LC CDR 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 P1-068767_E55A_D102V.IgG1.3 respectively, (eee) An HC containing the HC CDR of the HC of P1-068767_D102V.IgG1.3, an LC containing the LC CDR 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, (fff)HCs containing the HC CDRs of the HC of P1-068767_E55A.IgG1.3 and LCs containing 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, (ggg)HCs containing the HC CDRs of the HC of P1-068767_E30D_D52N.IgG1.3 and LCs containing the LC CDRs of P1-068767_E30D_D52N, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068767_E30D_D52N.IgG1.3 respectively, (hhh)HCs containing the HC CDRs of the HC of P1-068767_E30D_D102V.IgG1.3 and LCs containing 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, (iii)HCs containing the HC CDRs of the HC of P1-068767_E30D.IgG1.3 and LCs containing 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, (jjj)HCs containing the HC CDRs of the HC of P1-068767_E30D_E55A.IgG1.3 and LCs containing the LC CDRs of P1-068767_E30D_E55A, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068767_E30D_E55A.IgG1.3 respectively, (kkk)HCs containing the HC CDRs of the HC of P1-068767_E100fF_D102V.IgG1.3 and LCs containing the LC CDRs of P1-068767_E100fF_D102V, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068767_E100fF_D102V.IgG1.3 respectively, (lll)HCs containing the HC CDRs of the HC of P1-068767_E55A_E100fF.IgG1.3 and LCs containing 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, (mmm)An HC containing the HC CDR of the HC of P1-068767_D52N_E100fF.IgG1.3, an LC containing the LC CDR of P1-068767_D52N_E100fF, and HC and LC amino acid sequences that are at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to the HC and LC of P1-068767_D52N_E100fF.IgG1.3, respectively, (nnn)An HC containing the HC CDR of the HC of P1-068767_E100fF.IgG1.3, an LC containing the LC CDR 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, (ooo)An HC containing the HC CDR of the HC of P1-068767_E30D_E100fF.IgG1.3, an LC containing the LC CDR 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, (ppp)A heavy chain (HC) containing the HC CDR of the HC of VISTA.4 and a light chain (LC) containing the LC CDR of VISTA.4, 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 VISTA.4.IgG1.3, respectively, (qqq)A heavy chain (HC) containing the HC CDR of VISTA.4_VL_A64G's HC, a light chain (LC) containing the LC CDR of VISTA.4_VL_A64G, 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 VISTA.4_VL_A64G.IgG1.3 respectively, (rrr)A heavy chain (HC) containing the HC CDR of P1-070976's HC, a light chain (LC) containing the LC CDR of P1-070976, 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 P1-070976.IgG1.3 respectively, (sss)A heavy chain (HC) containing the HC CDR of P1-071799's HC, a light chain (LC) containing the LC CDR of P1-071799, 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 P1-071799.IgG1.3 respectively, (ttt)A heavy chain (HC) containing the HC CDR of P1-071801's HC, a light chain (LC) containing the LC CDR of P1-071801, 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 P1-071801.IgG1.3 respectively, (uuu)A heavy chain (HC) comprising the HC CDR of the HC of P1-065333 and a light chain (LC) comprising the LC CDR of P1-065333, 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 P1-065333.IgG1.3, respectively may be included.

[0099] In some embodiments, the anti-hVISTA Ab is (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, (b) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-061015.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-061015, (c) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068757.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068757, (d) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068759.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068759, (e) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761, (f) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068763.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068763, (g) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068765.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068765, (h) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767, (i) a heavy chain consisting of the amino acid sequence of the heavy chain of P1-068769.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068769, (j) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068771.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068771, (k) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068773.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068773, (l) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068775.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068775, (m) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069059.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069059, (n) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069061.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069061, (o) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069063.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069063, (p) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069065.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069065, (q) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069067.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069067, (r) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069069.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069069, (s) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069071.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069071, (t) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069073.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069073, (u) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069075.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069075, (v) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-069077.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-069077, The heavy chain consisting of the amino acid sequence of the heavy chain of (w)P1-068736 and the light chain consisting of the amino acid sequence of the light chain of P1-068736, (x) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068738.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068738, (y) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068740.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068740, (z) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068742.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068742, (aa) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068744.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068744, (bb) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068746.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068746, (cc) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068748.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068748, (dd) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068750.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068750, (ee) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068752.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068752, (ff) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068754 and the light chain consisting of the amino acid sequence of the light chain of P1-068754, (gg) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A, (hh) The heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_H100G.IgG1.3 and the light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G, (ii) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N, (jj) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A_E56N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E56N, (kk) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D, (ll) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E55A.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E55A, (mm) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N_H100G.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_H100G, (nn) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_H100G.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_H100G, (oo) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E56N.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E56N, (pp) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E100fF, (qq) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E55A_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E100fF, (rr) A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_H100G_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G_E100fF, (ss)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E100fF.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E100fF, (tt)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E56N_E100fF.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_E100fF, (uu)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y, (vv)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_E55A.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E55A, (ww)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_E56N.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E56N, (xx)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E30D_E32Y.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E32Y, (yy)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_H100G.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_H100G, (zz)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068761_E32Y_E100fF.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E100fF, (aaa)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N_D102V.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_D102V, (bbb)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N, (ccc)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N_E55A.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E55A, (ddd)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A_D102V.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A_D102V, (eee)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D102V.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_D102V, (fff)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A, (ggg)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_D52N.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D52N, (hhh)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_D102V.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D102V, (iii)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D, (jjj)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E30D_E55A.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_E55A, (kkk)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E100fF_D102V.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1-068767_E100fF_D102V, (lll)Heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E55A_E100fF.IgG1.3 and light chain consisting of the amino acid sequence of the light chain of P1068767_E55A_E100fF, (mmm)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_D52N_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E100fF, (nnn)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-068767_E100fF.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E100fF, (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, (ppp)A heavy chain consisting of the amino acid sequence of the heavy chain of VISTA.4.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of VISTA.4, (qqq)A heavy chain consisting of the amino acid sequence of the heavy chain of VISTA.4_VL_A64.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of VISTA.4_VL_A64, (rrr)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-070976.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-070976, (sss)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-071799.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-071799, (ttt)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-071801.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-071801, or (uuu)A heavy chain consisting of the amino acid sequence of the heavy chain of P1-065333.IgG1.3 and a light chain consisting of the amino acid sequence of the light chain of P1-065333 may be included.

[0100] In some embodiments, the present disclosure a heavy chain consisting of the amino acid sequence of the heavy chains (a) to (uuu) listed above followed by a Lys residue and a light chain consisting of the amino acid sequences of the light chains (a) to (uuu) listed above Comprising, and contemplating an anti-VISTA mA in which the heavy and light chain amino acid sequences are selected from the same antibody species among (a) to (uuu) listed above.

[0101] In some embodiments, the anti-hVISTA Ab may comprise a heavy chain amino acid sequence comprising the VH amino acid sequence of the antibody species herein rather than the IgG1.3 heavy chain constant region as provided in the HC sequence in the Sequence Listing herein (see SEQ ID NO: 163), and the antibody may comprise a different heavy chain constant region sequence, e.g., a human wild-type IgG1 constant region, e.g., human IgG1 allotype f (IgG1f) (SEQ ID NO: 182) or a modified human IgG1 constant region, e.g., IgG1.1f (SEQ ID NO: 183) or a modified human IgG1 constant region, e.g., IgG1.P238K (SEQ ID NO: 184). Accordingly, embodiments of the present disclosure are (a) (i) a heavy chain comprising the amino acid sequence of the VH of P1-061029 (SEQ ID NO: 67) and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-061029 (SEQ ID NO: 70), (b) (i) a heavy chain comprising the amino acid sequence of the VH of P1-061015 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-061015, (c) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068757 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068757, (d) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068759 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068759, (e) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761, (f) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068763 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068763, (g)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068765 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068765, (h)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068767, (i)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068769, (j)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068771, (k)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068773, (l)(i) A heavy chain comprising the amino acid sequence of the VH of P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068775, (m)(i) A heavy chain comprising the amino acid sequence of the VH of P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069059, (n)(i) A heavy chain comprising the amino acid sequence of the VH of P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069061, (o)(i) A heavy chain comprising the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069063, (p)(i) A heavy chain comprising the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069065, (q)(i) A heavy chain comprising the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069067, (r) (i) A heavy chain comprising the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069069, (s) (i) A heavy chain comprising the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069071, (t) (i) A heavy chain comprising the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069073, (u) (i) A heavy chain comprising the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069075, (v) (i) A heavy chain comprising the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-069077, (w) (i) A heavy chain comprising the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068736, (x) (i) A heavy chain comprising the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068738, (y) (i) A heavy chain comprising the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068740, (z) (i) A heavy chain comprising the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068742, (aa) (i) A heavy chain comprising the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068744, (bb) A heavy chain comprising the amino acid sequence of VH of P1-068746 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068746, (cc) A heavy chain comprising the amino acid sequence of VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068748, (dd) A heavy chain comprising the amino acid sequence of VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068750, (ee) A heavy chain comprising the amino acid sequence of VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068752, (ff) A heavy chain comprising the amino acid sequence of VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068754, (gg) A heavy chain comprising the amino acid sequence of VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A, (hh) A heavy chain comprising the amino acid sequence of VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G, (ii) A heavy chain comprising the amino acid sequence of VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E56N, (jj) A heavy chain comprising the amino acid sequence of VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E56N, (kk) A heavy chain comprising the amino acid sequence of VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E30D, (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E55A (mm) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_H100G (nn) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_H100G (oo) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E56N (pp) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E100fF (qq) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E100fF (rr) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_H100G_E100fF (ss) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E100fF (tt) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E56N_E100fF, (uu) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y, (vv) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E55A, (ww) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E56N, (xx) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E32Y, (yy) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_H100G, (zz) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E32Y_E100fF, (aaa) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_D102V, (bbb) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_D52N, (ccc) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_D52N_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E55A, (ddd) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_D102V, (eee) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_D102V, (fff) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E55A, (ggg) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D52N and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D52N, (hhh) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_D102V, (iii) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E30D, (jjj) (i) The heavy chain comprising the amino acid sequence of the VH of P1-068767_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E55A, (kkk) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF_D102V, (lll) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E55A_E100fF, (mmm) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_D52N_E100fF, (nnn) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E100fF, (ooo) (i) The heavy chain comprising the amino acid sequence of VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-068767_E30D_E100fF, (ppp) (i) The heavy chain comprising the amino acid sequence of VH of VISTA.4 and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of VISTA.4, (qqq) (i) The heavy chain comprising the amino acid sequence of VH of VISTA.4_VL_A64 and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of VISTA.4_VL_A64, (rrr) (i) The heavy chain comprising the amino acid sequence of VH of P1-070976 and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-070976, (sss) (i) The heavy chain comprising the amino acid sequence of VH of P1-071799 and (ii) the amino acid sequence of SEQ ID NO: 182, and the light chain comprising the amino acid sequence of the light chain of P1-071799, (ttt)A heavy chain comprising the amino acid sequence of VH of P1-071801 (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain comprising the amino acid sequence of the light chain of P1-071801, or (uuu)A heavy chain comprising the amino acid sequence of VH of P1-065333 (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain comprising the amino acid sequence of the light chain of P1-065333 comprising an anti-VISTA Ab.

[0102] Certain embodiments of the present disclosure (a) A heavy chain consisting of (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 consisting of the amino acid sequence of the light chain of P1-061029 (SEQ ID NO: 70), (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 amino acid sequence of the light chain of P1-061015, (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 amino acid sequence of the light chain of P1-068757, (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 amino acid sequence of the light chain of P1-068759, (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 amino acid sequence of the light chain of P1-068761, (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 amino acid sequence of the light chain of P1-068763, (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 amino acid sequence of the light chain of P1-068765, (i) a heavy chain consisting of the amino acid sequence of VH of (h(i)P1-068767 and (ii) the amino acid sequence of SEQ ID NO: 182), and a light chain consisting of the amino acid sequence of the light chain of P1-068767, (i) a heavy chain consisting of the amino acid sequence of VH of (i)P1-068769 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068769, (j) a heavy chain consisting of the amino acid sequence of VH of (i)P1-068771 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068771, (k) a heavy chain consisting of the amino acid sequence of VH of (i)P1-068773 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068773, (l) a heavy chain consisting of the amino acid sequence of VH of (i)P1-068775 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068775, (m) a heavy chain consisting of the amino acid sequence of VH of (i)P1-069059 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069059, (n) a heavy chain consisting of the amino acid sequence of VH of (i)P1-069061 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069061, (o) a heavy chain consisting of the amino acid sequence of VH of (i)P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069063, (p) a heavy chain consisting of the amino acid sequence of VH of (i)P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069065, (q) a heavy chain consisting of the amino acid sequence of VH of (i)P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069067, (r) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069069, (s) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069071, (t) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069073, (u) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069075, (v) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-069077, (w) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068736, (x) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068738, (y) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068740, (z) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068742, (aa) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068744, (bb) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068746 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068746, (cc) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068748, (dd) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068750, (ee) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068752, (ff) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068754, (gg) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A, (hh) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G, (ii) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N, (jj) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E56N, (kk) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D, (ll) (i) A heavy chain consisting of 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 amino acid sequence of the light chain of P1-068761_E30D_E55A (mm) (i) A heavy chain consisting of 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 amino acid sequence of the light chain of P1-068761_E56N_H100G (nn) (i) A heavy chain consisting of 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 amino acid sequence of the light chain of P1-068761_E30D_H100G (oo) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E56N (pp) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E100fF (qq) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E55A_E100fF (rr) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_H100G_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_H100G_E100fF (ss) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E100fF (tt) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E56N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E56N_E100fF (uu) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y (vv) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_E55A and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E55A (ww) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_E56N and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E56N (xx) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E30D_E32Y and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E30D_E32Y (yy) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_H100G and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_H100G (zz) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068761_E32Y_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068761_E32Y_E100fF (aaa) (i) A heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_D102V (bbb) A heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N, (ccc) A heavy chain consisting of the amino acid sequence of VH of P1-068767_D52N_E55A (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D52N_E55A, (ddd) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A_D102V (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A_D102V, (eee) A heavy chain consisting of the amino acid sequence of VH of P1-068767_D102V (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_D102V, (fff) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E55A (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E55A, (ggg) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_D52N (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D52N, (hhh) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_D102V (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_D102V, (iii) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D, (jjj) A heavy chain consisting of the amino acid sequence of VH of P1-068767_E30D_E55A (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-068767_E30D_E55A, (kkk) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068767_E100fF_D102V and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-068767_E100fF_D102V (lll) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068767_E55A_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-068767_E55A_E100fF (mmm) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068767_D52N_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-068767_D52N_E100fF (nnn) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068767_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-068767_E100fF (ooo) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-068767_E30D_E100fF and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-068767_E30D_E100fF (ppp) A heavy chain consisting of (i) the amino acid sequence of the VH of VISTA.4 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of VISTA.4 (qqq) A heavy chain consisting of (i) the amino acid sequence of the VH of VISTA.4_VL_A64 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of VISTA.4_VL_A64 (rrr) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-070976 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-070976 (sss) A heavy chain consisting of (i) the amino acid sequence of the VH of P1-071799 and (ii) the amino acid sequence of SEQ ID NO: 182, and a light chain consisting of the amino acid sequence of the VL of P1-071799 (ttt)A heavy chain consisting of the amino acid sequence of VH of P1-071801 (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-071801, or (uuu)A heavy chain consisting of the amino acid sequence of VH of P1-065333 (i) and the amino acid sequence of SEQ ID NO: 182 (ii), and a light chain consisting of the amino acid sequence of the light chain of P1-065333 An anti-VISTA Ab comprising a C-terminal amino acid of VH and an N-terminal amino acid of SEQ ID NO: 182 form a peptide bond.

[0103] In some embodiments, the present disclosure Comprising (i) VH of (a)-(uuu) listed above, (ii) SEQ ID NO: 182, and (iii) the amino acid sequence of 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 connected to the N-terminus of Lys, a heavy chain, and A light chain consisting of the amino acid sequence of the light chain of (a)-(uuu) listed above Including An anti-VISTA mAb is contemplated in which the VH and light chain amino acid sequences are selected from the same antibody species among (a)-(uuu) listed above.

[0104] Certain embodiments of the present disclosure (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 amino acid sequence of the light chain of P1-061029 (SEQ ID NO: 70), (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 amino acid sequence of the light chain of P1-061015, (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 amino acid sequence of the light chain of P1-068757, (d) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068759, (e) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068761, (f) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068763, (g) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068765, (h) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068767, (i) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068769, (j) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068771, (k) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068773, (l) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-068775, (m) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-069059, (n) (i) A heavy chain comprising 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 amino acid sequence of the light chain of P1-069061, (o) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069063 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069063, (p) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069065 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069065, (q) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069067 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069067, (r) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069069 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069069, (s) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069071 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069071, (t) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069073 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069073, (u) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069075 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069075, (v) A heavy chain comprising (i) the amino acid sequence of the VH of P1-069077 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-069077, (w) A heavy chain comprising (i) the amino acid sequence of the VH of P1-068736 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068736, (x) A heavy chain comprising (i) the amino acid sequence of the VH of P1-068738 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068738, (y) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068740 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068740, (z) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068742 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068742, (aa) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068744 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068744, (bb) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068746 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068746, (cc) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068748 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068748, (dd) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068750 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068750, (ee) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068752 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068752, (ff) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068754 and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068754, (gg) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068761_E55A, (hh) (i) a heavy chain comprising the amino acid sequence of the VH of P1-068761_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and a light chain comprising the amino acid sequence of the light chain of P1-068761_H100G, (ii) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E56N (jj) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E55A_E56N and (ii) the amino acid sequence of SEQ ID NO: 183, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E55A_E56N (kk) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D and (ii) the amino acid sequence of SEQ ID NO: 183, and the light chain comprising the amino acid sequence of the light chain of 068761_E30D (ll) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E30D_E55A and (ii) the amino acid sequence of SEQ ID NO: 183, and the light chain comprising the amino acid sequence of the light chain of P1-068761_E30D_E55A (mm) (i) The heavy chain comprising the amino acid sequence of VH of P1-068761_E56N_H100G and (ii) the amino acid sequence of SEQ ID NO: 183, and the light chain...

Claims

**Claim 1** An antibody that specifically binds to hVISTA under acidic conditions, wherein the antibody comprises heavy and light chains each containing the VH and VL CDRs of P1-070976 (SEQ ID NOs: 509-511 and 500-502 respectively), P1-070976_H95D (SEQ ID NOs: 512-514 and 500-502 respectively), VISTA.4 (SEQ ID NOs: 503-505 and 500-502 respectively), P1-065333 (SEQ ID NOs: 506-508 and 500-502 respectively) or P1-070976_E97P (SEQ ID NOs: 515-517 and 500-502 respectively), and the acidic conditions are conditions having a pH of 6.0-6.

5. **Claim 2** The antibody according to claim 1, comprising a heavy chain variable region (VH) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH of VISTA.4 (SEQ ID NO: 492), P1-070976 (SEQ ID NO: 474), P1-065333 (SEQ ID NO: 473), P1-070976_H95D (SEQ ID NO: 477) or P1-070976_E97P (SEQ ID NO: 478). **Claim 3** The antibody according to claim 1 or 2, comprising a light chain variable region (VL) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VL of VISTA.4, P1-070976, P1-065333, P1-070976_H95D or P1-070976_E97P (corresponding to SEQ ID NO: 493 or SEQ ID NO: 479). **Claim 4** The antibody according to any one of claims 1 to 3, comprising VH and VL that are at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH and VL of VISTA.4 (SEQ ID NOs: 492 and 479 or SEQ ID NOs: 492 and 493), P1-070976 (SEQ ID NOs: 474 and 479 or SEQ ID NOs: 474 and 493), P1-065333 (SEQ ID NOs: 473 and 479 or SEQ ID NOs: 473 and 493), P1-070976_H95D (SEQ ID NOs: 477 and 479 or SEQ ID NOs: 477 and 493), or P1-070976_E97P (SEQ ID NOs: 478 and 479 or SEQ ID NOs: 478 and 493). **Claim 5** The antibody according to any one of claims 1 to 4, comprising a VH of P1-070976 (SEQ ID NO: 474), P1-070976_H95D (SEQ ID NO: 477), VISTA.4 (SEQ ID NO: 492), P1-065333 (SEQ ID NO: 473) or P1-070976_E97P (SEQ ID NO: 478).

6. The antibody according to any one of claims 1 to 4, comprising a VL of P1-070976, P1-070976_H95D, VISTA.4, P1-065333 or P1-070976_E97P (with or without A64G) (corresponding to SEQ ID NO: 493 (without A64G) or SEQ ID NO: 479 (with A64G)).

7. The antibody according to any one of claims 1 to 6, comprising a VH and a VL of P1-070976 (SEQ ID NO: 474 and 479 or SEQ ID NO: 474 and 493), P1-070976_H95D (SEQ ID NO: 477 and 479 or SEQ ID NO: 477 and 493), VISTA.4 (SEQ ID NO: 492 and 479 or SEQ ID NO: 492 and 493), P1-065333 (SEQ ID NO: 473 and 479 or SEQ ID NO: 473 and 493) or P1-070976_E97P (SEQ ID NO: 478 and 479 or SEQ ID NO: 478 and 493).

8. The antibody according to any one of claims 1 to 7, comprising a heavy chain (HC) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the HC of VISTA.4.IgG1.3 (SEQ ID NO: 491), P1-070976.IgG1.3 (SEQ ID NO: 476), P1-065333.IgG1.3 (SEQ ID NO: 475), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480) or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481).

9. An antibody according to any one of claims 1 to 7, comprising a light chain (LC) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the LC of VISTA.4.IgG1.3, P1-070976.IgG1.3, P1-065333.IgG1.3, P1-070976_H95D.IgG1.3 or P1-070976_E97P.IgG1.3, which has or does not have an A64G substitution in VL (SEQ ID NO: 494 (without A64G) or SEQ ID NO: 482 (with A64G)).

10. An antibody according to any one of claims 1 to 9, comprising an HC and an LC that are at least 90%, at least 95%, at least 97%, or at least 99% identical to the HC and LC of VISTA.4.IgG1.3 (SEQ ID NO: 491 and 494 or SEQ ID NO: 491 and 482), P1-070976.IgG1.3 (SEQ ID NO: 476 and 494 or SEQ ID NO: 476 and 482), P1-065333.IgG1.3 (SEQ ID NO: 475 and 494 or SEQ ID NO: 475 and 482), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480 and 494 or SEQ ID NO: 480 and 482) or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481 and 494 or SEQ ID NO: 481 and 482), which has or does not have an A64G in VL.

11. An antibody according to any one of claims 1 to 10, comprising the HC of P1-070976.IgG1.3 (SEQ ID NO: 476), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480), VISTA.4.IgG1.3 (SEQ ID NO: 491), P1-065333.IgG1.3 (SEQ ID NO: 475) or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481).

12. An antibody according to any one of claims 1 to 10, comprising the LC of P1-070976.IgG1.3, P1-070976_H95D.IgG1.3, VISTA.4.IgG1.3, P1-065333.IgG1.3 or P1-070976_E97P.IgG1.3, which has or does not have an A64G in VL, SEQ ID NO: 494 (without A64G) or SEQ ID NO: 482 (with A64G).

13. The antibody according to any one of claims 1 to 12, comprising HC and LC (with or without A64G in VL) of P1-070976.IgG1.3 (SEQ ID NOs: 476 and 494 or SEQ ID NOs: 476 and 482), P1-070976_H95D.IgG1.3 (SEQ ID NOs: 480 and 494 or SEQ ID NOs: 480 and 482), VISTA.4.IgG1.3 (SEQ ID NOs: 491 and 494 or SEQ ID NOs: 491 and 482), P1-065333.IgG1.3 (SEQ ID NOs: 475 and 494 or SEQ ID NOs: 475 and 482), or P1-070976_E97P.IgG1.3 (SEQ ID NOs: 481 and 494 or SEQ ID NOs: 481 and 482).

14. The antibody is - an antibody comprising a full-length antibody or a full-length heavy chain (with or without a C-terminal lysine) and a full-length light chain; - an antigen-binding fragment; - a multimeric or dimeric antibody; or - linked to another molecule that is a labeled, peptide, antibody-drug conjugate (ADC) or activatable antibody, The antibody according to any one of claims 1 to 13.

15. An antibody that specifically binds to hVISTA and inhibits VISTA-mediated T cell activation, wherein the antibody comprises a heavy chain and a light chain each containing the VH and VL CDRs of P1-070976 (SEQ ID NOs: 509-511 and 500-502 respectively), P1-070976_H95D (SEQ ID NOs: 512-514 and 500-502 respectively), VISTA.4 (SEQ ID NOs: 503-505 and 500-502 respectively), P1-065333 (SEQ ID NOs: 506-508 and 500-502 respectively) or P1-070976_E97P (SEQ ID NOs: 515-517 and 500-502 respectively).

16. The antibody according to claim 15, comprising a heavy chain variable region (VH) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH of VISTA.4 (SEQ ID NO: 492), P1-070976 (SEQ ID NO: 474), P1-065333 (SEQ ID NO: 473), P1-070976_H95D (SEQ ID NO: 477) or P1-070976_E97P (SEQ ID NO: 478).

17. The antibody according to claim 15 or 16, comprising a light chain variable region (VL) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the VL of VISTA.4, P1-070976, P1-065333, P1-070976_H95D or P1-070976_E97P (corresponding to SEQ ID NO: 493 or SEQ ID NO: 479).

18. The antibody according to any one of claims 15 to 17, comprising VH and VL that are at least 90%, at least 95%, at least 97%, or at least 99% identical to the VH and VL of VISTA.4 (SEQ ID NOs: 492 and 479 or SEQ ID NOs: 492 and 493), P1-070976 (SEQ ID NOs: 474 and 479 or SEQ ID NOs: 474 and 493), P1-065333 (SEQ ID NOs: 473 and 479 or SEQ ID NOs: 473 and 493), P1-070976_H95D (SEQ ID NOs: 477 and 479 or SEQ ID NOs: 477 and 493), or P1-070976_E97P (SEQ ID NOs: 478 and 479 or SEQ ID NOs: 478 and 493).

19. The antibody according to any one of claims 15 to 18, comprising the VH of P1-070976 (SEQ ID NO: 474), P1-070976_H95D (SEQ ID NO: 477), VISTA.4 (SEQ ID NO: 492), P1-065333 (SEQ ID NO: 473) or P1-070976_E97P (SEQ ID NO: 478).

20. The antibody according to any one of claims 15 to 18, comprising the VL of P1-070976, P1-070976_H95D, VISTA.4, P1-065333 or P1-070976_E97P (with or without A64G) (corresponding to SEQ ID NO: 493 (without A64G) or SEQ ID NO: 479 (with A64G)).

21. The antibody according to any one of claims 15 to 20, comprising VH and VL of P1-070976 (SEQ ID NO: 474 and 479 or SEQ ID NO: 474 and 493), P1-070976_H95D (SEQ ID NO: 477 and 479 or SEQ ID NO: 477 and 493), VISTA.4 (SEQ ID NO: 492 and 479 or SEQ ID NO: 492 and 493), P1-065333 (SEQ ID NO: 473 and 479 or SEQ ID NO: 473 and 493) or P1-070976_E97P (SEQ ID NO: 478 and 479 or SEQ ID NO: 478 and 493).

22. The antibody according to any one of claims 15 to 21, comprising a heavy chain (HC) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the HC of VISTA.4.IgG1.3 (SEQ ID NO: 491), P1-070976.IgG1.3 (SEQ ID NO: 476), P1-065333.IgG1.3 (SEQ ID NO: 475), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480) or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481).

23. The antibody according to any one of claims 15 to 21, comprising a light chain (LC) that is at least 90%, at least 95%, at least 97%, or at least 99% identical to the LC of VISTA.4.IgG1.3, P1-070976.IgG1.3, P1-065333.IgG1.3, P1-070976_H95D.IgG1.3 or P1-070976_E97P.IgG1.3, having or not having an A64G substitution in the VL (SEQ ID NO: 494 (without A64G) or SEQ ID NO: 482 (with A64G)).

24. The antibody according to any one of claims 15 to 23, comprising HC and LC that are at least 90%, at least 95%, at least 97%, or at least 99% identical to the HC and LC of VISTA.4.IgG1.3 (SEQ ID NOs: 491 and 494 or SEQ ID NOs: 491 and 482), P1-070976.IgG1.3 (SEQ ID NOs: 476 and 494 or SEQ ID NOs: 476 and 482), P1-065333.IgG1.3 (SEQ ID NOs: 475 and 494 or SEQ ID NOs: 475 and 482), P1-070976_H95D.IgG1.3 (SEQ ID NOs: 480 and 494 or SEQ ID NOs: 480 and 482) or P1-070976_E97P.IgG1.3 (SEQ ID NOs: 481 and 494 or SEQ ID NOs: 481 and 482) (with or without A64G in VL).

25. The antibody according to any one of claims 15 to 24, comprising the HC of P1-070976.IgG1.3 (SEQ ID NO: 476), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480), VISTA.4.IgG1.3 (SEQ ID NO: 491), P1-065333.IgG1.3 (SEQ ID NO: 475) or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481).

26. The antibody according to any one of claims 15 to 24, comprising the LC of P1-070976.IgG1.3, P1-070976_H95D.IgG1.3, VISTA.4.IgG1.3, P1-065333.IgG1.3 or P1-070976_E97P.IgG1.3 (with or without A64G in VL), SEQ ID NO: 494 (without A64G) or SEQ ID NO: 482 (with A64G).

27. The antibody according to any one of claims 15 to 26, comprising the HC and LC (with or without A64G in VL) of P1-070976.IgG1.3 (SEQ ID NO: 476 and 494 or SEQ ID NO: 476 and 482), P1-070976_H95D.IgG1.3 (SEQ ID NO: 480 and 494 or SEQ ID NO: 480 and 482), VISTA.4.IgG1.3 (SEQ ID NO: 491 and 494 or SEQ ID NO: 491 and 482), P1-065333.IgG1.3 (SEQ ID NO: 475 and 494 or SEQ ID NO: 475 and 482), or P1-070976_E97P.IgG1.3 (SEQ ID NO: 481 and 494 or SEQ ID NO: 481 and 482).

28. The antibody is a. an antibody comprising a full-length antibody or a full-length heavy chain (with or without a C-terminal lysine) and a full-length light chain; b. an antigen-binding fragment; c. a multimeric or dimeric antibody; or d. linked to another molecule that is a labeled, peptide, antibody-drug conjugate (ADC) or activatable antibody, the antibody according to any one of claims 15 to 27.

29. The antibody according to any one of claims 1 to 7 or 15 to 21, comprising a wild-type human IgG1 (SEQ ID NO: 182), wild-type human IgG2, wild-type human IgG3, wild-type human IgG4, wild-type human IgG4 containing the S228P substitution, IgG1.1 (SEQ ID NO: 183), IgG1.3 (SEQ ID NO: 163), or a heavy chain constant region containing IgG1.P238K (SEQ ID NO: 184), with or without a C-terminal lysine.

30. The antibody according to any one of claims 1 to 7 or 15 to 21, comprising a heavy chain (HC) containing SEQ ID NO: 475, 476, 491, 480 or 481, with or without a signal peptide.

31. The antibody according to any one of claims 1 to 7 or 15 to 30, comprising a light chain containing SEQ ID NO: 472, 494 or 482, with or without a signal peptide.

32. a) SEQ ID NO: 475 and SEQ ID NO: 482 or 472, respectively, b) SEQ ID NO: 475 and SEQ ID NO: 494, respectively, c) SEQ ID NO: 476 and SEQ ID NO: 482 or 472, respectively, d) SEQ ID NO: 476 and SEQ ID NO: 494, respectively, (e) each, SEQ ID NO: 491 and SEQ ID NO: 482 or 472, (f) each, SEQ ID NO: 491 and SEQ ID NO: 494, (g) each, SEQ ID NO: 480 and SEQ ID NO: 482 or 472, (h) each, SEQ ID NO: 480 and SEQ ID NO: 494, (i) each, SEQ ID NO: 481 and SEQ ID NO: 482 or 472, or (j) each, SEQ ID NO: 481 and SEQ ID NO: 494 The antibody according to claim 31, comprising a heavy chain and a light chain each containing the above.

33. The antibody has one or more of the following characteristics: a. Specifically binds to hVISTA under acidic conditions but does not significantly bind under neutral or physiological conditions, where the acidic condition is a condition having a pH of 6.0 to 6.5 and the physiological condition is a condition having a pH of 7.4; b. Under acidic conditions, its K in neutral or physiological conditions Ｄ is at least 10-fold lower than K Ｄ for binding to hVISTA, where the neutral condition is the condition having a pH of 7.0 and the physiological condition is the condition having a pH of 7.4; c. Under acidic conditions, its k under neutral or physiological conditions ｏｆｆ is at least 5-fold, at least 10-fold, at least 50-fold, or at least 100-fold lower than k ｏｆｆ for binding to hVISTA, where the acidic condition is a condition having a pH of 6.0 to 6.5, the neutral condition is a condition having a pH of 7.0, and the physiological condition is a condition having a pH of 7.4; d. Inhibits the binding of hVISTA to human T cells under conditions having a pH of less than 7.0; e. Inhibits the binding of hVISTA to huPSGL-1 and / or competes with huPSGL1 for the binding to hVISTA under conditions having a pH of less than 7.0; f. Inhibits the binding of hVISTA to heparan sulfate proteoglycan; g. Inhibits the binding of hVISTA to heparan sulfate proteoglycan under conditions having a pH of less than 7.0; h. Stimulates T cell activation as demonstrated by enhancing T cell proliferation, enhancing IFN-γ production from T cells, and / or stimulating T cell receptor-mediated NF-κB signaling under conditions having a pH of less than 7.0; i. Reduces VISTA-mediated cell-cell adhesion; j. Has an average residence time (MRT) of at least 100, 200, 300, 400, or 500 days in cynomolgus monkeys; k. Does not significantly bind to VISTA-positive cells in the peripheral blood of the administered subject; l. Does not significantly deplete VISTA-positive cells in the peripheral blood of the administered subject; m. Binds in or near the histidine-rich region of hVISTA; and n. Binds in or near the histidine-rich region of hVISTA under conditions having a pH of 6.0 to 6.

5. The antibody according to any one of claims 1 to 32 having the above characteristics.

34. A nucleic acid encoding the antibody according to any one of claims 1 to 33.

35. A nucleic acid encoding the heavy and light chains of the antibody according to any one of claims 1 to 33 or a set of at least two nucleic acids.

36. A composition comprising a nucleic acid encoding the heavy chain of the antibody according to any one of claims 1 to 33 and a nucleic acid encoding the light chain of the antibody.

37. A cell comprising the nucleic acid according to any one of claims 34 or 35 or the composition according to claim 36.

38. A method for preparing an antibody, comprising culturing the cell according to claim 37 under conditions under which the antibody is expressed, wherein the cell comprises a set of nucleic acids encoding both the heavy and light chains of the antibody.

39. A composition comprising the antibody, nucleic acid, composition or cell according to any one of claims 1 to 37 and a pharmaceutically acceptable carrier.

40. An antibody according to any one of claims 1 to 33 or a composition according to claim 36 for treating cancer in a subject, wherein the antibody or composition is an immune response-stimulating and / or VISTA antagonist antibody.

41. The antibody or composition according to claim 40, wherein the subject has VISTA-positive cells.

42. The antibody or composition according to claim 40 or 41, wherein the subject is first tested for the presence of VISTA-positive cells in the tumor, and if the subject has VISTA-positive cells, the subject is treated.

43. The antibody or composition according to claim 40 or 41, wherein the subject is further administered a second therapy, the second therapy comprising chemotherapy, radiation therapy, surgery or administration of a second agent, and when the second therapy comprises administration of a second agent, the second agent is an immune activator.

44. A composition according to claim 36 or an antibody according to any one of claims 1 to 33 for treating cancer in a subject, wherein the treatment further comprises administering a PD1 / PD-L1 pathway antagonist that results in an increase in the number of CD4+ and CD8+ T cells in the subject's tumor and / or a reduction in the number of exhausted T cells and / or T cells expressing PD-1, LAG3 and / or TIM-3 in the subject's tumor.

45. A composition according to claim 36 or an antibody according to any one of claims 1 to 33 for treating an infectious disease in a subject, wherein the antibody or composition is an immunostimulant and / or a VISTA antagonist, the composition or antibody.

46. A method for detecting VISTA in a sample in vitro, the method comprising contacting the sample with an antibody according to any one of claims 1 to 33.

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