Vista antigen-binding molecules

Abstract

The present disclosure relates to anti-VISTA antigen-binding molecules, as well as nucleic acids and expression vectors encoding, and compositions comprising the anti-VISTA antigen-binding molecules. Methods of using said molecules and articles for treating or preventing disease are also disclosed.

Description

VISTA Antigen-Binding MoleculesThis application claims priority from US 63 / 696089, filed 18 September 2024, the contents and elements of which are herein incorporated by reference for all purposes.Technical FieldThe present disclosure relates to molecular biology, more specifically antibody technology. The present disclosure also relates to methods of medical treatment and prophylaxis.BackgroundV-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is an immune checkpoint molecule, which is highly expressed on Myeloid Derived Suppressor Cells (MDSCs), in particular tumor-infiltrating MDSCs, and also on tumor-infiltrating myeloid DCs (Le Mercier et al., Cancer Res. (2014) 74(7):1933-44), tumor-associated macrophages (TAMs) and neutrophils. MDSC-mediated suppression of immune response has been identified in multiple solid tumors and lymphomas. MDSCs are elevated in advanced colorectal cancer (Toor et al, Front Immunol. 2016; 7:560). MDSCs are also observed in breast cancer, and the percentage of MDSCs in the peripheral blood is increased in patients with later stage breast cancer (Markowitz et al, Breast Cancer Res Treat. 2013 Jul; 140(1 ):13-21 ). MDSC abundance is also correlated with poor prognosis in solid tumors (Charoentong et al, Cell Rep. 2017 Jan 3; 18(1):248-262).Targeting VISTA is an attractive therapeutic strategy for removing MDSC-mediated suppression of effector immune cell function.SummaryThe present invention relates to anti-VISTA antigen-binding molecules, articles comprising or encoding said antigen-binding molecules, and the use of such molecules / articles for treating or preventing disease e.g. cancer.In one aspect, the present invention provides an antigen-binding molecule, optionally isolated, comprising:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NO:42 or 70 HC-CDR3 having the amino acid sequence of SEQ ID NO:43 or 76; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs: HC-CDR1 having the amino acid sequence of SEQ ID NO:41HC-CDR2 having the amino acid sequence of SEQ ID NO:42 HC-CDR3 having the amino acid sequence of SEQ ID NO:43; and / or(ii) a light chain variable (VL) region incorporating the following CDRs: LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:76; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:71 ; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:72; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs: HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:73; and / or(ii) a light chain variable (VL) region incorporating the following CDRs: LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NO:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .In some embodiments, the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs): HC-FR1 having the amino acid sequence of SEQ ID NO:57 HC-FR2 having the amino acid sequence of SEQ ID NO:58 HC-FR3 having the amino acid sequence of SEQ ID NO:77 HC-FR4 having the amino acid sequence of SEQ ID NQ:60.In some embodiments, the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs): HC-FR1 having the amino acid sequence of SEQ ID NO:57 HC-FR2 having the amino acid sequence of SEQ ID NO:58 HC-FR3 having the amino acid sequence of SEQ ID NO:59 HC-FR4 having the amino acid sequence of SEQ ID NQ:60.In some embodiments, the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs): HC-FR1 having the amino acid sequence of SEQ ID NO:57 HC-FR2 having the amino acid sequence of SEQ ID NO:58 HC-FR3 having the amino acid sequence of SEQ ID NO:74 HC-FR4 having the amino acid sequence of SEQ ID NQ:60.In some embodiments, the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs): HC-FR1 having the amino acid sequence of SEQ ID NO:57 HC-FR2 having the amino acid sequence of SEQ ID NO:58 HC-FR3 having the amino acid sequence of SEQ ID NO:75 HC-FR4 having the amino acid sequence of SEQ ID NQ:60.In some embodiments, the antigen-binding molecule comprises: a VL region incorporating the following framework regions (FRs): LC-FR1 having the amino acid sequence of SEQ ID NO:62 LC-FR2 having the amino acid sequence of SEQ ID NO:63 LC-FR3 having the amino acid sequence of SEQ ID NO:64 LC-FR4 having the amino acid sequence of SEQ ID NO:65.In some embodiments, the antigen-binding molecule comprises:a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:56, 66, 67, 68, or 69; and / or a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some aspects, an antigen-binding molecule of the invention comprises: a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:99; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NQ:101 .In some embodiments, any of the antigen-binding molecules of the invention comprises a heavy chain comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78 and comprises the substitutions L234A, L235A and P329A (residues A117, A118 and A212 in SEQ ID NO:78).In some embodiments, any of the antigen-binding molecules of the invention comprises:(a) (i) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84, 87, 90, 93, or 96; and / or(ii) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:98; or(b) (i) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NQ:100; and / or(ii) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:102.Also provided is an antibody-drug conjugate comprising an antigen-binding molecule provided herein.Also provided is a nucleic acid, or a plurality of nucleic acids, optionally isolated, encoding an antigenbinding molecule provided herein. Also provided is an expression vector, or a plurality of expression vectors, comprising a nucleic acid or a plurality of nucleic acids described herein.Also provided is a composition comprising an antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector or a plurality of expression vectors described herein. In some embodiments, the composition comprises a pharmaceutically acceptable carrier, diluent, excipient or adjuvant.Also provided is a cell comprising an antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors or a composition described herein.Also provided is an antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors, composition or cell of the invention for use in a method of medical treatment or prophylaxis, or in a method of diagnosis or prognosis.Also provided is an antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors, composition or cell of the invention for use in treating or preventing a cancer.Also provided is the use of an antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors, composition or cell of the invention in the manufacture of a medicament for treating or preventing a cancer.Also provided is a method of treating or preventing a cancer, comprising administering to a subject a therapeutically- or prophylactically-effective amount of an antigen-binding molecule antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors, composition or cell of the invention.In some embodiments, the cancer is selected from: a cancer comprising cells expressing / overexpressing VISTA, a cancer comprising infiltration of cells expressing VISTA, a cancer characterised by the presence of cells expressing VISTA in the vicinity of / proximal to cells of the cancer, a cancer comprising a tumor displaying infiltration of cells expressing VISTA, a hematological cancer, a myeloid hematologic cancer, leukemia, T cell leukemia, B cell leukemia, acute myeloid leukemia, chronic myelomonocytic leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, lymphoma, B cell lymphoma, T cell lymphoma, multiple myeloma, mesothelioma, epithelioid mesothelioma, myelodysplastic syndrome, gliblastoma multiforme, brain lower grade glioma, sarcoma, testicular germ cell tumor, myeloproliferative disorder, a solid tumor, lung cancer, non-small cell lung cancer, gastric cancer, gastric carcinoma, colorectal cancer, colorectal carcinoma, colorectal adenocarcinoma, uterine cancer, uterine corpus endometrial carcinoma, breast cancer, triple negative breast cancer, triple negative breast invasive carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, thyroid cancer, thymoma, skin cancer, melanoma, cutaneous melanoma, kidney cancer, renal cell carcinoma, renal papillary cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, ovarian cancer, ovarian carcinoma, ovarian serous cystadenocarcinoma, prostate cancer and prostate adenocarcinoma.Also provided is an in vitro complex, optionally isolated, comprising an antigen-binding molecule or an antibody-drug conjugate of the invention, bound to VISTA.Also provided is a method comprising contacting a sample containing, or suspected to contain, VISTA with an antigen-binding molecule or antibody-drug conjugate according to the invention, and detecting the formation of a complex of the antigen-binding molecule or ADC with VISTA.Also provided is a method of selecting or stratifying a subject for treatment with a VISTA-targeted agent, the method comprising contacting, in vitro, a sample from the subject with an antigen-binding molecule of the invention and detecting the formation of a complex of the antigen-binding molecule with VISTA.Also provided is the use of an antigen-binding molecule of the invention as an in vitro or in vivo diagnostic or prognostic agent.DescriptionThe present invention relates to novel VISTA-binding molecules having novel and / or improved properties as compared to known anti-VISTA antibodies.The inventors generated antigen-binding molecules which bind to particular regions of interest in the extracellular region of VISTA. The VISTA-binding molecules of the present invention are provided with combinations of desirable biophysical and functional properties as compared to VISTA-binding antigenbinding molecules disclosed in the prior art.VISTAVISTA (V-type immunoglobulin domain-containing suppressor of T-cell activation; also known e.g. as B7- H5, SISP1 , PD-1 H) is the protein identified by L)niProtKB:Q9H7M9. The canonical isoform of human VISTA has the amino acid sequence of Q9H7M9-1 (v3, 2010-11-02; SEQ ID NO:1 ). Human VISTA comprises a 32 amino acid N-terminal signal peptide (SEQ ID NO:2), followed by an extracellular domain (SEQ ID NO:3) comprising an Ig-like V-type domain (SEQ ID NO:4), a single-pass transmembrane domain (SEQ ID NO:5) and a cytoplasmic domain (SEQ ID NO:6) at the C-terminus. The mature form of human VISTA is shown in SEQ ID NO:7.The structure and function of VISTA is described e.g. in Lines et al., Cancer Res. (2014) 74(7): 1924- 1932, which is hereby incorporated by reference in its entirety. VISTA is a member of the B7 family of proteins, and is primarily expressed by leukocytes, and in particular CD14+ monocytes (including monocyte-derived suppressor cells (MDSCs)) and CD33+ myeloid cells. VISTA is also expressed by CD56+ NK cells, dendritic cells, and to a lesser extent on CD4+ and CD8+ T cells. VISTA is highly expressed on MDSCs, in particular tumor-infiltrating MDSCs, and also on tumor-infiltrating myeloid DCs (Le Mercier et al., Cancer Res. (2014) 74(7): 1933-44), as well as on tumor-associated macrophages (TAMs) and neutrophils.There is evidence that VISTA can act as both a ligand and a receptor on T cells to inhibit T cell effector function and maintain peripheral tolerance; tumors engineered to overexpress VISTA evade immune control and grow faster than tumors which do not overexpress VISTA (Wang et al., Journal of Experimental Medicine. (2011) 208 (3): 577-92; Lines et al., Cancer Res. (2014) 74(7): 1924-1932). VISTA has been shown to be a co-inhibitory receptor on CD4+ T cells or a co-inhibitory ligand for T cells. VISTA_ / _CD4+ T cells have been reported to display stronger antigen-specific proliferation and cytokine production than wildtype CD4+ T cells, suggesting that VISTA functions as an inhibitory receptor on CD4+ T cells. Blocking VISTA function using monoclonal anti-VISTA antibody has been shown toenhance infiltration, proliferation and effector function of tumor-reactive T cells within the tumor microenvironment (Le Mercier et al., Cancer Res. (2014) 74(7):1933-4).VISTA is an important immune checkpoint and therapeutic target. Recent studies have identified ligands of VISTA that regulate immune cells (Shekari, N., et al. VISTA and its ligands: the next generation of promising therapeutic targets in immunotherapy. Cancer Cell Int 23, 265 (2023)). One of these ligands is V-Set and Immunoglobulin domain containing 3 (VSIG3). VSIG3 is a member of the Ig superfamily expressed on a variety of non-hematopoietic cells, and can significantly inhibit T cell functions through the VSIG3 / VISTA pathway (Wang J, et. al. VSIG-3 as a ligand of VISTA inhibits human T-cell function. Immunology. 2019 Jan;156(1):74-85.). Another ligand of VISTA is P-selectin glycoprotein ligand-1 (PSGL-1 ). PSGL-1 is associated with the immune system and cell adhesion, and is a significant factor in the recruitment and inflammation of leukocytes (Olbromski, M., et al. The VISTA / VSIG3 / PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma. Cancer Immunol Immunother 73, 136 (2024)). VISTA has also been reported to bind to leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) (WO2019165233, WG2021047104 and Shekari, N., et al. (2023)). LRIG1 , a transmembrane protein that negatively impacts the epidermal growth factor receptor (EGFR) signaling pathway, plays a role in tumor development when its function is disrupted. It has been shown that using anti-LRIG1 mAbs disrupted the interaction between VISTA and LRIG1 and made changes in the variety of immune cells within the tumor microenvironement toward anti-tumoral responses. These immunological changes included increased proliferation of immune cells, increased polarization of M1 macrophages, and increased production of pro-inflammatory cytokines, especially IFN- y (Shekari, N., et al. (2023)).Reference herein to ‘VISTA’ generally refers to the canonical isoform of the human VISTA, but also contemplates isoforms, fragments, variants (including mutants) and homologues thereof ( / .e. from other species, e.g. non-human mammalian species (e.g. a non-human primate, e.g. rhesus, cynomolgus; e.g. a rodent, e.g. rat or mouse).A fragment of VISTA may have a minimum length of one of 10, 20, 30, 40, 50, 100, 150, 200, 250 or 300 amino acids, and may have a maximum length of one of 20, 30, 40, 50, 100, 150, 200, 250 or 300 amino acids.Isoforms, fragments, variants or homologues may optionally be functional isoforms, fragments, variants or homologues, e.g. having a functional property / activity of the reference VISTA (e.g. human VISTA), as determined by analysis by a suitable assay for the functional property / activity. For example, an isoform, fragment, variant or homologue of VISTA may e.g. display association with LRIG1 , VSIG3 and / or PSGL- 1.In some embodiments, the VISTA is VISTA from a mammal (e.g. a primate (rhesus, cynomolgus, non- human primate or human) and / or a rodent (e.g. rat or murine) VISTA). Isoforms, fragments, variants or homologues of VISTA may optionally be characterized as having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%,>94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of an immature or mature VISTA isoform from a given species, e.g. human.In some embodiments, the VISTA comprises, or consists of, an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to one of SEQ ID NOU or 7.In some embodiments, a fragment of VISTA comprises, or consists of, an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to SEQ ID NO:3, 4 or 7.VISTA has been proposed to interact with VSIG3 (IGSF11) - see e.g. Wang et al., J Immunol (2017), 198 (1 Supplement) 154.1 , which is hereby incorporated by reference in its entirety. Engagement of VSIG3 through VISTA on activated T cells inhibits T cell proliferation, and reduces production of cytokines and chemokines such as IFN-y, IL-2, IL-17, CCL5 / RANTES, CCL3 / MIP-1a, and CXCL11 / l-TAC.VSIG3 is the protein identified by UniProt Q5DX21 . Alternative splicing of mRNA encoded by the human IGSF11 gene yields three different isoforms: isoform 1 (UniProt: Q5DX21-1 , v3; SEQ ID NO:103); isoform 2 (UniProt: Q5DX21-2; SEQ ID NQ:104), which comprises a different sequence to SEQ ID NQ:103 at positions 1 to 17; and isoform 3 (UniProt: Q5DX21-3; SEQ ID NQ:105), which comprises a different sequence to SEQ ID NQ:103 at positions 1 to 17, and which also comprises a different sequence to SEQ ID NQ:103 at positions 211-235.The N-terminal 22 amino acids of SEQ ID NQs:103, 104 and 105 constitute a signal peptide, and so the mature form of VSIG3 isoforms 1 , 2 and 3 ( / .e. after processing to remove the signal peptide) have the amino acid sequences shown in SEQ ID NQs:106, 107 and 108, respectively. Positions 23 to 241 of SEQ ID NQs:103, and 104 form the extracellular domain of VSIG3 isoforms 1 and 2 (SEQ ID NOU 09), and positions 23 to 216 of SEQ ID NOU 05 form the extracellular domain of VSIG3 isoform 3 (SEQ ID NOU 10). The transmembrane domain of VSIG3 is shown in SEQ ID NOU 11 , and the cytoplasmic domain is shown in SEQ ID NOU 12. The extracellular domain comprises an Ig-like V-type domain (shown in SEQ ID NOU 13), and the extracellular domains of VSIG3 isoforms 1 and 2 additionally comprise an Ig-like C2-type domain (shown in SEQ ID NOU 14).In this specification “VSIG3” refers to VSIG3 from any species and includes VSIG3 isoforms, fragments, variants (including mutants) or homologues from any species.A fragment of VSIG3 may have a minimum length of one of 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350 or 400 amino acids, and may have a maximum length of one of 20, 30, 40, 50, 100, 150, 200, 250, 300, 350 or 400 amino acids.In some embodiments, the VSIG3 is VSIG3 from a mammal (e.g. a primate (rhesus, cynomolgous, nonhuman primate or human) and / or a rodent (e.g. rat or murine) VSIG3). Isoforms, fragments, variants or homologues of VSIG3 may optionally be characterised as having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence of an immature or mature VSIG3 isoform from a given species, e.g. human.Isoforms, fragments, variants or homologues may optionally be functional isoforms, fragments, variants or homologues, e.g. having a functional property / activity of the reference VSIG3, as determined by analysis by a suitable assay for the functional property / activity. For example, an isoform, fragment, variant or homologue of VSIG3 may e.g. display association with VISTA.In some embodiments, the VSIG3 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to one of SEQ ID NOs:103 to 108. In some embodiments, a fragment of VSIG3 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to one of SEQ ID NOs:106 to 110, 113 or 114.VISTA has also been proposed to interact with PSGL-1 - see e.g. WO 2018 / 132476 A1 . Johnston et al., Nature (2019) 574: 565-570 discloses that PSGL-1 associates with VISTA via interaction involving positions Y46, Y48, Y51 , E56 and T57 of PSGL-1 , and positions H98, H100, H153, H154 and H155 of VISTA.PSGL-1 isoform 1 is the protein identified by UniProt Q14242-1 (SEQ ID NO:115). PSGL-1 isoform 2 is the protein identified by UniProt Q14242-2 (SEQ ID NOU 16), and differs from PSGL-1 isoform 1 in that it comprises an additional 16 amino acids after position 1 of SEQ ID NOU 15.The N-terminal 17 amino acids of SEQ ID NOU 15 constitutes a signal peptide, and so the mature form of PSGL-1 ( / .e. after processing to remove the signal peptide) has the amino acid sequence shown in SEQ ID NOU 17. Positions 18 to 320 of SEQ ID NOU 15 form the extracellular domain of PSGL-1 (SEQ ID NOU 18). The transmembrane domain of PSGL-1 is shown in SEQ ID NOU 19, and the cytoplasmic domain is shown in SEQ ID NOU 20. The extracellular domain comprises 12, 10 amino acid tandem repeats; the repeat region is shown in SEQ ID NO:121.In this specification “PSGL-1” refers to PSGL-1 from any species and includes PSGL-1 isoforms, fragments, variants (including mutants) or homologues from any species.A fragment of PSGL-1 may have a minimum length of one of 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350 or 400 amino acids, and may have a maximum length of one of 20, 30, 40, 50, 100, 150, 200, 250, 300, 350 or 400 amino acids.In some embodiments, the PSGL-1 is PSGL-1 from a mammal (e.g. a primate (rhesus, cynomolgous, non-human primate or human) and / or a rodent (e.g. rat or murine) PSGL-1 ). Isoforms, fragments, variants or homologues of PSGL-1 may optionally be characterised as having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence of an immature or mature PSGL-1 isoform from a given species, e.g. human.Isoforms, fragments, variants or homologues may optionally be functional isoforms, fragments, variants or homologues, e.g. having a functional property / activity of the reference PSGL-1 , as determined by analysis by a suitable assay for the functional property / activity. For example, an isoform, fragment, variant or homologue of PSGL-1 may e.g. display association with VISTA.In some embodiments, the PSGL-1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:115 or 116. In some embodiments, a fragment of PSGL-1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to one of SEQ ID NOs:117, 118 or 121.VISTA has also been proposed to interact with LRIG1 - see e.g. WO / 2019 / 165233 A1 . WO / 2019 / 165233 A1 discloses that LRIG1 associates with VISTA via interaction involving positions 245 to 260 of LRIG1 , and positions 68 to 92 of VISTA.LRIG1 isoform 1 is the protein identified by UniProt Q96JA1-1 (SEQ ID NO:122). LRIG1 isoform 2 is the protein identified by UniProt Q96JA1-2 (SEQ ID NOU 24), and differs from LRIG1 isoform 1 in that it comprises an additional 14 amino acids after position 387 of SEQ ID NOU 22, and in that positions 644 to 691 of SEQ ID NO:122 are instead Q.The N-terminal 34 amino acids of SEQ ID NO:122 constitutes a signal peptide, and so the mature form of LRIG1 isoforms 1 and 2 ( / .e. after processing to remove the signal peptide) have the amino acid sequences shown in SEQ ID NOs:123 and 125, respectively. The extracellular domain of LRIG1 isoform 1 is shown in SEQ ID NO:126, and the extracellular domain of LRIG1 isoform 2 is shown in SEQ ID NO:127. The transmembrane domain of LRIG1 is shown in SEQ ID NO:128, and the cytoplasmic domain is shown in SEQ ID NO:129. The extracellular domain comprises 15, leucine-rich repeats, followed by three Ig-like domains proximal to the transmembrane domain (see e.g. Xu et al. J Mol Biol. (2015) 427(10): 1934-1948).In this specification “LRIG1” refers to LRIG1 from any species and includes LRIG1 isoforms, fragments, variants (including mutants) or homologues from any species.A fragment of LRIG1 may have a minimum length of one of 10, 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 500, 600 or 700 amino acids, and may have a maximum length of one of 20, 30, 40, 50, 100, 150, 200, 250, 300, 350, 400, 500, 600 or 700 amino acids.In some embodiments, the LRIG1 is LRIG1 from a mammal (e.g. a primate (rhesus, cynomolgus, nonhuman primate or human) and / or a rodent (e.g. rat or murine) LRIG1 ). Isoforms, fragments, variants or homologues of LRIG1 may optionally be characterised as having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to the amino acid sequence of an immature or mature LRIG1 isoform from a given species, e.g. human.Isoforms, fragments, variants or homologues may optionally be functional isoforms, fragments, variants or homologues, e.g. having a functional property / activity of the reference LRIG1 , as determined by analysis by a suitable assay for the functional property / activity. For example, an isoform, fragment, variant or homologue of LRIG1 may e.g. display association with VISTA.In some embodiments, the LRIG1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:122, 123, 124 or 125. In some embodiments, a fragment of LRIG1 comprises, or consists of, an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to one of SEQ ID NOs:126 or 127.Antigen-binding molecules and antigen-binding moietiesAn ‘antigen-binding molecule’ refers to a molecule that binds to a given target antigen. Antigen-binding molecules comprise one or more antigen-binding moieties through which the antigen-binding molecule binds to its target antigen(s). The antigen-binding molecules of the present disclosure comprise an antigen-binding moiety that binds to VISTA ( / .e. a VISTA-binding moiety). In some embodiments, the antigen-binding molecules comprise an antigen-binding polypeptide complex comprising an antigenbinding moiety that binds to VISTA.Antigen-binding moieties may comprise, or may be derived from, antibodies ( / .e. immunoglobulins (Igs)) and antigen-binding fragments of antibodies. As used herein, ‘antibodies’ include monoclonal antibodies, polyclonal antibodies, monospecific and multispecific (e.g., bispecific, trispecific, etc.) antibodies, and antibody-derived antigen-binding molecules such as scFv, scFab, diabodies, triabodies, scFv-Fc, minibodies, single domain antibodies (e.g. VhH, etc.). Antigen-binding fragments of antibodies include e.g. Fv, Fab, F(ab’)2 and F(ab’) fragments.In some embodiments, an antigen-binding moiety according to the present disclosure comprises, or consists of, the antigen-binding region of an antibody (e.g. an antigen-binding fragment of an antibody). Antigen-binding moieties may be derived from antibodies. Antibody-derived antigen-binding moieties may comprise, or consist of, the antigen-binding region of an antibody (e.g. an antigen-binding fragment of anantibody). In some embodiments, an antigen-binding moiety may be or comprise the Fv (e.g. provided as an scFv) or the Fab region of an antibody that binds to a given target antigen, or the whole antibody.The antigen-binding moieties of the present disclosure may be designed and prepared using the sequences of monoclonal antibodies (mAbs) capable of binding to VISTA. Antigen-binding regions of antibodies, such as variable fragment (Fv), Fab and F(ab’)2 fragments may also be used / provided. An ‘antigen-binding region’ is any fragment of an antibody that binds to the target for which the given antibody is specific.In some embodiments, an antigen-binding moiety comprises the antibody heavy chain variable region (VH) and the antibody light chain variable region (VL) of an antibody capable of specific binding to VISTA. In some embodiments, the antigen-binding moiety is or comprises the Fv (e.g. provided as an scFv) of an antibody. In some embodiments, the antigen-binding moiety is or comprises the Fab region of an antibody. In some embodiments, the antigen-binding moiety is or comprises the whole antibody ( / .e. comprising variable and constant regions).An antigen-binding moiety may be, or may comprise, an antigen-binding polypeptide, or an antigenbinding polypeptide complex. An antigen-binding moiety may comprise more than one polypeptide which together form an antigen-binding moiety. The polypeptides may associate covalently or non-covalently. In some embodiments, the polypeptides form part of a larger polypeptide comprising the polypeptides (e.g. in the case of scFv comprising VH and VL, or in the case of scFab comprising VH-CH1 and VL-CL).In some embodiments, an antigen-binding moiety according to the present disclosure comprises, or consists of, a polypeptide complex formed by protein: protein interaction between constituent peptides / polypeptides of the antigen-binding moiety. An antigen-binding moiety may refer to a non- covalent or covalent complex of more than one polypeptide (e.g. 2, 3, 4, 6, or 8 polypeptides), e.g. an IgG-like antigen-binding moiety comprising two heavy chain polypeptides and two light chain polypeptides.Antibodies generally comprise six complementarity-determining regions CDRs; three in the heavy chain variable (VH) region: HC-CDR1 , HC-CDR2 and HC-CDR3, and three in the light chain variable (VL) region: LC-CDR1 , LC-CDR2, and LC-CDR3. The six CDRs together define the paratope of the antibody, which is the part of the antibody that binds to the target antigen.The VH region and VL region comprise framework regions (FRs) either side of each CDR, which provide a scaffold for the CDRs. From N-terminus to C-terminus, VH regions comprise the following structure: N term-[HC-FR1]-[HC-CDR1]-[HC-FR2]-[HC-CDR2]-[HC-FR3]-[HC-CDR3]-[HC-FR4]-C term; and VL regions comprise the following structure: N term-[LC-FR1]-[LC-CDR1]-[LC-FR2]-[LC-CDR2]-[LC-FR3]- [LC-CDR3]-[LC-FR4]-C term.There are several different conventions for defining antibody CDRs and FRs, such as those described in Kabat et al., Sequences of Proteins of Immunological Interest, 5thEd. Public Health Service, NationalInstitutes of Health, Bethesda, MD (1991), Chothia et a!., J. Mol. Biol. 196:901-917 (1987), and VBASE2, as described in Retter et al., Nucl. Acids Res. (2005) 33 (suppl 1): D671-D674. The CDRs and FRs of the VH regions and VL regions of the antibody clones described herein were defined according to the international IMGT (ImMunoGeneTics) information system (LeFranc et al., Nucleic Acids Res. (2015) 43 (Database issue):D413-22), which uses the IMGT V-DOMAIN numbering rules as described in Lefranc et al., Dev. Comp. Immunol. (2003) 27:55-77. In preferred embodiments, the CDRs and FRs of antigenbinding moieties referred to herein are defined according to the IMGT information system.In some embodiments, an antigen-binding moiety according to the present disclosure comprises, or consists of, an Fv region that binds to VISTA. In some embodiments, the VH and VL regions of the Fv are provided as single polypeptide joined by a linker sequence, i.e. a single chain Fv (scFv).The VL and light chain constant (CL) region, and the VH region and heavy chain constant 1 (CH1) region of an antigen-binding region of an antibody together constitute the Fab region. In some embodiments, the antigen-binding moiety comprises a Fab region comprising a VH, a CH1 , a VL and a CL (e.g. CK or CA). In some embodiments, the Fab region comprises a polypeptide comprising a VH and a CH1 (e.g. a VH- CH1 fusion polypeptide), and a polypeptide comprising a VL and a CL (e.g. a VL-CL fusion polypeptide). In some embodiments, the Fab region comprises a polypeptide comprising a VH and a CL (e.g. a VH-CL fusion polypeptide) and a polypeptide comprising a VL and a CH1 (e.g. a VL-CH1 fusion polypeptide); that is, in some embodiments, the Fab region is a CrossFab region. In some embodiments, the VH, CH1 , VL and CL regions of the Fab or CrossFab are provided as single polypeptide joined by linker regions, i.e. as a single chain Fab (scFab) or a single chain CrossFab (scCrossFab).In some embodiments, an antigen-binding moiety described herein comprises, or consists of, a whole antibody which binds to VISTA. As used herein, ‘whole antibody’ refers to an antibody having a structure which is substantially similar to the structure of an immunoglobulin (Ig). Different kinds of immunoglobulins and their structures are described e.g. in Schroeder and Cavacini J Allergy Clin Immunol. (2010) 125(202): S41-S52, which is hereby incorporated by reference in its entirety.Immunoglobulins of type G (i.e. IgG) are -150 kDa glycoproteins comprising two heavy chains and two light chains. From N- to C-terminus, the heavy chains comprise a VH followed by a heavy chain constant region comprising three constant domains (CH1 , CH2, and CH3), and similarly the light chains comprise a VL followed by a CL. Depending on the heavy chain, immunoglobulins may be classed as IgG (e.g.IgG 1 , lgG2, lgG3, lgG4), IgA (e.g. lgA1 , lgA2), IgD, Ig E, or IgM. The light chain may be kappa (K) or lambda (A).In some embodiments, the antigen-binding moiety comprises, or consists of, an IgG (e.g. lgG1 , lgG2, lgG3, lgG4), IgA (e.g. lgA1 , lgA2), IgD, IgE, or IgM which binds to the relevant target antigen (i.e. VISTA).In some embodiments, an antigen-binding moiety of the present disclosure comprises one or more regions (e.g. CH1 , hinge, CH2, CH3, etc.) of an immunoglobulin heavy chain constant sequence. In some embodiments, the immunoglobulin heavy chain constant sequence is, or is derived from, the heavy chainconstant sequence of an IgG (e.g. IgG 1 , lgG2, lgG3, lgG4), IgA (e.g. lgA1 , lgA2), IgD, IgE or IgM, e.g. a human IgG (e.g. hlgG 1 , hlgG2, hlgG3, hlgG4), hlgA (e.g. hlgA1 , hlgA2), hlgD, hlgE or hlgM. In some embodiments, the immunoglobulin heavy chain constant sequence is, or is derived from, the heavy chain constant sequence of a human lgG1 allotype (e.g. G1 m1 , G1 m2, G1 m3 or G1 m17). In some embodiments, the immunoglobulin heavy chain constant sequence is, or is derived from human lgG4. In some embodiments, the immunoglobulin heavy chain constant sequence is, or is derived from human lgG4 comprising the substitution S228P (EU numbering).In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:19. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:20 or 24. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:21 or 36. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:22. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:25 or 39. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:18, 23 or 34.In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:9 or 14. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NQ:10. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acidsequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:11 or 35. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:12 or 15. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:16, 17, 37 or 38. In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:8, 13, 32 or 33.In some embodiments, an antigen-binding moiety of the present disclosure comprises one or more regions of an immunoglobulin light chain constant sequence. In some embodiments, the immunoglobulin light chain constant sequence is human immunoglobulin kappa constant (IGKC; CK). In some embodiments, the immunoglobulin light chain constant sequence is a human immunoglobulin lambda constant (IGLC; CA), e.g. IGLC1 , IGLC2, IGLC3, IGLC6 or IGLC7.In some embodiments, an antigen-binding moiety comprises one or more polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:26, 27, 28, 29, 30, or 31.In some embodiments described herein, one or more amino acids of an amino acid sequence referred to herein (e.g. an amino acid sequence of an antigen-binding moiety, e.g. an amino acid sequence of a CDR or VH / VL region) are substituted with another amino acid. A substitution comprises substitution of an amino acid residue with a non-identical ‘replacement’ amino acid residue. A replacement amino acid residue of a substitution according to the present disclosure may be a naturally-occurring amino acid residue (i.e. encoded by the genetic code) which is non-identical to the amino acid residue at the relevant position of the equivalent, unsubstituted amino acid sequence, selected from: alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gin), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (He): leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Vai). In some embodiments, a replacement amino acid may be a non-naturally occurring amino acid residue - i.e. an amino acid residue other than those recited in the preceding sentence. Examples of non-naturally occurring amino acid residues include norleucine, ornithine, norvaline, homoserine, aib, and other amino acid residue analogues such as those described in Ellman, et al., Meth. Enzym. 202 (1991 ) 301-336.In some embodiments, a substitution may be biochemically conservative. In some embodiments, where an amino acid to be substituted is provided in one of rows 1 to 5 of the table below, the replacement amino acid of the substitution is another, non-identical amino acid provided in the same row:By way of illustration, in some embodiments wherein substitution is of a Met residue, the replacement amino acid may be selected from Ala, Vai, Leu, He, Trp, Tyr, Phe and Norleucine. In some embodiments, a replacement amino acid in a substitution may have the same side chain polarity as the amino acid residue it replaces. In some embodiments, a replacement amino acid in a substitution may have the same side chain charge (at pH 7.4) as the amino acid residue it replaces:That is, in some embodiments, a nonpolar amino acid is substituted with another, non-identical nonpolar amino acid. In some embodiments, a polar amino acid is substituted with another, non-identical polar amino acid. In some embodiments, an acidic polar amino acid is substituted with another, non-identical acidic polar amino acid. In some embodiments, a basic polar amino acid is substituted with another, non- identical basic polar amino acid. In some embodiments, a neutral amino acid is substituted with another, non-identical neutral amino acid. In some embodiments, a positive amino acid is substituted with another, non-identical positive amino acid. In some embodiments, a negative amino acid is substituted with another, non-identical negative amino acid.In some embodiments, substitution(s) may be functionally conservative. That is, in some embodiments, the substitution may not affect (or may not substantially affect) one or more functional properties (e.g. target binding) of the antigen-binding moiety comprising the substitution as compared to the equivalent unsubstituted molecule.It will be appreciated that the antigen-binding molecules of the present disclosure could be formulated as multispecific antigen-binding molecules. By ‘multispecific’ it is meant that the antigen-binding molecule binds to more than one target antigen (e.g. one of 2, 3, 4, 5, 6 or more target antigens). In some embodiments, the antigen-binding molecule is a bispecific antigen-binding molecule. In some embodiments, the antigen-binding molecule comprises at least two, different antigen-binding moieties. In some embodiments, the antigen-binding molecule comprises at least two antigen-binding moieties, wherein each antigen-binding moiety binds to a different target antigen.In some embodiments, the antigen-binding molecules of the present disclosure display at least monovalent binding with respect to VISTA. Binding valency refers to the number of binding sites in an antigen-binding molecule for a given antigenic determinant. Accordingly, in some embodiments, the antigen-binding molecule comprises at least one binding site for VISTA.Multispecific antigen-binding molecules may be provided in any suitable format, such as those formats described in described in Brinkmann and Kontermann, MAbs (2017) 9(2): 182-212, which is hereby incorporated by reference in its entirety. Multispecific antigen-binding molecule formats include those shown in Figure 2 of Brinkmann and Kontermann, MAbs (2017) 9(2): 182-212: antibody conjugates, e.g. lgG2, F(ab’)2 or CovX-Body; IgG or IgG-like molecules, e.g. IgG, chimeric IgG, KA-body common HC; CH1 / CL fusion proteins, e.g. scFv2-CH1 / CL, VHH2-CH1 / CL; ‘variable domain only’ bispecific antigenbinding molecules, e.g. tandem scFv (taFV), triplebodies, diabodies (Db), dsDb, Db(kih), DART, scDB, dsFv-dsFv, tandAbs, triple heads, tandem dAb / VHH, tetravalent dAb.VHH; Non-lg fusion proteins, e.g. scFv2-albumin, scDb-albumin, taFv-albumin, taFv-toxin, miniantibody, DNL-Fab2, DNL-Fab2-scFv, DNL- Fab2-lgG-cytokine2, ImmTAC (TCR-scFv); modified Fc and CH3 fusion proteins, e.g. scFv-Fc(kih), scFv-Fc(CH3 charge pairs), scFv-Fc (EW-RVT), scFv-fc (HA-TF), scFv-Fc (SEEDbody), taFv-Fc(kih), scFv- Fc(kih)-Fv, Fab-Fc(kih)-scFv, Fab-scFv-Fc(kih), Fab-scFv-Fc(BEAT), Fab-scFv-Fc (SEEDbody), DART- Fc, scFv-CH3(kih), TriFabs; Fc fusions, e.g. Di-diabody, scDb-Fc, taFv-Fc, scFv-Fc-scFv, HCAb-VHH, Fab-scFv-Fc, scFv4-lg, scFv2-Fcab; CH3 fusions, e.g. Dia-diabody, scDb-CH3; IgE / IgM CH2 fusions, e.g. scFv-EHD2-scFv, scFvMHD2-scFv; Fab fusion proteins, e.g. Fab-scFv (bibody), Fab-scFv2 (tribody), Fab- Fv, Fab-dsFv, Fab-VHH, orthogonal Fab-Fab; non-lg fusion proteins, e.g. DNL-Fabs, DNL-Fab2-scFv, DNL-Fab2-lgG-cytokine2; asymmetric IgG or IgG-like molecules, e.g. IgG(kih), IgG(kih) common LC, ZW1 IgG common LC, Biclonics common LC, CrossMab, CrossMab(kih), scFab-lgG(kih), Fab-scFab-lgG(kih), orthogonal Fab IgG(kih), DuetMab, CH3 charge pairs + CH1 / CL charge pairs, hinge / CH3 charge pairs, SEED-body, Duobody, four-in-one-CrossMab(kih), LUZ-Y common LC; LUZ-Y scFab-IgG, FcFc*; appended and Fc-modified IgGs, e.g. lgG(kih)-Fv, IgG HA-TF-Fv, lgG(kih)scFab, scFab-Fc(kih)-scFv2, scFab-Fc(kih)-scFv, half DVD-lg, DVI-lg (four-in-one), CrossMab-Fab; modified Fc and CH3 fusion proteins, e.g. Fab-Fc(kih)-scFv, Fab-scFv-Fc(kih), Fab-scFv-Fc(BEAT), Fab-scFv-Fc-SEEDbody, TriFab; appended IgGs - HC fusions, e.g. IgG-HC, scFv, IgG-dAb, IgG-taFV, IgG-CrossFab, IgG-orthogonal Fab, IgG-(CaCP) Fab, scFv-HC-IgG, tandem Fab-IgG (orthogonal Fab), Fab-lgG(CaCp Fab), Fab-lgG(CR3), Fab-hinge-lgG(CR3); appended IgGs - LC fusions, e.g. IgG-scFv(LC), scFv(LC)-lgG, dAb-IgG; appended IgGs - HC and LC fusions, e.g. DVD-lg, TVD-lg, CODV-lg, scFv4-lgG, Zybody; Fc fusions, e.g. Fab-scFv- Fc, scFv4-lg; F(ab’)2 fusions, e.g. F(ab’)2-scFv2; CH1 / CL fusion proteins e.g. scFv2-CH1-hinge / CL; modified IgGs, e.g. DAF (two-in one-IgG), DutaMab, Mab2; and non-lg fusions, e.g. DNL-Fab4-lgG.The present disclosure also provides Chimeric Antigen Receptors (CARs) comprising the antigen-binding molecules / polypeptides / polypeptide complexes of the present disclosure.CARs are recombinant receptors that provide both antigen-binding and T cell activating functions. CAR structure and engineering is reviewed, for example, in Dotti et al., Immunol Rev (2014) 257(1), hereby incorporated by reference in its entirety. CARs comprise an antigen-binding moiety linked to a cell membrane anchor region and a signalling region. An optional hinge region may provide separation between the antigen-binding region and cell membrane anchor region, and may act as a flexible linker.The CAR of the present disclosure comprises an antigen-binding moiety which comprises or consists of an antigen-binding polypeptide or an antigen-binding polypeptides / polypeptide complexes of the present disclosure. Thus, in some aspects and embodiments, an antigen-binding molecule according to the present disclosure is a CAR.The cell membrane anchor region is provided between the antigen-binding region and the signalling region of the CAR and provides for anchoring the CAR to the cell membrane of a cell expressing a CAR, with the antigen-binding region in the extracellular space, and signalling region inside the cell. In some embodiments, the CAR comprises a cell membrane anchor region comprising or consisting of an amino acid sequence which comprises, consists of, or is derived from, the transmembrane region amino acid sequence for one of CD3- , CD4, CD8 or CD28. As used herein, a region which is ‘derived from’ a reference amino acid sequence comprises an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%,>92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the reference sequence.The signalling region of a CAR allows for activation of the T cell. The CAR signalling regions may comprise the amino acid sequence of the intracellular domain of CD3- , which provides immunoreceptor tyrosine-based activation motifs (ITAMs) for phosphorylation and activation of the CAR-expressing T cell. Signalling regions comprising sequences of other ITAM-containing proteins such as FcyRI have also been employed in CARs (Haynes et al., 2001 J Immunol 166(1 ):182-187). Signalling regions of CARs may also comprise co-stimulatory sequences derived from the signalling region of co-stimulatory molecules, to facilitate activation of CAR-expressing T cells upon binding to the target protein. Suitable co-stimulatory molecules include CD28, 0X40, 4-1 BB, ICOS and CD27. In some cases CARs are engineered to provide for co-stimulation of different intracellular signalling pathways. For example, signalling associated with CD28 costimulation preferentially activates the phosphatidylinositol 3-kinase (PI3K) pathway, whereas the 4-1 BB-mediated signalling is through TNF receptor associated factor (TRAF) adaptor proteins. Signalling regions of CARs therefore sometimes contain co-stimulatory sequences derived from signalling regions of more than one co-stimulatory molecule. In some embodiments, the CAR of the present disclosure comprises one or more co-stimulatory sequences comprising or consisting of an amino acid sequence which comprises, consists of, or is derived from, the amino acid sequence of the intracellular domain of one or more of CD28, 0X40, 4-1 BB, ICOS and CD27.An optional hinge region may provide separation between the antigen-binding domain and the transmembrane domain, and may act as a flexible linker. Hinge regions may be derived from IgG 1 . In some embodiments, the CAR of the present disclosure comprises a hinge region comprising or consisting of an amino acid sequence which comprises, consists of, or is derived from, the amino acid sequence of the hinge region of IgG 1 .The antigen-binding moiety of the CAR of the present disclosure may be provided with any suitable format, e.g. scFv, scFab, etc.VISTA-bindinq moietiesThe antigen-binding molecules of the present disclosure comprise an antigen-binding moiety that binds to VISTA.In some embodiments, the antigen-binding moiety comprises the CDRs of an antigen-binding moiety which is capable of binding to VISTA. In some embodiments, the antigen-binding moiety comprises the FRs of an antigen-binding moiety which is capable of binding to VISTA. In some embodiments, the antigen-binding moiety comprises the CDRs and the FRs of an antibody that is capable of binding to VISTA. That is, in some embodiments the antigen-binding moiety comprises the VH region and the VL region of an antibody that is capable of binding to VISTA.In some embodiments, an antigen-binding moiety which is capable of binding to VISTA according to the present disclosure may be, or may be derived from, 9M2-C12 (described e.g. in WO 2019 / 185879 A1 and WO 2023 / 046979 A1).In some embodiments, the antigen-binding moiety is capable of binding to a polypeptide comprising, or consisting of, the amino acid sequence of one of SEQ ID NOs:1 , 3, 4 or 7.In embodiments where the antigen binding moiety is capable of binding to a peptide / polypeptide comprising a reference amino acid sequence, the peptide / polypeptide may comprise one or more additional amino acids at one or both ends of the reference amino acid sequence. In some embodiments the peptide / polypeptide comprises e.g. 1-5, 1-10, 1-20, 1-30, 1-40, 1-50, 5-10, 5-20, 5-30, 5-40, 5-50, IQ- 20, 10-30, 10-40, 10-50, 20-30, 20-40 or 20-50 additional amino acids at one or both ends of the reference amino acid sequence. In some embodiments the additional amino acid(s) provided at one or both ends ( / .e. the N-terminal and C-terminal ends) of the reference sequence correspond to the positions at the ends of the reference sequence in the context of the amino acid sequence of VISTA.In some embodiments, the antigen-binding moiety comprises the heavy chain CDRs and the light chain CDRs of a VISTA-binding antibody described herein. In some embodiments, the antigen-binding moiety comprises the VH and VL of a VISTA-binding antibody described herein. In some embodiments, the antigen-binding moiety comprises the heavy chain polypeptide ( / .e. comprising VH, CH1 , CH2 and CH3 region sequences) and light chain polypeptide ( / .e. comprising VL and CL region sequences) of a VISTA- binding antibody described herein.In some embodiments, the antigen-binding moiety comprises the heavy chain CDRs and the light chain CDRs of anti-VISTA antibody V9-4K. In some embodiments, the antigen-binding moiety comprises the VH and VL of V9-4K. In some embodiments, the antigen-binding moiety comprises the heavy chain polypeptide ( / .e. comprising VH, CH1 , CH2 and CH3 region sequences) and light chain polypeptide ( / .e. comprising VL and CL region sequences) of V9-4K.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises a VH region of one of (1) to (5) below:(1) a VH region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NO:42 HC-CDR3 having the amino acid sequence of SEQ ID NO:43, or a variant thereof in which 1 or 2 or 3 amino acids in HC-CDR1 , and / or in which 1 or 2 or 3 amino acids in HC-CDR2, and / or in which 1 or 2 or 3 amino acids in HC-CDR3 are substituted with another amino acid.(2) a VH region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70HC-CDR3 having the amino acid sequence of SEQ ID NO:76, or a variant thereof in which 1 or 2 or 3 amino acids in HC-CDR1 , and / or in which 1 or 2 or 3 amino acids in HC-CDR2, and / or in which 1 or 2 or 3 amino acids in HC-CDR3 are substituted with another amino acid.(3) a VH region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41HC-CDR2 having the amino acid sequence of SEQ ID NQ:70HC-CDR3 having the amino acid sequence of SEQ ID NO:71 , or a variant thereof in which 1 or 2 or 3 amino acids in HC-CDR1 , and / or in which 1 or 2 or 3 amino acids in HC-CDR2, and / or in which 1 or 2 or 3 amino acids in HC-CDR3 are substituted with another amino acid.(4) a VH region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41HC-CDR2 having the amino acid sequence of SEQ ID NQ:70HC-CDR3 having the amino acid sequence of SEQ ID NO:72, or a variant thereof in which 1 or 2 or 3 amino acids in HC-CDR1 , and / or in which 1 or 2 or 3 amino acids in HC-CDR2, and / or in which 1 or 2 or 3 amino acids in HC-CDR3 are substituted with another amino acid.(5) a VH region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41HC-CDR2 having the amino acid sequence of SEQ ID NQ:70HC-CDR3 having the amino acid sequence of SEQ ID NO:73, or a variant thereof in which 1 or 2 or 3 amino acids in HC-CDR1 , and / or in which 1 or 2 or 3 amino acids in HC-CDR2, and / or in which 1 or 2 or 3 amino acids in HC-CDR3 are substituted with another amino acid.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises a VH region of one of (6) to (10) below:(6) a VH region incorporating the following FRs:HC-FR1 having the amino acid sequence of SEQ ID NO:44HC-FR2 having the amino acid sequence of SEQ ID NO:45HC-FR3 having the amino acid sequence of SEQ ID NO:46HC-FR4 having the amino acid sequence of SEQ ID NO:47, or a variant thereof in which one or two or three amino acids in one or more of HC-FR1 , HC-FR2, HC-FR3, or HC-FR4 are substituted with another amino acid;(7) a VH region incorporating the following FRs:HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:77HC-FR4 having the amino acid sequence of SEQ ID NO:60, or a variant thereof in which one or two or three amino acids in one or more of HC-FR1 , HC-FR2, HC-FR3, or HC-FR4 are substituted with another amino acid.(8) a VH region incorporating the following FRs:HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:59HC-FR4 having the amino acid sequence of SEQ ID NQ:60, or a variant thereof in which one or two or three amino acids in one or more of HC-FR1 , HC-FR2, HC-FR3, or HC-FR4 are substituted with another amino acid.(9) a VH region incorporating the following FRs:HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:74HC-FR4 having the amino acid sequence of SEQ ID NQ:60, or a variant thereof in which one or two or three amino acids in one or more of HC-FR1 , HC-FR2, HC-FR3, or HC-FR4 are substituted with another amino acid.(10) a VH region incorporating the following FRs:HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:75HC-FR4 having the amino acid sequence of SEQ ID NQ:60, or a variant thereof in which one or two or three amino acids in one or more of HC-FR1 , HC-FR2, HC-FR3, or HC-FR4 are substituted with another amino acid.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises a VH region comprising the CDRs according to any one of (1 ) to (5), and the FRs according to any one of (6) to (10) above.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises:(11 ) a VH region comprising the CDRs according to (1 ) and the FRs according to (6);(12) a VH region comprising the CDRs according to (1) and the FRs according to (7) or (8);(13) a VH region comprising the CDRs according to (2) and the FRs according to (7), (9) or (10);(14) a VH region comprising the CDRs according to (3) and the FRs according to (7), (9) or (10);(15) a VH region comprising the CDRs according to (4) and the FRs according to (7) or (10); or(16) a VH region comprising the CDRs according to (5) and the FRs according to (7) or (10).In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises one of the following VH regions:(17) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:40;(18) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:56;(19) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:66;(20) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:67;(21 ) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:68; or(22) a VH region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:69.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises:(23) a VL region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49LC-CDR2 having the amino acid sequence of SEQ ID NQ:50LC-CDR3 having the amino acid sequence of SEQ ID NO:51 , or a variant thereof in which 1 or 2 or 3 amino acids in LC-CDR1 , and / or in which 1 or 2 or 3 amino acids in LC-CDR2, and / or in which 1 or 2 or 3 amino acids in LC-CDR3 are substituted with another amino acid.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises:(24) a VL region incorporating the following FRs:LC-FR1 having the amino acid sequence of SEQ ID NO:52LC-FR2 having the amino acid sequence of SEQ ID NO:53LC-FR3 having the amino acid sequence of SEQ ID NO:54LC-FR4 having the amino acid sequence of SEQ ID NO:55, or a variant thereof in which one or two or three amino acids in one or more of LC-FR1 , LC-FR2, LC-FR3, or LC-FR4 are substituted with another amino acid; or(25) a VL region incorporating the following FRs:LC-FR1 having the amino acid sequence of SEQ ID NO:62LC-FR2 having the amino acid sequence of SEQ ID NO:63LC-FR3 having the amino acid sequence of SEQ ID NO:64LC-FR4 having the amino acid sequence of SEQ ID NO:65, or a variant thereof in which one or two or three amino acids in one or more of LC-FR1 , LC-FR2, LC-FR3, or LC-FR4 are substituted with another amino acid.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises a VL region comprising the CDRs according to (23), and the FRs according to (24) or (25) above.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises:(26) a VL region comprising the CDRs according to (23) and the FRs according to (24); or(27) a VL region comprising the CDRs according to (23) and the FRs according to (25).In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises one of the following VL regions:(28) a VL region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:48; or(29) a VL region comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:61.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises a VH region according to any one of (1) to (22) above, and a VL region according to any one of (23) to (29) above.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region incorporating HC-CDR1 , HC-CDR2 and HC-CDR3 from column A of Table A; and / or a VL regionincorporating LC-CDR1 , LC-CDR2 and LC-CDR3 from column B of Table A. In some embodiments, the VH and VL regions are selected from the same row of Table A.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region incorporating HC-FR1 , HC-FR2, HC-FR3 and HC-FR4 from column A of Table B; and / or a VL region incorporating LC-FR1 , LC-FR2, LC-FR3 and LC-FR4 from column B of Table B. In some embodiments, the VH and VL regions are selected from the same row of Table B.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of a VH region selected from column A of Table C; and / or a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of a VL region selected from column B of Table C. In some embodiments, the VH and VL regions are selected from the same row of Table C.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:56; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NQ:40; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:48.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:66; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:67; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:68; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:69; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:61 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises: a VH region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NO:99; and a VL region comprising an amino acid sequence having at least 60% sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% sequence identity to the amino acid sequence of SEQ ID NQ:101 .In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:83, 84 or 85; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:84; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:86, 87 or 88; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:89, 90 or 91 ; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:92, 93 or 94; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91 %, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:95, 96 or 97; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:98.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:79, 80 or 81 ; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:82.In some embodiments, the VISTA-binding antigen-binding molecule / moiety comprises, or consists of:(i) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NQ:100; and / or(ii) one or more polypeptides comprising, or consisting of, an amino acid sequence having at least 70% sequence identity, more preferably one of >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NQ:102.In some embodiments, the antigen-binding molecule of the present disclosure comprises: (i) a polypeptide comprising or consisting of an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to an amino acid sequence indicated in column A of Table D, and / or (ii) a polypeptide comprising or consisting of an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to an amino acid sequence indicated in column B of Table D, wherein the sequences of columns A and B are selected from the same row of Table D.In some embodiments, the antigen-binding molecule of the present disclosure comprises one or more of the polypeptides of an antigen-binding molecule according to Table D herein. That is, in some embodiments, the antigen-binding molecule comprises: (i) a polypeptide comprising or consisting of an amino acid sequence indicated in column A of Table D, and / or (ii) a polypeptide comprising or consistingof an amino acid sequence indicated in column B of Table D, wherein the sequences of columns A and B are selected from the same row of Table D.Fc regionsIn some embodiments, the antigen-binding molecules of the present disclosure comprise an Fc region. As used herein, an ‘Fc region’ refers to a polypeptide complex formed by interaction between two polypeptides, each polypeptide comprising the CH2-CH3 region of an immunoglobulin (Ig) heavy chain constant sequence.Herein, a ‘CH2 domain’ refers to an amino acid sequence corresponding to the CH2 domain of an immunoglobulin (Ig). The CH2 domain is the region of an Ig formed by positions 231 to 340 of the immunoglobulin constant domain, according to the EU numbering system described in Edelman et al., Proc Natl Acad Sci USA (1969) 63(1): 78-85. A ‘CH3 domain’ refers to an amino acid sequence corresponding to the CH3 domain of an immunoglobulin (Ig). The CH3 domain is the region of an Ig formed by positions 341 to 447 of the immunoglobulin constant domain, according to the EU numbering system described in Edelman et al., Proc Natl Acad Sci USA (1969) 63(1): 78-85. A ‘CH2-CH3 region’ refers to an amino acid sequence corresponding to the CH2 and CH3 domains of an immunoglobulin (Ig). The CH2-CH3 region is the region of an Ig formed by positions 231 to 447 of the immunoglobulin constant domain, according to the EU numbering system described in Edelman et al., Proc Natl Acad Sci USA (1969) 63(1): 78-85.In some embodiments, a CH2 domain, CH3 domain and / or a CH2-CH3 region according to the present disclosure corresponds to the CH2 domain / CH3 domain / CH2-CH3 region of an IgG (e.g. IgG 1 , lgG2, lgG3, lgG4), IgA (e.g. lgA1 , lgA2), IgD, IgE or IgM. In some embodiments, the CH2 domain, CH3 domain and / or a CH2-CH3 region corresponds to the CH2 domain / CH3 domain / CH2-CH3 region of a human IgG (e.g. hlgG 1 , hlgG2, hlgG3, hlgG4), hlgA (e.g. hlgA1 , hlgA2), h IgD , hlgE or hlgM. In some embodiments, the CH2 domain, CH3 domain and / or a CH2-CH3 region corresponds to the CH2 domain / CH3 domain / CH2-CH3 region of a human IgG 1 allotype (e.g. G1 ml , G1 m2, G1 m3 or G1 ml 7).In some embodiments, an antigen-binding molecule according to the present disclosure comprises one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:25. In some embodiments, the antigen-binding molecule comprises an Fc region comprising one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:25. In some embodiments, an antigenbinding molecule according to the present disclosure comprises one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:16 or 17.In some embodiments, the antigen-binding molecule comprises an Fc region comprising one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:16 or 17.Recombinant co-expression of constituent polypeptides of antigen-binding molecules and their subsequent association leads to several possible combinations. To improve the yield of the desired combinations of polypeptides in recombinant production, it is advantageous to introduce Fc region modification(s) promoting association of the desired combinations of polypeptides. Modifications may promote e.g. hydrophobic and / or electrostatic interaction between CH2 and / or CH3 regions of different polypeptide chains. Such modifications are described e.g. in Ha et al., Front Immunol. (2016) 7:394, which is hereby incorporated by reference in its entirety.In some embodiments, an antigen-binding molecule of the present disclosure comprises an Fc region comprising paired substitutions in the CH3 regions of the Fc region according to one of the following formats, as shown in Table 1 of Ha et al., Front. Immnol (2016) 7:394: KiH, KiHs s, HA-TF, ZW1 , 7.8.60, DD-KK, EW-RVT, EW-RVTs-s, SEED or A107.In some embodiments, an Fc region according to the present disclosure comprises the ‘knob-into-hole’ or ‘KiH’ modification which is described e.g. in US 7,695,936, Atwell et al., J Mol Biol. (1997) 270(1 ):26-35 and Carter, J Immunol Meth. (2001) 248(1-2):7-15. In such embodiments, one of the CH3 regions of the Fc region comprises a ‘knob’ modification, and the other CH3 region comprises a ‘hole’ modification. The ‘knob’ and ‘hole’ modifications are positioned within the respective CH3 regions so that the ‘knob’ can be positioned in the ‘hole’ in order to promote heterodimerisation (and inhibit homodimerisation) of the polypeptides and / or stabilise heterodimers. Knobs are constructed by substituting amino acids having small chains with those having larger side chains (e.g. tyrosine or tryptophan). Holes are created by substituting amino acids having large side chains with those having smaller side chains (e.g. alanine or threonine). In some embodiments, one of the CH3 regions of an Fc region of the present disclosure comprises the substitution T366W, and the other CH3 region of the Fc region comprises the substitution Y407V (numbering of positions / substitutions in the Fc, CH2 and CH3 regions herein is according to the EU numbering system as described in Edelman et al., Proc Natl Acad Sci USA (1969) 63(1): 78-85). In some embodiments, one of the CH3 regions of the Fc region comprises the substitution T366W, and the other CH3 region comprises the substitutions T366S and L368A. In some embodiments, one of the CH3 regions of the Fc region comprises the substitution T366W, and the other CH3 region comprises the substitutions Y407V, T366S and L368A.Fc regions provide for interaction with Fc receptors and other molecules of the immune system to bring about functional effects. Fc-mediated effector functions are reviewed e.g. in Jefferis et al., Immunol Rev 1998 163:59-76 (hereby incorporated by reference in its entirety), and are brought about through Fc- mediated recruitment and activation of immune cells (e.g. macrophages, dendritic cells, neutrophils, basophils, eosinophils, platelets, mast cells, NK cells and T cells) through interaction between the Fcregion and Fc receptors expressed by the immune cells, recruitment of complement pathway components through binding of the Fc region to complement protein C1 q, and consequent activation of the complement cascade. Fc-mediated functions include Fc receptor binding, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), complement-dependent cytotoxicity (GDC), formation of the membrane attack complex (MAC), cell degranulation, cytokine and / or chemokine production, and antigen processing and presentation.Modifications to antibody Fc regions that influence Fc-mediated functions are known in the art, such as those described e.g. in Wang et al., Protein Cell (2018) 9(1 ):63-73, which is hereby incorporated by reference in its entirety. Exemplary Fc region modifications known to influence antibody effector function are summarised in Table 1 of Wang et al., Protein Cell (2018) 9(1):63-73. In some embodiments, the antigen-binding moiety of the present disclosure comprises an Fc region comprising modification to increase or reduce an Fc-mediated function as compared to an antigen-binding moiety comprising the corresponding unmodified Fc region. Where an Fc region / CH2 / CH3 is described as comprising modification(s) ‘corresponding to’ reference substitution(s), equivalent substitution(s) in the homologous Fc / CH2 / CH3 are contemplated.In some embodiments, the antigen-binding molecule of the present disclosure comprises an Fc region comprising modification. In some embodiments, the antigen-binding molecule of the present disclosure comprises an Fc region comprising modification in one or more of the CH2 and / or CH3 regions.In some embodiments, the Fc region comprises modification to reduce / prevent an Fc-mediated function (e.g. ADCC, ADCP, CDC). In some embodiments, the Fc region comprises modification to reduce / prevent ADCC. In some embodiments, the Fc region comprises modification to reduce / prevent CDC. In some embodiments, the Fc region comprises modification to reduce / prevent binding to an Fc receptor. In some embodiments, the Fc region comprises modification to reduce / prevent binding to an Fey receptor. In some embodiments the Fc region comprises modification to reduce / prevent binding to one or more of FcyRI, FcyRlla, FcyRllb, FcyRllc, FcyRllla and FcyRlllb. In some embodiments the Fc region comprises modification to reduce / prevent binding to FcyRllla. In some embodiments the Fc region comprises modification to reduce / prevent binding to FcyRlla. In some embodiments the Fc region comprises modification to reduce / prevent binding to FcyRllb. In some embodiments the Fc region comprises modification to reduce / prevent binding to a complement protein. In some embodiments the Fc region comprises modification to reduce / prevent binding to C1q.WO 2017 / 137830 A1 discloses anti-VISTA antibody VSTB174, which is disclosed at e.g. paragraph

[0221] to comprise the variable regions of anti-VISTA antibody VSTB112. Paragraph

[0362] discloses that VSTB123 comprises the variable regions of VSTB174. Example 25 of WO 2017 / 137830 A1 at paragraph

[0417] and Figure 42A disclose that mlgG2a antibody VSTB123 was able to inhibit tumor growth in a MB49 tumor model. Paragraph

[0418] and Figure 42A disclose that by contrast VSTB124 - which is the same antibody provided in lgG2a LALA format; see paragraph

[0408] - did not inhibit tumor growth. Based on these results Example 25 concludes at paragraph

[0419] that efficacy with anti-VISTA antibody treatment might require active Fc. Accordingly, the proposed mechanism of action for the anti-VISTA antibody represented schematically at Figure 47 (see the legend to Figure 47 at paragraph

[0053] ) involves Fc-mediated engagement of FcyRIII expressed by NK cells.Hamster monoclonal anti-VISTA antibody mAb13F3 is disclosed in Le Mercier et al. Cancer Res. (2014) 74(7):1933-44 to inhibit tumor growth in B16OVA and B16-BL6 melanoma models. Page 1942, paragraph spanning left and right columns teaches that immunogenicity and the FcR binding activity of the VISTA mAb might be critical limiting factors for achieving optimal target neutralization and therapeutic efficacy.In some embodiments, the Fc region of antigen binding molecules and articles described herein comprises modification at the amino acid residue corresponding to N297. In some embodiments, the Fc region comprises modification corresponding to N297A or N297Q or N297G as described in Leabman et al., Mabs. (2013) 5:896-903. Substitution of ‘N297’ with ‘A’, ‘G’ or ‘Q’ is known to eliminate glycosylation, and thereby reduce Fc binding to C1q and Fey receptors, and thus also reducing CDC and ADCC. In some embodiments, the Fc region comprises modification corresponding to N297A.In some embodiments, an antigen-binding molecule according to the present disclosure comprises one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:39. In some embodiments, the antigen-binding molecule comprises an Fc region comprising one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:39. In some embodiments, an antigenbinding molecule according to the present disclosure comprises one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:37 or 38. In some embodiments, the antigen-binding molecule comprises an Fc region comprising one or more (e.g. two) polypeptides comprising an amino acid sequence having at least 60% amino acid sequence identity, e.g. one of >70%, >75%, >80%, >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94%, >95%, >96%, >97%, >98%, >99% or 100% amino acid sequence identity to the amino acid sequence of SEQ ID NO:37 or 38.In some embodiments the Fc region comprises modification corresponding to N297A or N297Q or N297G as described in Leabman et al., MAbs. (2013) 5:896-903. In some embodiments the Fc region comprises modification corresponding to L235E as described in Alegre et al., J Immunol. (1992) 148:3461-3468. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions L234A / L235A or F234A / L235A as described in Xu et al., Cell Immunol. (2000) 200:16-26. In some embodiments the Fc region comprises modification corresponding to P329A or P329G as described in Schlothauer et al., Protein Engineering, Design and Selection (2016), 29(10):457-466. In some embodiments the Fc region comprises modification corresponding to the combination ofsubstitutions L234A / L235A / P329G as described in Lo et al. J. Biol. Chem (2017) 292(9):3900-3908. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions described in Rother et al., Nat Biotechnol. (2007) 25:1256-1264. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions S228P / L235E as described in Newman et al., Clin. Immunol. (2001) 98:164-174. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions H268Q / V309L / A330S / P331S as described in An et al., MAbs. (2009) 1 :572-579. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions V234A / G237A / P238S / H268AA / 309L / A330S / P331S as described in Vafa et al., Methods. (2014) 65:114- 126. In some embodiments the Fc region comprises modification corresponding to the combination of substitutions L234A / L235E / G237A / A330S / P331S as described in US 2015 / 0044231 A1.The combination of substitutions “L234A / L235A” and corresponding substitutions (such as e.g. F234A / L235A in human lgG4) are known to disrupt binding of Fc to Fey receptors and inhibit ADCC, ADCP, and also to reduce C1q binding and thus CDC (Schlothauer et al., Protein Engineering, Design and Selection (2016), 29(10):457-466, hereby incorporated by reference in entirety). The substitutions “P329G” and “P329A” reduce C1 q binding (and thereby CDC). In some embodiments the Fc region comprises modification corresponding to the combination of substitutions L234A / L235A / P329G (LALA- PG) (residues A117, A118 and G212 in SEQ ID NO:78).In some embodiments the Fc region comprises modification corresponding to the combination of substitutions L234A / L235A / P329A (LALA-PA). This combination of substitutions is set out in SEQ ID NO:78 (human lgG1 heavy chain). These substitutions are equivalent to positions 117, 118 and 212, respectively, in SEQ ID NO:78. In some embodiments, an antigen binding molecule described herein comprises a heavy chain comprising an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:78. In some embodiments, an antigen binding molecule described herein comprises a heavy chain comprising an amino acid sequence having at least 70%, preferably one of 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity to SEQ ID NO:78 and comprises the combination of substitutions L234A / L235A / P329A (LALA- PA) (i.e. residues A117, A118 and A212 in SEQ ID NO:78). Heavy chain sequences for the antigen binding molecules described herein containing the LALA-PA modifications are disclosed herein, see e.g. Table D.Linker-payload moietiesThe antigen-binding molecules described herein may be used as portions of antibody-drug conjugates (ADCs). That is, the present disclosure provides antibody-drug conjugates (ADCs) that comprise the antigen-binding molecules described herein. The antigen-binding molecules described herein may comprise a linker-payload moiety. As used herein, a linker-payload moiety refers to a moiety comprising a payload moiety, and a linker moiety for linking the payload moiety to the antigen-binding region of the antigen-binding molecule of the present disclosure.A payload moiety according to the present disclosure may comprise or consist of a cytotoxic agent. Payload moieties are described e.g. in Parslow et al., Biomedicines. 2016 Sep; 4(3): 14, Goundry and Parker, Org. Process Res. Dev. (2022) 26, 8, 2121-2123, Fu et al., Signal Transduction and Targeted Therapy (2022) 7:93, Wang et al., Acta Pharmaceutica Sinica B (2023) 13 (10): 4025-4059 and Conilh et al., J. Hematol. & Oncol. (2023) 16:3, all of which are hereby incorporated by reference in their entirety.In some embodiments, a payload moiety according to the present disclosure may comprise or consist of a microtubule-targeting agent, a DNA-targeting agent, an RNA-targeting agent, an immune systemactivating agent, an apoptosis-promoting agent, a metabolism-inhibiting agent and a proteasome inhibiting agent.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a microtubule-targeting agent. Microtubules play important roles in maintaining proper cellular morphology, signal transduction, organelle transportation, cell motility and cell division. Microtubules are formed of tubulin, and agents that disrupt the tubulin polymerization dynamics, resulting in cell cycle arrest and apoptosis. Tubulin inhibitors have a stronger toxicity to rapidly-dividing cancerous cells than slower- growing, non-cancerous cells. Microtubule-targeting agents include tubulin polymerization enhancers (e.g. auristatins, taxanes), and tubulin polymerization inhibitors (e.g. maytansinoids, colchicine). In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a maytansinoid, e.g. maytansine or a derivative thereof, e.g. mytansine, DM1 (mertansine) or DM4 (ravtansine). In some embodiments, a payload moiety comprises, or consists of colchicine or a derivative thereof. In some embodiments, a payload moiety comprises, or consists of, an auristatin, e.g. a dolastatin 10 derivative, e.g. monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), auristatin PE, auristatin PYE, PF-06380101 , auristatin F-hydroxypropylamide (AF-HPA) or azastatin. In some embodiments, a payload moiety comprises, or consists of, a halichondrin B derivative, e.g. eribulin. In some embodiments, a payload moiety comprises, or consists of, a tubulysin or a derivative thereof, e.g. tubulysin A, D, H, U or V. In some embodiments, a payload moiety comprises, or consists of, a cryptophycin or a derivative thereof, e.g. cryptophycin-1 , cryptophycin-52, cryptophycin-55 or cryptophycin-55gly. In some embodiments, a payload moiety comprises, or consists of, an EG5 (i.e. kinesin / KSP / KIF11) inhibitor, e.g. ispinesib (SB715992) or a derivative thereof, or filanesib (ARRY-520) or a derivative thereof. In some embodiments, a payload moiety comprises, or consists of, a taxane, e.g. paclitaxel, docetaxel or cabazitaxel. In some embodiments, a payload moiety comprises, or consists of vinca alkaloid, e.g. vinblastine, vincristine, vindesine, vinorelbine or vinflunine. In some embodiments, a payload moiety comprises, or consists of hemiasterlin or a derivative thereof, e.g. hemiasterlin, hemisterlin A or HTI-286.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a DNA-targeting agent. DNA-targeting agents include agents that directly or indirectly destroy DNA through introducing / promoting the formation of single- and / or double-strand breaks (e.g. enediynes, topoisomerase inhibitors), DNA alkylating agents (e.g. pyrrolo[2,1-c][1 ,4] benzodiazepines, indolinobenzodiazpines, duocarmycins), and DNA crosslinking agents (e.g. mitomycin C). In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, anenediyne, e.g. a Gal-like enediyne or an anthraquinone fusion enediyne, e.g. calciheamicin y'-i , calciheamicin 0'i or uncialamycin. In some embodiments, a payload moiety comprises, or consists of, a topoisomerase inhibitor, e.g. a TOP1 or TOP2 inhibitor, e.g. camptothecin or a derivative thereof, e.g. SN- 38, exatecan, exatecan mesylate (DX-8951f), A / -glycyl-exatecan or Dxd; e.g. an anthracycline, e.g. doxorubicin, daunorubicin, epirubicin, PNU-159682 or idarubicin. In some embodiments, a payload moiety comprises, or consists of, a pyrrolo[2,1-c][1 ,4] benzodiazepine (PBD) dimer, or a derivative thereof, e.g. a PDB, KMR-28-39, SJG-136 SGD-1882 or SG3199 dimer. In some embodiments, a payload moiety comprises, or consists of, indolinobenzodiazpine (IGN; monoimine) or a derivative thereof. In some embodiments, a payload moiety comprises, or consists of, a pyridinobenzodiazepine (PDD) dimer, or a derivative thereof, e.g. a PDD or FGX5-67 dimer. In some embodiments, a payload moiety comprises, or consists of, a duocarmycin or a derivative thereof, e.g. duocarmycin A, CC1065, duocarmycin SA, DUBA, seco-DIBA or seco-CBI. In some embodiments, a payload moiety comprises, or consists of, mitomycin C.In some embodiments, a payload moiety comprises or consists of exatecan:In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a RNA-targeting agent. Small molecule inhibitors that target RNA can kill both dividing and dormant tumor cells. RNA-targeting agents include RNA splicing inhibitors (e.g. thailanstatin and derivatives thereof) and RNA polymerase II inhibitors (e.g. amatoxins, RNA polymerase ll-IN-2). In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, thailanstatin or a derivative thereof, e.g. thailanstatin A, thailanstatin B, thailanstatin C or FR901464. In some embodiments, a payload moiety comprises, or consists of, an amatoxin, e.g. a-amanitin or 0-amanitin. In some embodiments, a payload moiety comprises, or consists of, RNA polymerase ll-IN-2.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, an immune system-activating agent. Immune-stimulating antibody conjugates (ISACs) employ small molecule-based engagement of the innate and / or adaptive immune systems. A variety of immune- modulating payloads are in development, including Toll-like receptor (TLR) agonists, stimulator of interferon genes (STING) agonists and glucocorticoid receptor modulators (GRMs). In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a TLR agonist, e.g. an agonist of TLR7, TLR8 or TLR9. In some embodiments, a payload moiety comprises, or consists of, a STING agonist, e.g. a cyclic dinucleotide (CDN; e.g. 2,3 cGAMP; 3,3 cGAMP; c-di-GMP orc-di-AMP) or a benzimidazole. In some embodiments, a payload moiety comprises, or consists of, a glucocorticoid receptor modulator, e.g. dexamethasone or a derivative thereof.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, an apoptosis-promoting agent. Anti-apoptotic proteins such as Bcl-xL can play important roles in tumorigenesis, metastasis and drug resistance. In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a Bcl-xL inhibitor. In some embodiments, a payload moiety comprises, or consists of, ABT-737.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a metabolism-inhibiting agent. Metabolism-inhibiting agents such as niacinamide phosphate ribose transferase (NAMPT) inhibitors control the concentration of NAD+ within cells, inducing energy crisis and cell death, and antifolate antimetabolites such as methotrexate, that inhibit dihydrofolate reductase (DHFR) and thereby DNA synthesis. In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a NAMPT inhibitor, e.g. FK-866 or A-1293201 . In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a DHFR inhibitor, e.g. methotrexate of a derivative thereof.In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a proteasome-inhibiting agent. Proteasome-inhibiting agents include carmaphycins. In some embodiments, a payload moiety according to the present disclosure comprises, or consists of, a carmaphycin or a derivative thereof, e.g. carmaphycin A or carmaphycin B.A linker moiety according to the present disclosure may be any moiety suitable for linking the payload moiety to the antigen-binding region of the antigen-binding molecule of the present disclosure.Accordingly, they generally comprise a group enabling connection to the payload moiety, a group connecting conjugation to the antigen-binding region of the antigen-binding molecule, and a linker core.Linker moieties are described e.g. in Su et al., Acta Pharmaceutica Sinica B (2021) 11 (12): 3889-3907, and Fu et al., Signal Transduction and Targeted Therapy (2022) 7:93.A linker moiety according to the present disclosure may be a cleavable linker moiety or a non-cleavable moiety.Cleavable linkers typically utilise differences between the environment of systemic circulation and that in cancer cells / the tumor microenvironment to release the payload moiety in a targeted manner. Cleavable linkers include chemical cleavage linkers (e.g. acid-cleavable linkers, GSH-cleavable linkers, Fe(ll)- cleavable linkers) and enzyme cleavage linkers (e.g. cathepsin-cleavable linkers, glycosidase-cleavable linkers, phosphatase-cleavable linkers, sulfatase-cleavable linkers).In some embodiments, a linker moiety according to the present disclosure is a chemical cleavage linker. In some embodiments, a linker moiety according to the present disclosure is an enzyme cleavage linker.In some embodiments, a linker moiety is an acid-cleavable linker, e.g. comprising a hydrazone group (e.g. a 6-maleimidocaproylhydrazone linker or a (4-(4-acetylphenoxy)butanoic acid) hydrazaone linker), a carbonate group or a silyl ether group. In some embodiments, a linker moiety is a GSH-cleavable linker, e.g. comprising a disulfide group. In some embodiments, a linker moiety is a Fe(ll)-cleavable linker, e.g. comprising a 1 ,2,4-trioxolane group. In some embodiments, a linker moiety is a cathepsin-cleavable linker, e.g. comprising a dipeptide (e.g. a valine-citrulline linker, a phenylalanine-lysine linker or a valinealanine linker), a triglycyl peptide (CX) or a cBu-Cit group. In some embodiments, a linker moiety is a glucuronidase-cleavable linker, e.g. comprising a 0-glucuronide group. In some embodiments, a linker moiety is a glycosidase-cleavable linker, e.g. comprising a 0-galactoside group. In some embodiments, a linker moiety is a phosphatase-cleavable linker, e.g. comprising a pyrophosphate group. In some embodiments, a linker moiety is a sulfatase-cleavable linker, e.g. comprising an arylsulfate group. In some embodiments, a linker moiety is a photo-responsive linker, e.g. comprising a heptamethine cyanine fluorophore group, an O-nitrobenzyl group or a PC4AP group. In some embodiments, a linker moiety is a biorthogonal cleavable linker, e.g. comprising a dsProc group.Non-cleavable linkers remain inert in common chemical and enzymatic environments in the body, with the payload moiety being released following processing of the ADC by cellular lysosomal proteases. Non- cleavable linkers include linkers comprising thioether or maleimidocaproyl groups.In some embodiments, a linker moiety is a thioether linker. In some embodiments, a linker moiety is a maleimidocaproyl linker, e.g. comprising a 2-(maleimidomethyl)-1 ,3-dioxane (MD) group or a Mal-PAB group. In some embodiments, a linker moiety comprises a polyethylene glycol (PEG) group and an alkyne, triazole or piperazine group.In some embodiments, a linker-payload moiety according to the present disclosure has an amino (-NH2) group for linkage to the antigen-binding moiety, for example by enzymatic conjugation. In some of these embodiments, enzymatic conjugation with microbial transglutaminase may be used to conjugate the linker-payload moiety to the antigen-binding moiety.In some embodiments, a linker moiety further comprises a spacer moiety. Spacer moieties are sometimes required due to the bulky nature of payload moieties. Commonly employed spacer moieties include paraaminobenzyl carbamate (PABC), hemiaminal groups, PEG groups, polar acyl sulfamide groups, a polar carbamoyl sulfamide groups and HydraSpace (described e.g. in Verkade et al., Antibodies (Basel) (2018) 7(1 ):12 and WO 2016 / 053107 A1 , both of which are hereby incorporated by reference in their entirety). PABC is commonly employed as a spacer moiety in cathepsin-cleavable dipeptide linkers, 0- glucuronidase-cleavable linkers and, p-galactosidase-cleavable linkers and phosphatase cleavable linkers.In some embodiments, a linker-payload moiety according to the present disclosure comprises, or consists of, ozogamicin, vedotin, emtansine, deruxtecan, govitecan, mafodotin, tesirine or soravtansine. The structures of the linker-payload moieties referred to in the preceding sentence are shown e.g. in Lim et al., Drugs Drug Candidates (2023) 2(2), 377-421 , which is hereby incorporated by reference in its entirety (see in particular Figure 4).Functional properties of the antigen-binding moleculesThe antigen-binding molecules described herein may be characterised by reference to certain functional properties. In some embodiments, an antigen-binding molecule described herein may possess one or more of the following properties: binds to VISTA (e.g. human, rhesus and / or cynomolgus macague VISTA); does not bind to mouse VISTA; does not bind to rat VISTA; binds to cells expressing VISTA; inhibits interaction between VISTA and an interaction partner for VISTA (e.g. LRIG1 , PSGL-1 , or VSIG3) inhibits VISTA- mediated signalling; inhibits proliferation of cells expressing VISTA; increases killing of cells expressing VISTA; reduces the number / proportion of VISTA-expressing cells; inhibits tumor growth and / or reduces tumor size / volume (e.g. of a VISTA-expressing cancer); increases survival of subjects having a cancer (e.g. a VISTA-expressing cancer).It will be appreciated that a given antigen-binding molecule may display more than one of the properties recited in the preceding paragraph. A given antigen-binding molecule may be evaluated for the properties recited in the preceding paragraph using suitable assays. For example, the assays may be e.g. in vitro assays, optionally cell-based assays or cell-free assays. In some embodiments, the assays may be e.g. in vivo assays, i.e. performed in non-human animals. In some embodiments, the assays may be e.g. ex vivo assays, i.e. performed using cells / tissue / an organ obtained from a subject.Where assays are cell-based assays, they may comprise treating cells with an antigen-binding molecule in order to determine whether the antigen-binding molecule displays one or more of the recited properties. Assays may employ species labelled with detectable entities in order to facilitate their detection. Assays may comprise evaluating the recited properties following treatment of cells separately with a range of quantities / concentrations of a given antigen-binding molecule (e.g. a dilution series).Analysis of the results of such assays may comprise determining the concentration at which 50% of the maximal level of the relevant activity is attained. The concentration of a given agent at which 50% of the maximal level of the relevant activity is attained may be referred to as the ‘half-maximal effective concentration’ of the agent in relation to the relevant activity, which may also be referred to as the ‘EC50’. Depending on the property, the EC50 may also be referred to as the ‘half-maximal inhibitory concentration’ or ‘IC50’, this being the concentration of the agent at which 50% of the maximal level of inhibition of a given property is observed. By way of illustration, the IC50 of a given antigen-binding molecule for inhibiting interaction between VISTA and an interaction partner for VISTA (e.g. LRIG1 , PSGL-1 or VSIG3) may be the concentration at which 50% of the maximal level of inhibition is achieved.The antigen-binding molecules described herein bind to VISTA. In preferred embodiments, the antigenbinding molecules display specific binding to VISTA. As used herein, “specific binding” refers to binding which is selective for the antigen, and which can be discriminated from non-specific binding to non-target antigen. An antigen-binding molecule that specifically binds to VISTA preferably binds to VISTA with greater affinity, and / or with greater duration than it binds to other, non-target molecules.The ability of a given polypeptide to bind specifically to a given molecule can be determined by analysis according to methods known in the art, such as by ELISA, Surface Plasmon Resonance (SPR; see e.g. Hearty et al., Methods Mol Biol (2012) 907:411-442), Bio-Layer Interferometry (see e.g. Lad et al., (2015) J Biomol Screen 20(4): 498-507), flow cytometry, or by a radiolabeled antigen-binding assay (RIA) enzyme-linked immunosorbent assay. Through such analysis binding to a given molecule can be measured and quantified. In some embodiments, the binding may be the response detected in a given assay.In some embodiments, the extent of binding of the antigen-binding molecule to an non-target molecule is less than about 10% of the binding of the antibody to the target molecule as measured, e.g. by ELISA, SPR, Bio-Layer Interferometry or by RIA. Alternatively, binding specificity may be reflected in terms of binding affinity where the antigen-binding molecule binds with a dissociation constant (KD) that is at least 0.1 order of magnitude ( / .e. 0.1 x 10n, where n is an integer representing the order of magnitude) greater than the KD of the antigen-binding molecule towards a non-target molecule. This may optionally be one of at least 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1 .0, 1 .5, or 2.0.In some embodiments, an antigen-binding molecule according to the present disclosure binds to VISTA with an affinity in the micromolar range, i.e. KD = 9.9 x 10-4to 1 x 10-6M. In some embodiments, an antigen-binding molecule binds to VISTA with sub-micromolar affinity, i.e. KD < 1 x 10-6M. In some embodiments, an antigen-binding molecule binds to VISTA with an affinity in the nanomolar range, i.e. KD = 9.9 x 10 '" to 1 x IO9M. In some embodiments, an antigen-binding molecule binds to VISTA with sub- nanomolar affinity, i.e. KD < 1 x 109M. In some embodiments, an antigen-binding molecule binds to VISTA with an affinity in the picomolar range, i.e. KD = 9.9 x 1010to 1 x 1012M. In some embodiments, an antigen-binding molecule binds to VISTA with sub-picomolar affinity, i.e. KD < 1 x 1012M.In some embodiments, an antigen-binding molecule according to the present disclosure binds to VISTA with a KD of 10 pM or less, preferably one of <5 pM, <2 pM, <1 pM, <500 nM, <100 nM, <75 nM, <50 nM, <40 nM, <30 nM, <20 nM, <15 nM, <12.5 nM, <10 nM, <9 nM, <8 nM, <7 nM, <6 nM, <5 nM, <4 nM <3 nM, <2 nM, <1 nM, <500 pM, <400 pM, <300 pM, <200 pM, <100 pM, <50 pM, <40 pM, <30 pM, <20 pM, <10 pM or <1 pM. In some embodiments, an antigen-binding molecule according to the present disclosure binds to VISTA with a KD (e.g. as determined by SPR (Biocore) analysis, e.g. SPR analysis as described in the Examples of the present disclosure) of <1 nM (e.g. one of <900 pM, <800 pM, <700 pM, <600 pM, <500 pM, <400 pM, <300 pM).In some embodiments, an antigen-binding molecule according to the present disclosure binds to human VISTA with a KD (e.g. as determined by SPR (Biocore) analysis) of <1 nM (e.g. one of <900 pM, <800 pM,<700 pM, <600 pM, <500 pM). In some embodiments, an antigen-binding molecule according to the present disclosure binds to cynomolgus macaque VISTA with a KD (e.g. as determined by SPR (Biocore) analysis) of <1 nM (e.g. one of <900 pM, <800 pM, <700 pM, <600 pM, <500 pM, <400 pM). In some embodiments, an antigen-binding molecule according to the present disclosure binds to rhesus macaque VISTA with a KD (e.g. as determined by SPR (Biocore) analysis) of <1 nM (e.g. one of <900 pM, <800 pM, <700 pM, <600 pM, <500 pM, <400 pM).In some embodiments, an antigen-binding molecule according to the present disclosure binds to VISTA with an ECso (e.g. as determined by ELISA, e.g. an ELISA as described in the Examples of the present disclosure) of 1 pM or less, e.g. one of <500 nM, <100 nM, <50 nM, <40 nM, <30 nM, <20 nM, <10 nM, <5 nM, <4 nM <3 nM, <2 nM, <1 nM, <500 pM, <400 pM, <300 pM, <200 pM, <100 pM, <50 pM, <40 pM, <30 pM, <20 pM, <15 pM, <10 pM, <5 pM or <1 pM.In some embodiments, the antigen-binding molecule displays binding to human VISTA, rhesus macaque VISTA (Macaca mulatta), and / or cynomolgus macaque (Macaca fascicularis) VISTA. In some embodiments, the antigen-binding molecule does not to bind murine (e.g. mouse) VISTA and / or does not bind to rat VISTA. In some embodiments, the antigen-binding molecule binds to human VISTA and rhesus VISTA and cynomolgus macaque VISTA. In some embodiments, the antigen-binding molecule binds to human VISTA and rhesus VISTA and cynomolgus macaque VISTA, and does not bind to rat VISTA and murine (e.g. mouse) VISTA. In some embodiments, the antigen-binding molecule is cross- reactive for human VISTA and rhesus VISTA and cynomolgus macaque VISTA. In some embodiments, the antigen-binding molecule of the present disclosure displays cross-reactivity with VISTA of a nonhuman primate. Cross-reactivity to VISTA in model species allows in vivo exploration of efficacy in syngeneic models without relying on surrogate molecules.In some embodiments, an antigen-binding molecule according to the present disclosure binds to human VISTA with an ECso (e.g. as determined by ELISA, e.g. an ELISA as described in the Examples of the present disclosure) of <50 pM (e.g. one of <25 pM, <20 pM, <15 pM, <10 pM). In some embodiments, an antigen-binding molecule according to the present disclosure binds to cynomolgus macaque VISTA with an ECso (e.g. as determined by ELISA, e.g. an ELISA as described in the Examples of the present disclosure) of <60 pM (e.g. one of <55 pM, <50 pM, <45 pM). In some embodiments, an antigen-binding molecule according to the present disclosure binds to rhesus macaque VISTA with an EC50 (e.g. as determined by ELISA, e.g. an ELISA as described in the Examples of the present disclosure) of <70 pM (e.g. one of <65 pM, <60 pM, <55 pM, <50 pM, <40 pM).In some embodiments, an antigen-binding molecule according to the present disclosure binds to VISTA (e.g. human VISTA) with similar affinity at pH from 5.5 to pH 7.5. For example, in some embodiments, the antigen-binding molecule displays similar affinity for VISTA at pH 5.5 as the affinity for VISTA at pH 7.5.Herein, a binding affinity which is ‘similar’ to a reference binding affinity means a binding affinity which is within 50%, e.g. within one of 40%, 45%, 30%, 25%, 20% 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%,11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% of the reference binding affinity, as determined under comparable conditions.In some embodiments, the antigen-binding molecule of the present disclosure binds to VISTA in a region which is accessible to an antigen-binding molecule ( / .e., an extracellular antigen-binding molecule) when the relevant antigen is expressed at the cell surface ( / .e. in or at the cell membrane). In some embodiments, the antigen-binding molecule binds to VISTA expressed at the cell surface of a cell expressing the relevant antigen. In some embodiments, the antigen-binding molecule binds to VISTA- expressing cells.The ability of an antigen-binding molecule to bind to a given cell type can be analysed by contacting cells with the antigen-binding molecule, and detecting antigen-binding molecule bound to the cells, e.g. after a washing step to remove unbound antigen-binding molecule. The ability of an antigen-binding molecule to bind to cells expressing VISTA can be analysed by methods such as flow cytometry and immunofluorescence microscopy.In some embodiments, the antigen-binding molecule inhibits proliferation of cells expressing VISTA (e.g. cancer cells expressing VISTA). The ability of an antigen-binding molecule to inhibit proliferation of a given cell type can be analysed by contacting cells with the antigen-binding molecule, and subsequently evaluating proliferation of the cells (i.e. after a period of time sufficient for an effect on cell proliferation to be observed). Cell proliferation can be evaluated e.g. by detecting changes in number of cells over time, or by in vitro analysis of incorporation of3H-thymidine or by CFSE dilution assay, e.g. as described in Fulcher and Wong, Immunol Cell Biol (1999) 77(6): 559-564, hereby incorporated by reference in entirety.In some embodiments, the antigen-binding molecule of the present invention is capable of inhibiting proliferation of cells expressing VISTA to less than 1 times, e.g. <0.99 times, <0.95 times, <0.9 times, <0.85 times, <0.8 times, <0.75 times, <0.7 times, <0.65 times, <0.6 times, <0.55 times, <0.5 times, <0.45 times, <0.4 times, <0.35 times, <0.3 times, <0.25 times, <0.2 times, <0.15 times, <0.1 times, <0.05 times, or <0.01 times the level of proliferation of the same cells observed in the absence of the antigen-binding molecule (or in the presence of an appropriate control antigen-binding molecule known not to influence proliferation of cells expressing VISTA), in a given assay.In some embodiments, the antigen-binding molecule described herein inhibits proliferation of cells expressing VISTA with an IC50 of 100 nM or less, preferably one of <50 nM, <40 nM, <30 nM, <20 nM, <10 nM, <5 nM, <4 nM, <3 nM, <2 nM, <1 nM, <900 pM, <800 pM, <700 pM, <600 pM or <500 pM.In some embodiments, the antigen-binding molecule according to the present disclosure potentiates (i.e. upregulates, enhances) cell killing of cells comprising / expressing VISTA.In some embodiments, an antigen-binding molecule according to the present disclosure may inhibit growth or reduce metastasis of a cancer comprising cells comprising / expressing VISTA. In some embodiments, an antigen-binding molecule may potentiate (i.e. upregulate, enhance) cell killing of cellscomprising / expressing VISTA. In some embodiments, an antigen-binding molecule may inhibit growth of cells of a cancer, or may inhibit growth of a tumor, comprising cells comprising / expressing VISTA. In some embodiments, an antigen-binding molecule may inhibit metastasis of a cancer / tumor comprising cells comprising / expressing VISTA.Cell killing can be investigated, for example, using any of the methods reviewed in Zaritskaya et al., Expert Rev Vaccines (2011), 9(6):601 -616, hereby incorporated by reference in its entirety. Examples of in vitro assays of cytotoxicity / cell killing assays include release assays such as the51Cr release assay, the lactate dehydrogenase (LDH) release assay, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) release assay, ATP release assay using Cell Titre Gio, and the calcein-acetoxymethyl (calcein-AM) release assay. These assays measure cell killing based on the detection of factors released from lysed cells.In some embodiments an antigen-binding molecule according to the present disclosure is capable of reducing the number / proportion of cells expressing VISTA. In some embodiments, an antigen-binding molecule according to the present disclosure is capable of depleting / enhancing depletion of such cells.In some embodiments, an antigen-binding molecule of the present disclosure displays anticancer activity. In some embodiments, the antigen-binding molecule increases killing of cancer cells. In some embodiments, the antigen-binding molecule causes a reduction in the number of cancer cells in vivo, e.g. as compared to an appropriate control condition. The cancer may be a cancer as described herein, e.g. a cancer expressing / overexpressing VISTA.In some embodiments, an antigen-binding molecule according to the present disclosure reduces / inhibits growth of a cancer and / or of a tumor of a cancer. In some embodiments, an antigen-binding molecule reduces tissue invasion by cells of a cancer. In some embodiments, an antigen-binding molecule reduces metastasis of a cancer. In some embodiments, an antigen-binding molecule displays anticancer activity. In some embodiments, an antigen-binding molecule reduces the growth / proliferation of cancer cells. In some embodiments, an antigen-binding molecule reduces the survival of cancer cells. In some embodiments, an antigen-binding molecule increases the killing of cancer cells. In some embodiments, an antigen-binding molecule of the present disclosure causes a reduction in the number of cancer cells e.g. in vivo. The cancer may be a cancer comprising cells expressing VISTA.An antigen-binding molecule of the present disclosure may be analysed for the properties described in the preceding paragraph in appropriate assays. Such assays include e.g. in vivo models.In some embodiments, administration of an antigen-binding molecule according to the present disclosure may cause one or more of: inhibition of the development / progression of the cancer, a delay to / prevention of onset of the cancer, a reduction in / delay to / prevention of tumor growth, a reduction in / delay to / prevention of tissue invasion, a reduction in / delay to / prevention of metastasis, a reduction in the severity of one or more symptoms of the cancer, a reduction in the number of cancer cells, a reduction inthe cancer burden, a reduction in tumor size / volume, and / or an increase in survival of subjects having the cancer (e.g. progression free survival or overall survival), e.g. as determined in an appropriate model.It will be appreciated that the properties recited in the preceding paragraph are evaluated after a period of time sufficient for an effect associated with treatment using the antigen-binding molecule to be observed. Tumor growth may be monitored by investigating tumor volume over time. Tumor growth may be evaluated by measuring tumor volume (e.g. in mm3) over time.In some embodiments, an antigen-binding molecule of the present disclosure is capable of reducing tumor size / volume (e.g. the mean tumor size / volume for the treatment group in an in vivo model, e.g. of a VISTA-expressing cancer) to less than 1 times, e.g. <0.99 times, <0.95 times, <0.9 times, <0.85 times, <0.8 times, <0.75 times, <0.7 times, <0.65 times, <0.6 times, <0.55 times, <0.5 times, <0.45 times, <0.4 times, <0.35 times, <0.3 times, <0.25 times, <0.2 times, <0.15 times, <0.1 times, <0.05 times, or <0.01 times the tumor size / volume observed at the same time point in the absence of treatment with the antigen-binding molecule (or following treatment with an appropriate control antigen-binding molecule known not to influence tumor growth), in a given assay. In some embodiments, evaluation of tumor size / volume for the purposes of such comparison is performed after more than 5 days, e.g. one of >10 days, >15 days, >20 days, >25 days, >30 days, >35 days, >40 days, >45 days, >50 days, >55 days, >60 days, >65 days, >70 days, >75 days, >80 days, >85 days, >90 days, >95 days or >100 days following administration of the first dose of the antigen-binding molecule, in the relevant model.In some embodiments, an antigen-binding molecule of the present disclosure achieves a level of tumor growth inhibition (e.g. expressed as % tumor growth inhibition, e.g. calculated relative to tumor growth observed on treatment with an appropriate control antigen-binding molecule) which is greater than 1 times, e.g. one of >1 .01 times, >1 .02 times, >1 .03 times, >1 .04 times, >1 .05 times, >1.1 times, >1 .2 times, >1 .3 times, >1 .4 times, >1 .5 times, >1 .6 times, >1 .7 times, >1 .8 times, >1 .9 times, >2 times, >3 times, >4 times, >5 times, >6 times, >7 times, >8 times, >9 times or >10 times the level of tumor growth inhibition observed at the same time point in the absence of treatment with the antigen-binding molecule (or following treatment with an appropriate control antigen-binding molecule known not to influence tumor growth), in a given assay. In some embodiments, evaluation of tumor growth inhibition for the purposes of such comparison is performed after more than 5 days, e.g. one of >10 days, >15 days, >20 days, >25 days, >30 days, >35 days, >40 days, >45 days, >50 days, >55 days, >60 days, >65 days, >70 days, >75 days, >80 days, >85 days, >90 days, >95 days or >100 days following administration of the first dose of the antigen-binding molecule, in the relevant model.In some embodiments, an antigen-binding molecule of the present disclosure is capable of increasing median survival of subjects having a cancer (e.g. in an in vivo model, e.g. of a VISTA-expressing cancer) to greater than 1 times, e.g. one of >1 .01 times, >1 .02 times, >1 .03 times, >1 .04 times, >1 .05 times, >1 .1 times, >1 .2 times, >1 .3 times, >1 .4 times, >1 .5 times, >1 .6 times, >1 .7 times, >1 .8 times, >1 .9 times, >2 times, >3 times, >4 times, >5 times, >6 times, >7 times, >8 times, >9 times or >10 times the median survival observed in the absence of treatment with the antigen-binding molecule (or following treatment with an appropriate control antigen-binding molecule known not to influence survival of subjects havingthe cancer), in a given assay. Median survival may be expressed in days from the start of the experiment, for subjects in the relevant treatment groups.Additional sequencesThe antigen-binding molecules of the present disclosure and their constituent polypeptides may additionally comprise further amino acids or sequences of amino acids.The polypeptides of the present disclosure may comprise one or more linker sequences between sequences of amino acids. Linker sequences are known to the skilled person, and are described, for example in Chen et al., Adv Drug Deliv Rev (2013) 65(10): 1357-1369, which is hereby incorporated by reference in its entirety. In some embodiments, a linker sequence may be a flexible linker sequence. Flexible linker sequences allow for relative movement of the amino acid sequences which are linked by the linker sequence. Flexible linkers are known to the skilled person, and several are identified in Chen et al., Adv Drug Deliv Rev (2013) 65(10): 1357-1369. Flexible linker sequences often comprise high proportions of glycine and / or serine residues.In some embodiments, the linker sequence comprises at least one glycine residue and / or at least one serine residue. In some embodiments, the linker sequence comprises or consists of glycine and serine residues. In some embodiments, the linker sequence has the structure: (GxS)n or (GxS)nGm; wherein G = glycine, S = serine, x = 3 or 4, n = 2, 3, 4, 5 or 6, and m = 0, 1 , 2 or 3. In some embodiments, the linker sequence comprises one or more (e.g. 1 , 2, 3, 4, 5 or 6) copies (e.g. in tandem) of the sequence motif G4S. In some embodiments, the linker sequence comprises or consists of (648)4 or (G4S)e. In some embodiments, the linker sequence has a length of 1 -2, 1-3, 1-4, 1-5, 1-10, 1-15, 1 -20, 1 -25, or 1 -30 amino acids.The antigen-binding molecules of the present disclosure and their constituent polypeptides may comprise amino acid sequence(s) to facilitate expression, folding, trafficking, processing, purification or detection of the antigen-binding molecule / polypeptide. For example, antigen-binding molecules and polypeptides of the present disclosure may additionally comprise a sequence of amino acids forming a detectable moiety, e.g. as described hereinbelow.The antigen-binding molecules of the present disclosure and their constituent polypeptides may additionally comprise a signal peptide (also known as a leader sequence or signal sequence). Signal peptides normally consist of a sequence of 5-30 hydrophobic amino acids, which form a single alpha helix. Secreted proteins and proteins expressed at the cell surface often comprise signal peptides. Signal peptides are known for many proteins, and are recorded in databases such as GenBank, UniProt and Ensembl, and / or can be identified / predicted e.g. using amino acid sequence analysis tools such as SignalP (Petersen et al., 2011 Nature Methods 8: 785-786) or Signal-BLAST (Frank and Sippl, 2008 Bioinformatics 24: 2172-2176).The signal peptide may be present at the N-terminus of the polypeptide, and may be present in the newly synthesised polypeptide. The signal peptide provides for efficient trafficking of the polypeptide. Signal peptides are often removed by cleavage, and thus are not comprised in the mature polypeptide.Signal peptides are known for many proteins, and are recorded in databases such as GenBank, UniProt, Swiss-Prot, TrEMBL, Protein Information Resource, Protein Data Bank, Ensembl, and InterPro, and / or can be identified / predicted e.g. using amino acid sequence analysis tools such as SignalP (Petersen et al., 2011 Nature Methods 8: 785-786) or Signal-BLAST (Frank and Sippl, 2008 Bioinformatics 24: 2172- 2176).Labels and conjugatesIn some embodiments, the antigen-binding molecules of the present disclosure and their constituent polypeptides comprise a detectable moiety.In some embodiments, a detectable moiety is a fluorescent label, phosphorescent label, luminescent label, immuno-detectable label (e.g. an epitope tag), radiolabel, chemical, nucleic acid or enzymatic label. An antigen-binding molecule or a constituent polypeptide thereof may be covalently or non-covalently labelled with the detectable moiety.Fluorescent labels include e.g. fluorescein, rhodamine, allophycocyanin, eosine and NDB, green fluorescent protein (GFP), chelates of rare earths such as europium (Eu), terbium (Tb) and samarium (Sm), tetramethyl rhodamine, Texas Red, 4-methyl umbelliferone, 7-amino-4-methyl coumarin, Cy3, and Cy5. Radiolabels include radioisotopes such as Hydrogen3, Sulfur35, Carbon14, Phosphorus32, Iodine123, Iodine125, Iodine126, Iodine131, Iodine133, Bromine77, Technetiurn99m, Indium111, lndiurn113m, Gallium67, Gallium68, Ruthenium95, Ruthenium97, Ruthenium103, Ruthenium105, Mercury207, Mercury203, Rheniurn99m, Rhenium101, Rhenium105, Scandium47, Telluriurn121 m, Telluriurn122m, Telluriurn125m, Thulium165, Thuliuml167, Thulium168, Copper67, Fluorine18, Yttrium90, Palladium100, Bismuth217and Antimony211. Luminescent labels include as radioluminescent, chemiluminescent (e.g. acridinium ester, luminol, isoluminol) and bioluminescent labels. Immuno-detectable labels include haptens, peptides / polypeptides, antibodies, receptors and ligands such as biotin, avidin, streptavidin or digoxigenin. Nucleic acid labels include aptamers.In some embodiments, an antigen-binding molecule or a constituent polypeptide thereof comprises a radionuclide. Such conjugates may be called radionuclide drug conjugates (RDCs) or radioimmunoconjugates (RICs). In some embodiments, an antigen-binding molecule or a constituent polypeptide thereof comprises a chelator group that is capable of chelating a radionuclide. Radionuclides include radioisotopes such as those listed above, or others such as Lutetium177, Actinium225and Strontium90.In some embodiments, an antigen-binding molecule or a constituent polypeptide thereof comprises an epitope tag, e.g. a His, (e.g. 6XHis), FLAG, c-Myc, StrepTag, haemagglutinin, E, calmodulin-binding protein (CBP), glutathione-s-transferase (GST), maltose-binding protein (MBP), thioredoxin, S-peptide, T7peptide, SH2 domain, avidin, streptavidin, and haptens (e.g. biotin, digoxigenin, dinitrophenol), optionally at the N- or C- terminus of the antigen-binding molecule / polypeptide.In some embodiments, an antigen-binding molecule or a constituent polypeptide thereof polypeptide comprises a moiety having a detectable activity, e.g. an enzymatic moiety. Enzymatic moieties include e.g. luciferases, glucose oxidases, galactosidases (e.g. beta-galactosidase), glucorinidases, phosphatases (e.g. alkaline phosphatase), peroxidases (e.g. horseradish peroxidase) and cholinesterases.Nucleic acids and vectorsThe present disclosure provides a nucleic acid, or a plurality of nucleic acids, encoding an antigen-binding molecule / antigen-binding polypeptide complex or a constituent polypeptide thereof according to the present disclosure. In some embodiments, the nucleic acid(s) comprise or consist of DNA and / or RNA.An antigen-binding molecule / antigen-binding polypeptide complex or a constituent polypeptide thereof according to the present disclosure may be produced within a cell by translation of RNA encoding the polypeptide(s). An antigen-binding molecule / antigen-binding polypeptide complex or a constituent polypeptide thereof may be produced within a cell by transcription from nucleic acid encoding the polypeptide(s), and subsequent translation of the transcribed RNA.In some embodiments, the nucleic acid(s) may be, or may be comprised / contained in, a vector, or a plurality of vectors. A ‘vector’ as used herein is a nucleic acid molecule used as a vehicle to transfer exogenous nucleic acid into a cell.Accordingly, the present disclosure also provides a vector, or plurality of vectors, comprising the nucleic acid or plurality of nucleic acids according to the present disclosure. The vector may facilitate delivery of the nucleic acid(s) encoding a polypeptide according to the present disclosure to a cell. The vector may be an expression vector comprising elements required for expressing a polypeptide according to the present disclosure. The vector may comprise elements facilitating integration of the nucleic acid(s) into the genomic DNA of cell into which the vector is introduced.Nucleic acids and vectors according to the present disclosure may be provided in purified or isolated form, i.e. from other nucleic acid, or naturally-occurring biological material.A vector may be a vector for expression of the nucleic acid in the cell (i.e. an expression vector). Such vectors may include a promoter sequence operably linked to a nucleotide sequence encoding an antigenbinding molecule or polypeptide according to the present disclosure. A vector may also include a termination codon (i.e. 3’ in the nucleotide sequence of the vector to the nucleotide sequence encoding the polypeptide(s)) and expression enhancers. Any suitable vectors, promoters, enhancers and termination codons known in the art may be used to express a peptide or polypeptide from a vector according to the present disclosure.The term ‘operably linked’ may include the situation where nucleic acid encoding a polypeptide according to the present disclosure and regulatory nucleic acid sequence(s) (e.g. a promoter and / or enhancers) are covalently linked in such a way as to place the expression of the nucleic acid encoding a polypeptide under the influence or control of the regulatory nucleic acid sequence(s) (thereby forming an expression cassette). Thus, a regulatory sequence is operably linked to the selected nucleic acid sequence if the regulatory sequence is capable of effecting transcription of the nucleic acid sequence. The resulting transcript(s) may then be translated into the desired polypeptide(s).Vectors contemplated in connection with the present disclosure include DNA vectors, RNA vectors, plasmids (e.g. conjugative plasmids (e.g. F plasmids), non-conjugative plasmids, R plasmids, col plasmids, episomes), viral vectors (e.g. retroviral vectors, e.g. gammaretroviral vectors (e.g. murine Leukemia virus (MLV)-derived vectors, e.g. SFG vector), lentiviral vectors, adenovirus vectors, adeno- associated virus vectors, vaccinia virus vectors and herpesvirus vectors), transposon-based vectors, and artificial chromosomes (e.g. yeast artificial chromosomes), e.g. as described in Maus et al., Annu Rev Immunol (2014) 32:189-225 and Morgan and Boyerinas, Biomedicines (2016) 4:9, which are both hereby incorporated by reference in their entirety. In some embodiments, a vector according to the present disclosure is a lentiviral vector.In some embodiments, the vector may be a eukaryotic vector, i.e. a vector comprising the elements necessary for expression of protein from the vector in a eukaryotic cell. In some embodiments, the vector may be a mammalian vector, e.g. comprising a cytomegalovirus (CMV) or SV40 promoter to drive protein expression.Constituent polypeptides of an antigen-binding molecule / antigen-binding polypeptide complex according to the present disclosure may be encoded by different nucleic acids of the plurality of nucleic acids, or by different vectors of the plurality of vectors.Producing the antigen-binding moleculesAntigen-binding molecules according to the present disclosure may be prepared according to methods for the production polypeptides known to the skilled person.Polypeptides may be prepared by chemical synthesis, e.g. liquid or solid phase synthesis. For example, peptides / polypeptides can by synthesized using the methods described in, for example, Chandrudu et al., Molecules (2013), 18: 4373-4388, which is hereby incorporated by reference in its entirety.Alternatively, antigen-binding molecules and polypeptides may be produced by recombinant expression. Molecular biology techniques suitable for recombinant production of polypeptides are well known in the art, such as those set out in Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th Edition), Cold Spring Harbor Press, 2012, and in Nat Methods. (2008); 5(2): 135-146 both of which are hereby incorporated by reference in their entirety. Methods for the recombinant production of antigen-binding molecules are also described in Frenzel et al., Front Immunol. (2013); 4: 217 and Kunert and Reinhart,Appl Microbiol Biotechnol. (2016) 100: 3451-3461 , both of which are hereby incorporated by reference in their entirety.In some cases the antigen-binding molecule of the present disclosure are comprised of more than one polypeptide chain. In such cases, production of the antigen-binding molecules may comprise transcription and translation of more than one polypeptide, and subsequent association of the polypeptide chains to form a polypeptide complex.The skilled person is able to design and prepare antigen-binding polypeptides / polypeptide complexes. Methods for producing antigen-binding polypeptides / polypeptide complexes include chemically crosslinking antigen-binding molecules or antibody fragments, e.g. with reducible disulphide or nonreducible thioether bonds, for example as described in Segal and Bast, 2001 . Production of Bispecific Antigen-binding molecules. Current Protocols in Immunology. 14:IV:2.13:2.13.1— 2.13.16, which is hereby incorporated by reference in its entirety. For example, A / -succinimidyl-3-(-2-pyridyldithio)-propionate (SPDP) can be used to chemically crosslink e.g. Fab fragments via hinge region SH- groups, to create disulfide-linked bispecific F(ab)2 heterodimers. Other methods for producing bispecific antigen-binding polypeptides / polypeptide complexes include fusing antibody-producing hybridomas e.g. with polyethylene glycol, to produce a quadroma cell capable of secreting bispecific antibody, for example as described in D. M. and Bast, B. J. 2001. Production of Bispecific Antigen-binding molecules. Current Protocols in Immunology. 14:IV:2.13:2.13.1-2.13.16.For recombinant production according to the present disclosure, any cell suitable for the expression of polypeptides may be used. The cell may be a prokaryote or eukaryote. In some embodiments, the cell is a prokaryotic cell, such as a cell of archaea or bacteria. In some embodiments, the bacteria may be Gram-negative bacteria such as bacteria of the family Enterobacteriaceae, for example Escherichia coli. In some embodiments, the cell is a eukaryotic cell such as a yeast cell, a plant cell, insect cell or a mammalian cell, e.g. a cell described hereinabove. In some cases, the cell is not a prokaryotic cell because some prokaryotic cells do not allow for the same folding or post-translational modifications as eukaryotic cells. In addition, very high expression levels are possible in eukaryotes and proteins can be easier to purify from eukaryotes using appropriate tags. Specific plasmids may also be utilised which enhance secretion of the protein into the media.In some embodiments polypeptides may be prepared by cell-free-protein synthesis (CFPS), e.g. according to a system described in Zemella et al. Chembiochem (2015) 16(17): 2420-2431 , which is hereby incorporated by reference in its entirety.Production of antigen-binding polypeptides / polypeptide complexes may involve culture or fermentation of a eukaryotic cell modified to express the polypeptide(s) of interest. The culture or fermentation may be performed in a bioreactor provided with an appropriate supply of nutrients, air / oxygen and / or growth factors. Secreted proteins can be collected by partitioning culture media / fermentation broth from the cells, extracting the protein content, and separating individual proteins to isolate secreted polypeptide(s). Culture, fermentation and separation techniques are well known to those of skill in the art, and aredescribed, for example, in Green and Sambrook, Molecular Cloning: A Laboratory Manual (4thEdition; incorporated by reference herein above). Bioreactors include one or more vessels in which cells may be cultured. Culture in the bioreactor may occur continuously, with a continuous flow of reactants into, and a continuous flow of cultured cells from, the reactor. Alternatively, the culture may occur in batches. The bioreactor monitors and controls environmental conditions such as pH, oxygen, flow rates into and out of, and agitation within the vessel such that optimum conditions are provided for the cells being cultured.Following culturing the cells that express the polypeptide(s), the polypeptide(s) of interest may be isolated. Any suitable method for separating proteins from cells known in the art may be used. In order to isolate the polypeptide, it may be necessary to separate the cells from nutrient medium. If the polypeptide(s) are secreted from the cells, the cells may be separated by centrifugation from the culture media that contains the secreted polypeptide(s) of interest. If the polypeptide(s) of interest collect within the cell, protein isolation may comprise centrifugation to separate cells from cell culture medium, treatment of the cell pellet with a lysis buffer, and cell disruption e.g. by sonification, rapid freeze-thaw or osmotic lysis.It may then be desirable to isolate the polypeptide(s) of interest from the supernatant or culture medium, which may contain other protein and non-protein components. A common approach to separating protein components from a supernatant or culture medium is by precipitation. Proteins of different solubilities are precipitated at different concentrations of precipitating agent such as ammonium sulfate. For example, at low concentrations of precipitating agent, water soluble proteins are extracted. Thus, by adding different increasing concentrations of precipitating agent, proteins of different solubilities may be distinguished. Dialysis may be subsequently used to remove ammonium sulfate from the separated proteins. Other methods for distinguishing different proteins are known in the art, for example ion exchange chromatography and size chromatography. These may be used as an alternative to precipitation or may be performed subsequently to precipitation.Once the polypeptide(s) of interest have been isolated from culture it may be desired or necessary to concentrate the polypeptide(s). A number of methods for concentrating proteins are known in the art, such as ultrafiltration or lyophilisation.Antigen-binding polypeptides / polypeptide complexes according to the present disclosure may be conjugated to linker-payload moieties according to the present disclosure by any suitable techniques, which are well known to the skilled person and routinely employed in the art.General methods for the conjugation of antigen-binding polypeptides / polypeptide complexes to linkerpayload moieties are described e.g. in Chudasama et al., Nature Chemistry, (2016), 8:114-119, Baah et al., Molecules. (2021) 26(10): 2943, and Walsh et a!., Chem. Soc. Rev. (2021) 50:1305-1353, all of which are hereby incorporated by reference in their entirety. Conjugation of antigen-binding moieties and linkerpayload moieties and purification of antigen-binding molecules produced by such conjugation is described e.g. in Beck et al., (2017) Nat Rev Drug Discov 16: 315-337; Peters and Brown Biosci Rep (2015) 35: art:e00225; McCombs and Owen, The AAPS Journal (2015) 17: 339-351 ; Jackson, Org Process Res Dev(2016) 20: 852-866; and Olivier and Hurvitz, Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcome to Target Cancer (2016) Wiley.The present disclosure also provides an antigen-binding molecule obtained or obtainable by the methods of the present disclosure.Cells comprising / expressing the antigen-binding polypeptides and their constituent polypeptidesThe present disclosure also provides a cell comprising or expressing an antigen-binding molecule / antigen-binding polypeptide complex or a constituent polypeptide thereof according to the present disclosure. Also provided is a cell comprising or expressing a nucleic acid, a plurality of nucleic acids, a vector or a plurality of vectors according to the present disclosure.It will be appreciated that where cells are referred to herein in the singular ( / .e. ‘a / the cell’), pluralities / populations of such cells are also contemplated.The cell may be a eukaryotic cell, e.g. a mammalian cell. The mammal may be a primate (rhesus, cynomolgus, non-human primate or human) or a non-human mammal (e.g. rabbit, guinea pig, rat, mouse or other rodent (including any animal in the order Rodentia), cat, dog, pig, sheep, goat, cattle (including cows, e.g. dairy cows, or any animal in the order Bos), horse (including any animal in the order Equidae), donkey, and non-human primate).In some embodiments, the cell is, or is derived from, a cell type commonly used for the expression of polypeptides for use in therapy in humans. Exemplary cells are described e.g. in Kunert and Reinhart, Appl Microbiol Biotechnol. (2016) 100:3451-3461 (hereby incorporated by reference in its entirety), and include e.g. CHO, HEK 293, PER.C6, NS0 and BHK cells. In preferred embodiments, the cell is, or is derived from, a CHO cell.The present disclosure also provides a method for producing a cell comprising a nucleic acid(s) or vector(s) according to the present disclosure, comprising introducing a nucleic acid, a plurality of nucleic acids, a vector or a plurality of vectors according to the present disclosure into a cell. In some embodiments, introducing an isolated nucleic acid(s) or vector(s) according to the present disclosure into a cell comprises transformation, transfection, electroporation or transduction (e.g. retroviral transduction).The present disclosure also provides a method for producing a cell expressing / comprising an antigenbinding polypeptide complex or a constituent polypeptide thereof according to the present disclosure, comprising introducing a nucleic acid, a plurality of nucleic acids, a vector or a plurality of vectors according to the present disclosure in a cell. In some embodiments, the methods additionally comprise culturing the cell under conditions suitable for expression of the nucleic acid(s) or vector(s) by the cell. In some embodiments, the methods are performed in vitro.The present disclosure also provides cells obtained or obtainable by the methods according to the present disclosure.Also provided is a cell comprising a CAR according to the present disclosure. The CAR according to the present disclosure may be used to generate CAR-expressing immune cells, e.g. CAR-T or CAR-NK cells. Engineering of CARs into immune cells may be performed during culture, in vitro.CompositionsThe present disclosure provides a composition comprising an antigen-binding molecule / polypeptide / polypeptide complex according to the present disclosure.The antigen-binding molecules described herein may be formulated as pharmaceutical compositions or medicaments for clinical use and may comprise a pharmaceutically-acceptable carrier, diluent, excipient or adjuvant. Thus, the present disclosure provides a pharmaceutical composition / medicament comprising an antigen-binding molecule described herein.The pharmaceutical compositions / medicaments of the present disclosure may comprise one or more pharmaceutically-acceptable carriers (e.g. liposomes, micelles, microspheres, nanoparticles), diluents / excipients (e.g. starch, cellulose, a cellulose derivative, a polyol, dextrose, maltodextrin, magnesium stearate), adjuvants, fillers, buffers, preservatives (e.g. vitamin A, vitamin E, vitamin C, retinyl palmitate, selenium, cysteine, methionine, citric acid, sodium citrate, methyl paraben, propyl paraben), anti-oxidants (e.g. vitamin A, vitamin E, vitamin C, retinyl palmitate, selenium), lubricants (e.g. magnesium stearate, talc, silica, stearic acid, vegetable stearin), binders (e.g. sucrose, lactose, starch, cellulose, gelatin, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), xylitol, sorbitol, mannitol), stabilisers, solubilisers, surfactants (e.g., wetting agents), masking agents or colouring agents (e.g. titanium oxide).The term ‘pharmaceutically-acceptable’ as used herein pertains to compounds, ingredients, materials, compositions, dosage forms, etc., which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of the subject in question (e.g. a human subject) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each carrier, diluent, excipient, adjuvant, filler, buffer, preservative, anti-oxidant, lubricant, binder, stabiliser, solubiliser, surfactant, masking agent, colouring agent, flavouring agent or sweetening agent of a composition according to the present disclosure must also be ‘acceptable’ in the sense of being compatible with the other ingredients of the formulation. Suitable carriers, diluents, excipients, adjuvants, fillers, buffers, preservatives, anti-oxidants, lubricants, binders, stabilisers, solubilisers, surfactants, masking agents, colouring agents, flavouring agents or sweetening agents can be found in standard pharmaceutical texts, for example, Remington’s ‘The Science and Practice of Pharmacy’ (Ed. A. Adejare), 23rdEdition (2020), Academic Press.Pharmaceutical compositions and medicaments of the present disclosure may be formulated for topical, parenteral, systemic, intracavitary, intravenous, intra-arterial, intramuscular, intrathecal, intraocular, intraconjunctival, intratumoral, subcutaneous, intradermal, intrathecal, oral or transdermal routes of administration. In some embodiments, a pharmaceutical composition / medicament may be formulated for administration by injection or infusion, or administration by ingestion.Suitable formulations may comprise the antigen-binding molecule provided in a sterile or isotonic medium. Medicaments and pharmaceutical compositions may be formulated in fluid, including gel, form. Fluid formulations may be formulated for administration by injection or infusion (e.g. via catheter) to a selected region of the human or animal body.In some embodiments, the pharmaceutical compositions / medicament is formulated for injection or infusion, e.g. into a blood vessel, tissue / organ of interest, or a tumor.The present disclosure also provides methods for the production of pharmaceutically useful compositions, such methods of production may comprise one or more steps selected from: producing an antigen-binding molecule described herein; isolating / purifying an antigen-binding molecule described herein; and / or mixing an antigen-binding molecule described herein with a pharmaceutically-acceptable carrier, adjuvant, excipient or diluent.For example, a further aspect of the present disclosure relates to a method of formulating or producing a medicament or pharmaceutical composition for use in the treatment of a disease / condition (e.g. a disease / condition described herein), the method comprising formulating a pharmaceutical composition or medicament by mixing an antigen-binding molecule described herein with a pharmaceutically-acceptable carrier, adjuvant, excipient or diluent.Therapeutic and prophylactic applicationsThe antigen-binding molecules / polypeptides and compositions described herein find use in therapeutic and prophylactic intervention for disease, e.g. cancers.The present disclosure provides an antigen-binding molecule or composition described herein for use in a method of medical treatment or prophylaxis. Also provided is an antigen-binding molecule or composition described herein for use in a method of treating or preventing a cancer (e.g. a cancer described herein). Also provided is the use of an antigen-binding molecule or composition described herein in the manufacture of a medicament for treating or preventing a cancer (e.g. a cancer described herein). Also provided is a method of treating or preventing a cancer (e.g. a cancer described herein) in a subject, comprising administering to a subject a therapeutically or prophylactically effective amount of an antigenbinding molecule or composition described herein.It will be appreciated that the antigen-binding molecules and compositions of the present disclosure may be used for the treatment / prevention of any disease / condition that would derive therapeutic or prophylactic benefit from a reduction in the level of expression or activity of VISTA, or a reduction in the number or activity of cells comprising / expressing VISTA.It will be appreciated that the antigen-binding molecules and compositions of the present disclosure may be used for the treatment / prevention of any disease / condition that would derive therapeutic orprophylactic benefit from a reduction in the number and / or activity of cells expressing VISTA (e.g. MDSCs). It will also be clear that the therapeutic and prophylactic utility of the present disclosure extends to essentially any disease / condition which would benefit from a reduction in the number or activity of MDSCs and / or other cells expressing VISTA, e.g. tumor-associated macrophages (TAMs) and neutrophils. Antagonism of VISTA effectively releases effector immune cells from suppression by MDSCs and / or other cells expressing VISTA.For example, the disease / condition may be a disease / condition in which VISTA, or cells expressing / overexpressing VISTA (e.g. MDSCs) are pathologically-implicated, e.g. a disease / condition in which an increased level / activity of VISTA, or an increase in the number / proportion of cells comprising / expressing VISTA (e.g. MDSCs) is positively associated with the onset, development or progression of the disease / condition, and / or severity of one or more symptoms of the disease / condition. In some embodiments, an increased level / activity of VISTA, or an increase in the number / proportion of cells comprising / expressing VISTA (e.g. MDSCs) may be a risk factor for the onset, development or progression of the disease / condition.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a disease / condition characterized by an increase in the number / proportion / activity of cells expressing VISTA (e.g. MDSCs), e.g. as compared to the number / proportion / activity of cells expressing VISTA (e.g. MDSCs) in the absence of the disease / condition.Expression may be determined by any suitable means. Expression may be gene expression or protein expression. Gene expression can be determined e.g. by detection of mRNA encoding VISTA, for example by quantitative real-time PCR (qRT-PCR). Protein expression can be determined e.g. by antibody-based methods, for example by western blot, immunohistochemistry, immunocytochemistry, flow cytometry, or ELISA.In some embodiments the disease / condition to be treated / prevented is a cancer. The methods may be effective to reduce the development or progression of a cancer, alleviation of the symptoms of a cancer or reduction in the pathology of a cancer. The methods may be effective to prevent progression of the cancer, e.g. to prevent worsening of, or to slow the rate of development of, the cancer. In some embodiments, the methods may lead to an improvement in the cancer, e.g. a reduction in the symptoms of the cancer or reduction in some other correlate of the severity / activity of the cancer. In some embodiments, the methods may prevent development of the cancer to a later stage (e.g. a chronic stage or metastasis).It will be appreciated that the antigen-binding molecules are useful for the treatment of cancers in general, because antigen-binding molecules of the present invention are useful to release effector immune cells from MDSC-mediated suppression or suppression by cells expressing VISTA, and thereby enhance the anticancer immune response.As used herein, a ‘cancer’ may be or comprise any unwanted cell proliferation (or any disease manifesting itself by unwanted cell proliferation), neoplasm or tumor. The cancer may be benign or malignant. The cancer may be primary or secondary (metastatic). A neoplasm or tumor may be any abnormal growth or proliferation of cells and may be located in any tissue. The cancer may be of tissues / cells derived from e.g. the adrenal gland, adrenal medulla, anus, appendix, bladder, blood, bone, bone marrow, brain, breast, cecum, central nervous system (including or excluding the brain) cerebellum, cervix, colon, duodenum, endometrium, epithelial cells (e.g. renal epithelia), gallbladder, biliary tract, oesophagus, glial cells, heart, ileum, jejunum, kidney, lacrimal glad, larynx, liver, lung, lymph, lymph node, lymphoblast, maxilla, mediastinum, mesentery, myometrium, nasopharynx, omentum, oral cavity, ovary, pancreas, parotid gland, peripheral nervous system, peritoneum, pleura, prostate, salivary gland, sigmoid colon, skin, small intestine, soft tissues, spleen, stomach, testis, thymus, thyroid gland, tongue, tonsil, trachea, uterus, vulva, white blood cells.Tumors to be treated may be nervous or non-nervous system tumors. Nervous system tumors may originate either in the central or peripheral nervous system, e.g. glioma, medulloblastoma, meningioma, neurofibroma, ependymoma, Schwannoma, neurofibrosarcoma, astrocytoma and oligodendroglioma. Non-nervous system cancers / tumors may originate in any other non-nervous tissue; examples include melanoma, mesothelioma, lymphoma, myeloma, leukemia, Non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma, chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), cutaneous T-cell lymphoma (CTCL), chronic lymphocytic leukemia (CLL), hepatoma, epidermoid carcinoma, prostate carcinoma, breast cancer, lung cancer, colon cancer, ovarian cancer, pancreatic cancer, thymic carcinoma, NSCLC, hematologic cancer and sarcoma.In some embodiments, the cancer to be treated / prevented comprises cells expressing VISTA. In some embodiments, the cancer to be treated / prevented is a cancer which is positive for VISTA. In some embodiments, the cancer comprises cells that overexpress VISTA. Overexpression can be determined by detection of a level of expression which is greater than the level of expression by equivalent non- cancerous cells / non-tumor tissue.In some embodiments, a subject may be selected for treatment described herein based on the detection of an increase in the number / proportion / activity of cells expressing VISTA (e.g. MDSCs), e.g. in the periphery, or in an organ / tissue which is affected by the disease / condition (e.g. an organ / tissue in which the symptoms of the disease / condition manifest), or by the presence of cells expressing VISTA (e.g. MDSCs or tumor-associated macrophages) in a tumor. The disease / condition may affect any tissue or organ or organ system. In some embodiments, the disease / condition may affect several tissues / organs / organ systems.In some embodiments a subject may be selected for therapy / prophylaxis in accordance with the present invention based on determination that the subject has an increase in the number / proportion / activity of cells expressing VISTA (e.g. MDSCs) in the periphery or in an organ / tissue relative to the number / proportion / activity of such cells in a healthy subject, or based on determination that the subject has a tumor comprising cells expressing VISTA (e.g. MDSCs).Myeloid Derived Suppressor Cell (MDSC)-mediated suppression of immune response has been identified in multiple solid tumors and lymphomas. MDSCs are elevated in advanced colorectal cancer (Toor et al., Front Immunol. 2016; 7:560). MDSCs are also observed in breast cancer, and the percentage of MDSCs in the peripheral blood is increased in patients with later stage breast cancer (Markowitz et al, Breast Cancer Res Treat. 2013 Jul; 140(1 ):13-21). MDSC abundance is also correlated with poor prognosis in solid tumors (Charoentong et al., Cell Rep. 2017 Jan 3; 18(1):248-262).MDSCs exert suppression over T cells through multiple mechanisms, including the production of reactive oxygen species, nitric oxide, and arginase. These ultimately lead to suppression of DC, NK and T cell activity and increased tumor burden (Umansky et al., Vaccines (Basel) (2016) 4(4):36). MDSCs also contribute to the tumor development and metastasis through the production of soluble factors such as matrix metalloproteinases, VEGF, bFGF, TGF-0 and S100A8 / A9 which promote neovascularisation, invasion, proliferation and metastasis.VISTA is expressed primarily on MDSCs, and is therefore an attractive target for intervention to inhibit MDSC-mediated suppression of effector immune cell function.As noted hereinabove, the articles of the present disclosure may be used for the treatment / prevention of any disease / condition that would derive therapeutic or prophylactic benefit from a reduction in the number and / or activity of VISTA-expressing cells, such as MDSCs, tumor-associated macrophages (TAMs) and neutrophils. It will be appreciated that the antigen-binding molecules are useful for the treatment of cancers in general, because antigen-binding molecules of the present disclosure are useful to release effector immune cells from suppression by cells expressing VISTA (e.g. MDSCs, TAMs, neutrophils), and thereby enhance the anticancer immune response.MDSCs are elevated in advanced colorectal cancer (Toor et al., Front Immunol. 2016; 7:560). MDSCs are also observed in breast cancer, and the percentage of MDSCs in the peripheral blood is increased in patients with later stage breast cancer (Markowitz et al., Breast Cancer Res Treat. 2013 Jul; 140(1 ):13- 21). MDSC abundance is also correlated with poor prognosis in solid tumors (Charoentong et al., Cell Rep. 2017 Jan 3; 18(1):248-262), and MDSCs are enriched in liver cancer models (Connolly et al., J Leukoc Biol. (2010) 87(4):713-25). Prostate and breast carcinomas, melanomas, colorectal cancer and Lewis lung carcinoma have been reported to produce chemokines which attract MDSCs and contribute to immune suppression (Umansky et al., Vaccines (Basel) (2016) 4(4):36)), and MDSCs in pancreatic cancer patients have been positively correlated with tumor burden (Xu et al., Hepatobiliary Pancreat Dis Int. (2016) 15(1 ):99-105). VISTA has also been reported to be a target for the treatment of ovarian cancer (see e.g. US 9,631 ,018 B2) and lymphoma (see e.g. WO 2017 / 023749 A1 ). Blando et al. Proc Natl Acad Sci U S A. (2019) 116(5):1692-1697 recently reported significant infiltration of VISTA-expressing myeloid cells in pancreatic cancer, and expansion of VISTA-expressing myeloid cells has been observed following treatment with CTLA4 antagonist in prostate cancer, and both pre- and post- treatment with PD-L1 antagonist in melanoma.Alternatively, or additionally, a cancer characterized by ‘the presence of’ cells expressing VISTA may be characterized by the presence of cells expressing VISTA in the vicinity of ( / .e. proximal to) cells of the cancer. The cancer may comprise infiltration of cells expressing VISTA. The cancer may comprise a tumor displaying infiltration of cells expressing VISTA. In connection with such embodiments, the cells expressing VISTA are not necessarily cells of the cancer, and may e.g. be non-cancerous cells. In some embodiments, the cells are immune cells. The immune cells expressing VISTA may be or comprise cells of hematopoietic origin, e.g. neutrophils, eosinophils, basophils, dendritic cells, lymphocytes, or monocytes. In some embodiments, the immune cells expressing VISTA may be or comprise lymphocytes, e.g. a T cells, B cells, NK cells, NKT cells, innate lymphoid cells (ILCs), or precursors thereof. In some embodiments, the immune cells expressing VISTA are effector immune cells (e.g. CD8+ T cells, CD8+ cytotoxic T lymphocytes (CD8+ CTLs), CD4+ T cells, CD4+ T helper cells, NK cells, IFNy-producing cells, memory T cells, central memory T cells, antigen-experienced T cells and / or CD45RO+ T cells). In some embodiments, the immune cells expressing VISTA are antigen-presenting cells (APCs), macrophages, dendritic cells, T cells (e.g. CD8+ T cells) and / or MDSCs. In embodiments wherein the cancer comprises infiltration of immune cells expressing VISTA, or wherein the cancer comprises a tumor displaying infiltration of such immune cells, the immune cells may be referred to as tumor-infiltrating immune cells.For example, a cancer characterized by the presence of cells expressing VISTA may comprise a tumor comprising cells (e.g. non-cancerous cells, e.g. tumor-infiltrating immune cells) expressing VISTA.It will be appreciated that cells that are said to be ‘in the vicinity of or ‘proximal to’ cells of a cancer are provided in close physical proximity to cells of a cancer, e.g. in vivo in a subject having such a cancer. In some embodiments, cells which are in the vicinity of / proximal to cells of a cancer are comprised in the same organ / tissue as cells of the cancer. In some embodiments, cells which are in the vicinity of / proximal to cells of a cancer are comprised in a tumor of the cancer. In some embodiments, cells which are in the vicinity of / proximal to cells of a cancer are in contact with cells of the cancer.In some embodiments, the cancer to be treated / prevented comprises cells expressing VISTA. In some embodiments, the cancer to be treated / prevented comprises cancerous cells expressing VISTA. In some embodiments, the cells expressing VISTA are MDSCs (e.g. g-MDSCs and / or m-MDSCs). In some embodiments, the cancer comprises a tumor comprising cells expressing VISTA (e.g. MDSCs). In some embodiments, the cancer to be treated / prevented comprises a tumor comprising MDSCs. In some embodiments, the cancer to be treated / prevented comprises infiltration of cells expressing VISTA (e.g. MDSCs). In some embodiments, the cancer to be treated / prevented comprises a tumor displaying infiltration of cells expressing VISTA (e.g. MDSCs).In some embodiments, a cancer to be treated / prevented in accordance with the present disclosure is a cancer described in WO 2023 / 046979 A1 , which is hereby incorporated by reference in its entirety.In some embodiments, a cancer is selected from: a cancer comprising cells expressing / overexpressing VISTA, a cancer comprising infiltration of cells expressing VISTA (e.g. a cancer characterised by the presence of cells expressing VISTA in the vicinity of (i.e. proximal to) cells of the cancer; e.g. a cancercomprising a tumor displaying infiltration of cells expressing VISTA (e.g. VISTA-expressing MDSCs)), a hematological cancer, leukemia, acute myeloid leukemia, lymphoma, B cell lymphoma, T cell lymphoma, multiple myeloma, mesothelioma, a solid tumor, lung cancer, non-small cell lung cancer, gastric cancer, gastric carcinoma, colorectal cancer, colorectal carcinoma, colorectal adenocarcinoma, uterine cancer, uterine corpus endometrial carcinoma, breast cancer, triple negative breast cancer, triple negative breast invasive carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, thyroid cancer, thymoma, skin cancer, melanoma, cutaneous melanoma, kidney cancer, renal cell carcinoma, renal papillary cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck (SCCHN), ovarian cancer, ovarian carcinoma, ovarian serous cystadenocarcinoma, prostate cancer and / or prostate adenocarcinoma. In some embodiments, the cancer is selected from: a solid tumor, colorectal cancer (e.g. colon carcinoma, colon adenocarcinoma), pancreatic cancer, breast cancer (e.g. triple-negative breast cancer), liver cancer, prostate cancer, ovarian cancer, head and neck cancer, leukemia (e.g. T cell leukemia), lymphoma, melanoma, thymoma or lung cancer (e.g. non-small cell lung cancer). In some embodiments, the cancer is mesothelioma (e.g. epithelioid mesothelioma).In some embodiments, the cancer may be a relapsed cancer. As used herein, a ‘relapsed’ cancer refers to a cancer which responded to a treatment (e.g. a first line therapy for the cancer), but which has subsequently re-emerged / progressed, e.g. after a period of remission. For example, a relapsed cancer may be a cancer whose growth / progression was inhibited by a treatment (e.g. a first line therapy for the cancer), and which has subsequently grown / progressed. A cancer that is relapsed with respect to given treatment may be described as having acquired resistance to such treatment.In some embodiments, the cancer may be a refractory cancer. As used herein, a ‘refractory’ cancer refers to a cancer which has not responded to a treatment (e.g. a first line therapy for the cancer). For example, a refractory cancer may be a cancer whose growth / progression was not inhibited by a treatment (e.g. a first line therapy for the cancer). In some embodiments a refractory cancer may be a cancer for which a subject receiving treatment for the cancer did not display a partial or complete response to the treatment. A cancer that is refractory with respect to given treatment may be described as having intrinsic resistance to such treatment. Herein, where a cancer is described as being relapsed / refractory / resistant, etc. with respect to a given intervention, it may be simply described as being ‘relapsed / refractory / resistant to’ the relevant intervention.Treatment of a cancer in accordance with the methods of the present disclosure achieves one or more of the following treatment effects: reduces the number of cancer cells in the subject, reduces the size of a cancerous tumor / lesion in the subject, inhibits (e.g. prevents or slows) growth of cancer cells in the subject, inhibits (e.g. prevents or slows) growth of a cancerous tumor / lesion in the subject, inhibits (e.g. prevents or slows) the development / progression of a cancer (e.g. to a later stage, or metastasis), reduces the severity of symptoms of a cancer in the subject, increases survival of the subject (e.g. progression free survival or overall survival), reduces a correlate of the number or activity of cancer cells in the subject, and / or reduces cancer burden in the subject.Subjects may be evaluated in accordance with the Revised Criteria for Response Assessment: The Lugano Classification (described e.g. in Cheson et al., J Clin Oncol (2014) 32: 3059-3068, incorporated by reference hereinabove) in order to determine their response to treatment. In some embodiments, treatment of a subject in accordance with the methods of the present disclosure achieves one of the following: complete response, partial response, or stable disease.Prevention may refer to prevention of development of a cancer, and / or prevention of worsening of a cancer, e.g. prevention of progression of a cancer, e.g. to a later stage (e.g. metastasis).In some embodiments, administration of an antigen-binding molecule / composition according to the present disclosure may be associated with one or more of: inhibition of the development / progression of the cancer, a delay to / prevention of onset of the cancer, a reduction in / delay to / prevention of tumor growth, a reduction in / delay to / prevention of tissue invasion, a reduction in / delay to / prevention of metastasis, a reduction in the severity of one or more symptoms of the cancer, a reduction in the number of cancer cells, a reduction in the cancer burden, a reduction in tumor size / volume, and / or an increase in survival of subjects having the cancer (e.g. progression free survival or overall survival).In accordance with various aspects of the present disclosure, a method of treating and / or preventing a cancer according to the present disclosure may comprise inhibiting the growth of a tumor, reducing the size / volume of a tumor and / or increasing the survival of a subject having the cancer.In accordance with various aspects of the present disclosure, methods are provided which are for, or which comprise (e.g. in the context of treatment / prevention of a cancer, e.g. a cancer described herein), one or more of the following: binding to cells expressing VISTA; inhibiting the proliferation of VISTA-expressing cells; killing cells expressing VISTA; inhibiting tumor growth and / or reducing tumor size / volume, e.g. of a VISTA-expressing cancer; and / or increasing the survival of subjects having a cancer, e.g. a VISTA-expressing cancer.Also provided are antigen-binding molecules and compositions according to the present disclosure for use in such methods, and the use of antigen-binding molecules and compositions according to the present disclosure in manufacture of compositions (e.g. medicaments) for use in such methods. It will be appreciated that the methods typically comprise administering an antigen-binding molecule according to the present disclosure to a subject.Similarly, one or more of the following may be observed in a subject following therapeutic or prophylactic intervention in accordance with the present disclosure (e.g. compared to the level / number / proportion etc. prior to intervention): inhibition of proliferation of VISTA-expressing cells; killing of cells expressing VISTA;inhibition of tumor growth and / or reduction of tumor size / volume, e.g. of a VISTA-expressing cancer; and / or increased survival of a subject having a cancer, e.g. a VISTA-expressing cancer.In some embodiments, therapeutic / prophylactic intervention in accordance with the present disclosure may be described as being ‘associated with’ one or more of the effects described in the preceding paragraph. The skilled person is readily able to evaluate such properties using techniques that are routinely practiced in the art.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low number and / or proportion of antigen-specific CD8+ T cells.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low level of CD8+ T cell activity.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high level of T cell exhaustion.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high number and / or proportion of MHCH-negative tumor-associated macrophages (TAMs).In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low number and / or proportion of M1-type macrophages.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low level of M1-type macrophage activity.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low number and / or proportion of effector memory T cells, e.g. in the peripheral blood.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high number and / or proportion of effector memory T cells, e.g. in the peripheral blood.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by a reduced or low number and / or proportion of effector memory CD4+ T cells, e.g. in the peripheral blood.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high number and / or proportion of effector memory CD4+ T cells, e.g. in the peripheral blood.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high number and / or proportion of non-classical monocytes, e.g. in the peripheral blood.In some embodiments, the disease / condition to be treated / prevented in accordance with the present disclosure is a cancer characterized by an increased or high number and / or proportion of conventional type 2 dendritic cells, e.g. in the peripheral blood.In some embodiments (e.g. embodiments wherein the antigen-binding molecule lacks an Fc region, or embodiments wherein the antigen-binding molecule comprises an Fc region which is not able to induce an Fc-mediated antibody effector function), the treatment does not induce / increase killing of VISTA- expressing cells. In some embodiments, the treatment does not reduce the number / proportion of VISTA- expressing cells.In some embodiments, the treatment (i) inhibits VISTA-mediated signalling, and (ii) does not induce / increase killing of VISTA-expressing cells. In some embodiments, the treatment (i) inhibits VISTA- mediated signalling, and (ii) does not reduce the number / proportion of VISTA-expressing cells.In some embodiments, the disease / condition in which the VISTA-expressing cells are pathologically implicated is an infectious disease, e.g. bacterial, viral, fungal, or parasitic infection. In some embodiments it may be particularly desirable to treat chronic / persistent infections, e.g. where such infections are associated with T cell dysfunction or T cell exhaustion. It is well established that T cell exhaustion is a state of T cell dysfunction that arises during many chronic infections (including viral, bacterial and parasitic), as well as in cancer (Wherry Nature Immunology Vol.12, No.6, p492-499, June 2011).Examples of bacterial infections that may be treated include infection by Bacillus spp., Bordetella pertussis, Clostridium spp., Corynebacterium spp., Vibrio chloerae, Staphylococcus spp., Streptococcus spp. Escherichia, Klebsiella, Proteus, Yersinia, Erwina, Salmonella, Listeria sp, Helicobacter pylori, mycobacteria (e.g. Mycobacterium tuberculosis) and Pseudomonas aeruginosa. For example, the bacterial infection may be sepsis or tuberculosis. Examples of viral infections that may be treated include infection by influenza virus, measles virus, hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), lymphocytic choriomeningitis virus (LCMV), Herpes simplex virus and human papilloma virus (HPV). Examples of fungal infections that may be treated include infection by Alternaria sp, Aspergillus sp, Candida sp and Histoplasma sp. The fungal infection may be fungal sepsis or histoplasmosis. Examples of parasitic infections that may be treated include infection by Plasmodium species (e.g. Plasmodium falciparum, Plasmodium yoeli, Plasmodium ovale, Plasmodium vivax, orPlasmodium chabaudi chabaudi). The parasitic infection may be a disease such as malaria, leishmaniasis and toxoplasmosis.Administration of the antigen-binding molecules and compositions of the present disclosure is preferably in a ‘therapeutically-effective’ or ‘prophylactically-effective’ amount, this being sufficient to show therapeutic or prophylactic benefit to the subject. The actual amount administered, and rate and timecourse of administration, will depend on the nature and severity of the disease / condition and the particular article administered. Prescription of treatment, e.g. decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors, and typically takes account of the disease / disorder to be treated, the condition of the individual subject, the site of delivery, the method of administration and other factors known to practitioners. Examples of the techniques and protocols mentioned above can be found in Remington’s ‘The Science and Practice of Pharmacy’ (Ed. A. Adejare), 23rdEdition (2020), Academic Press.Administration of the antigen-binding molecules and compositions of the present disclosure may be e.g. parenteral, systemic, topical, intracavitary, intravascular, intravenous, intra-arterial, intramuscular, intrathecal, intraocular, intraconjunctival, intratumoral, subcutaneous, intradermal, oral or transdermal. Administration may be by injection, infusion or ingestion.In some aspects and embodiments, articles of the present disclosure may be administered to a tissue / organ of interest (e.g. a tissue / organ affected by the disease / condition, e.g. a tissue / organ in which symptoms of the disease / condition manifest). In some aspects and embodiments, articles of the present disclosure may be administered to the blood (i.e. intravenous / intra-arterial administration) by injection or infusion (e.g. via cannula), or may be administered subcutaneously or orally. In some aspects and embodiments, articles of the present disclosure may be administered to a tumor.In some embodiments, therapeutic or prophylactic intervention according to the present disclosure may further comprise administering another agent for the treatment / prevention of the relevant disease / condition. Administration of antigen-binding molecules and compositions described herein may be alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated. Simultaneous administration refers to administration with another therapeutic agent together, for example as a pharmaceutical composition containing both agents (combined preparation), or immediately after each other (e.g. within 1 , 4, 6, 8 or 12 hours) and optionally via the same route of administration (e.g. to the same tissue, artery, vein or other blood vessel). Sequential administration refers to administration of one agent followed after a given time interval by separate administration of another agent. It is not required that the two agents are administered by the same route, although this is the case in some embodiments. The time interval may be any time interval.Said agent / treatment may be selected from chemotherapy, immunotherapy, radiotherapy, surgery, vaccination and / or hormone therapy. In some embodiments, the additional treatment comprises leukapheresis. In some embodiments, the additional treatment comprises a stem cell transplant.In some embodiments, the antigen-binding molecule is administered in combination with an agent capable of inhibiting signalling mediated by an immune checkpoint molecule other than VISTA. In some embodiments, the immune checkpoint molecule is e.g. PD-1 , CTLA-4, LAG-3, TIM-3, TIGIT or BTLA. In some embodiments, the antigen-binding molecule is administered in combination with an agent capable of promoting signalling mediated by a costimulatory receptor. In some embodiments, the costimulatory receptor is e.g. CD28, CD80, CD40L, CD86, 0X40, 4-1 BB, CD27 or IGOS.Accordingly, the present disclosure provides compositions comprising an article according to the present disclosure (e.g. an antigen-binding molecule according to the present disclosure) and an agent capable of inhibiting signalling mediated by an immune checkpoint molecule other than VISTA. Also provided are compositions comprising the articles of the present disclosure and an agent capable of promoting signalling mediated by a costimulatory receptor. Also provided is the use of such compositions in methods of medical treatment and prophylaxis of diseases / conditions described herein.Also provided are methods for treating / preventing diseases / conditions described herein comprising administering an article according to the present disclosure (e.g. an antigen-binding molecule according to the present disclosure) and an agent capable of inhibiting signalling mediated by an immune checkpoint molecule other than VISTA. Also provided are methods for treating / preventing diseases / conditions described herein comprising administering an article according to the present disclosure (e.g. an antigen-binding molecule according to the present disclosure) and an agent capable of promoting signalling mediated by a costimulatory receptor.Agents capable of inhibiting signalling mediated by immune checkpoint molecules are known in the art, and include e.g. antibodies capable of binding to immune checkpoint molecules or their ligands, and inhibiting signalling mediated by the immune checkpoint molecule. Other agents capable of inhibiting signalling mediated by an immune checkpoint molecule include agents capable of reducing gene / protein expression of the immune checkpoint molecule or a ligand for the immune checkpoint molecule (e.g. through inhibiting transcription of the gene(s) encoding the immune checkpoint molecule / ligand, inhibiting post-transcriptional processing of RNA encoding the immune checkpoint molecule / ligand, reducing stability of RNA encoding the immune checkpoint molecule / ligand, promoting degradation of RNA encoding the immune checkpoint molecule / ligand, inhibiting post-translational processing of the immune checkpoint molecule / ligand, reducing stability the immune checkpoint molecule / ligand, or promoting degradation of the immune checkpoint molecule / ligand), and small molecule inhibitors.Agents capable of promoting signalling mediated by costimulatory receptors are known in the art, and include e.g. agonist antibodies capable of binding to costimulatory receptors and triggering or increasing signalling mediated by the costimulatory receptor. Other agents capable of promoting signalling mediated by costimulatory receptors include agents capable of increasing gene / protein expression of the costimulatory receptor or a ligand for the costimulatory receptor (e.g. through promoting transcription of the gene(s) encoding the costimulatory receptor / ligand, promoting post-transcriptional processing of RNA encoding the costimulatory receptor / ligand, increasing stability of RNA encoding the costimulatory receptor / ligand, inhibiting degradation of RNA encoding the costimulatory receptor / ligand, promoting post-translational processing of the costimulatory receptor / ligand, increasing stability the costimulatory receptor / ligand, or inhibiting degradation of the costimulatory receptor / ligand), and small molecule agonists.In particular embodiments the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by PD-1 . The agent capable of inhibiting signalling mediated by PD-1 may be a PD-1- or PD-L1 -targeted agent. The agent capable of inhibiting signalling mediated by PD-1 may e.g. be an antibody capable of binding to PD-1 or PD-L1 and inhibiting PD-1 -mediated signalling. In some embodiments, the agent is an antagonist anti-PD-1 antibody. In some embodiments, the agent is an antagonist anti-PD-L1 antibody.In some embodiments, the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by CTLA-4. The agent capable of inhibiting signalling mediated by CTLA-4 may be a CTLA-4-targeted agent, or an agent targeted against a ligand for CTLA-4 such as CD80 or CD86. In some embodiments, the agent capable of inhibiting signalling mediated by CTLA-4 may e.g. be an antibody capable of binding to CTLA-4, CD80 or CD86 and inhibiting CTLA-4-mediated signalling.In some embodiments, the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by LAG-3. The agent capable of inhibiting signalling mediated by LAG-3 may be a LAG-3-targeted agent, or an agent targeted against a ligand for LAG-3 such as MHC class II. In some embodiments, the agent capable of inhibiting signalling mediated by LAG-3 may e.g. be an antibody capable of binding to LAG-3 or MHC class II and inhibiting LAG-3-mediated signalling.In some embodiments, the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by TIM-3. The agent capable of inhibiting signalling mediated by TIM-3 may be a TIM-3-targeted agent, or an agent targeted against a ligand for TIM-3 such as Galectin 9. In some embodiments, the agent capable of inhibiting signalling mediated by TIM-3 may e.g. be an antibody capable of binding to TIM-3 or Galectin 9 and inhibiting TIM- 3-mediated signalling.In some embodiments, the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by TIGIT. The agent capable of inhibiting signalling mediated by TIGIT may be a TIGIT-targeted agent, or an agent targeted against a ligand for TIGIT such as CD113, CD112 or CD155. In some embodiments, the agent capable of inhibiting signalling mediated by TIGIT may e.g. be an antibody capable of binding to TIGIT, CD113, CD112 or CD155 and inhibiting TIGIT-mediated signalling.In some embodiments, the antigen-binding molecule of the present disclosure is administered in combination with an agent capable of inhibiting signalling mediated by BTLA. The agent capable of inhibiting signalling mediated by BTLA may be a BTLA-targeted agent, or an agent targeted against aligand for BTLA such as HVEM. In some embodiments, the agent capable of inhibiting signalling mediated by BTLA may e.g. be an antibody capable of binding to BTLA or HVEM and inhibiting BTLA - mediated signalling.In some embodiments methods employing a combination of an antigen-binding molecule of the present disclosure and an agent capable of inhibiting signalling mediated by an immune checkpoint molecule (e.g. PD-1 and / or PD-L1) provide an improved treatment effect as compared to the effect observed when either agent is used as a monotherapy. In some embodiments, the combination of an antigen-binding molecule of the present disclosure and an agent capable of inhibiting signalling mediated by an immune checkpoint molecule (e.g. PD-1 and / or PD-L1) provide a synergistic (i.e. super-additive) treatment effect.In some embodiments, treatment with a combination comprising (i) an antigen-binding molecule of the present disclosure and (ii) an agent capable of inhibiting signalling mediated by an immune checkpoint molecule (e.g. PD-1 and / or PD-L1) may be associated with one or more of:• an improved treatment effect as compared to the treatment effect observed with either component of the combination used alone;• a treatment effect which is synergistic (i.e. super-additive) as compared to the treatment effect observed with either component of the combination used alone;• increased inhibition of tumor growth as compared to inhibition of tumor growth by either component of the combination used alone;• inhibition of tumor growth which is synergistic (i.e. super-additive) as compared to inhibition of tumor growth by either component of the combination used alone;• greater reduction in the number / activity of suppressor immune cells as compared to reduction of the number / activity of suppressor immune cells by either component of the combination used alone;• reduction in the number / activity of suppressor immune cells which is synergistic (i.e. superadditive) as compared to reduction of the number / activity of suppressor immune cells by either component of the combination used alone;• greater reduction of proliferation of suppressor immune cells as compared to reduction proliferation of suppressor immune cells by either component of the combination used alone• reduction of proliferation of suppressor immune cells which is synergistic (i.e. super-additive) as compared to reduction proliferation of suppressor immune cells by either component of the combination used alone;• greater reduction in the proportion of suppressor immune cells within a population of cells (e.g. CD45+ cells, e.g. CD45+ cells obtained from a tumor) as compared to the reduction of the proportion of suppressor immune cells by either component of the combination used alone; and• reduction in the proportion of suppressor immune cells within a population of cells (e.g. CD45+ cells, e.g. CD45+ cells obtained from a tumor) which is synergistic (i.e. superadditive) as compared to the reduction of the proportion of suppressor immune cells by either component of the combination used alone.• greater increase in the number and / or proportion and / or activity of antigen-specific CD8+ T cells as compared to the increase in the number and / or proportion and / or activity of antigenspecific CD8+ T cells by either component of the combination used alone;• increase in the number and / or proportion and / or activity of antigen-specific CD8+ T cells which is synergistic ( / .e. super-additive) as compared to the increase in the number and / or proportion and / or activity of antigen-specific CD8+ T cells by either component of the combination used alone;• greater reduction in the level of T cell exhaustion as compared to reduction in the level of T cell exhaustion by either component of the combination used alone;• reduction in the level of T cell exhaustion which is synergistic ( / .e. super-additive) as compared to reduction in the level of T cell exhaustion by either component of the combination used alone.Chemotherapy and radiotherapy respectively refer to treatment of a cancer with a drug or with ionising radiation (e.g. radiotherapy using X-rays or y-rays). The drug may be a chemical entity, e.g. small molecule pharmaceutical, antibiotic, DNA intercalator, protein inhibitor (e.g. kinase inhibitor), or a biological agent, e.g. antibody, antibody fragment, aptamer, nucleic acid (e.g. DNA, RNA), peptide, polypeptide, or protein. The drug may be formulated as a pharmaceutical composition or medicament. The formulation may comprise one or more drugs (e.g. one or more active agents) together with one or more pharmaceutically acceptable diluents, excipients or carriers.A treatment may involve administration of more than one drug. A drug may be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated. For example, the chemotherapy may be a co-therapy involving administration of two drugs, one or more of which may be intended to treat the cancer.The chemotherapy may be administered by one or more routes of administration, e.g. parenteral, intravenous injection, oral, subcutaneous, intradermal or intratumoral.The chemotherapy may be administered according to a treatment regime. The treatment regime may be a pre-determined timetable, plan, scheme or schedule of chemotherapy administration which may be prepared by a physician or medical practitioner and may be tailored to suit the patient requiring treatment. The treatment regime may indicate one or more of: the type of chemotherapy to administer to the patient; the dose of each drug or radiation; the time interval between administrations; the length of each treatment; the number and nature of any treatment holidays, if any etc. For a co-therapy a single treatment regime may be provided which indicates how each drug is to be administered.Chemotherapeutic drugs may be selected from: Abemaciclib, Abiraterone Acetate, Abitrexate (Methotrexate), Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation), ABVD, ABVE, ABVE- PC, AC, Acalabrutinib, AC-T, Adcetris (Brentuximab Vedotin), ADE, Ado-Trastuzumab Emtansine, Adriamycin (Doxorubicin Hydrochloride), Afatinib Dimaleate, Afinitor (Everolimus), Akynzeo (Netupitant and Palonosetron Hydrochloride), Aldara (Imiquimod), Aldesleukin, Alecensa (Alectinib), Alectinib,Alemtuzumab, Alimta (Pemetrexed Disodium), Aliqopa (Copanlisib Hydrochloride), Alkeran for Injection (Melphalan Hydrochloride), Alkeran Tablets (Melphalan), Aloxi (Palonosetron Hydrochloride), Alunbrig (Brigatinib), Ambochlorin (Chlorambucil), Amboclorin (Chlorambucil), Amifostine, Aminolevulinic Acid, Anastrozole, Aprepitant, Aredia (Pamidronate Disodium), Arimidex (Anastrozole), Aromasin (Exemestane), Arranon (Nelarabine), Arsenic Trioxide, Arzerra (Ofatumumab), Asparaginase Erwinia chrysanthemi, Atezolizumab, Avastin (Bevacizumab), Avelumab, Axicabtagene Ciloleucel, Axitinib, Azacitidine, Bavencio (Avelumab), BEACOPP, Becenum (Carmustine), Beleodaq (Belinostat), Belinostat, Bendamustine Hydrochloride, BEP, Besponsa (Inotuzumab Ozogamicin) , Bevacizumab, Bexarotene, Bexxar (Tositumomab and Iodine I 131 Tositumomab), Bicalutamide, BiCNU (Carmustine), Bleomycin, Blinatumomab, Blincyto (Blinatumomab), Bortezomib, Bosulif (Bosutinib), Bosutinib, Brentuximab Vedotin, Brigatinib, BuMel, Busulfan, Busulfex (Busulfan), Cabazitaxel, Cabometyx (Cabozantinib-S- Malate), Cabozantinib-S-Malate, CAF, Calquence (Acalabrutinib), Campath (Alemtuzumab), Camptosar (Irinotecan Hydrochloride), Capecitabine, CAPOX, Carac (Fluorouracil-Topical), Carboplatin, CARBOPLATIN-TAXOL, Carfilzomib, Carmubris (Carmustine), Carmustine, Carmustine Implant, Casodex (Bicalutamide), CEM, Ceritinib, Cerubidine (Daunorubicin Hydrochloride), Cervarix (Recombinant HPV Bivalent Vaccine), Cetuximab, CEV, Chlorambucil, CHLORAMBUCIL-PREDNISONE, CHOP, Cisplatin, Cladribine, Clafen (Cyclophosphamide), Clofarabine, Clofarex (Clofarabine), Clolar (Clofarabine), CMF, Cobimetinib, Cometriq (Cabozantinib-S-Malate), Copanlisib Hydrochloride, COPDAC, COPP, COPP-ABV, Cosmegen (Dactinomycin), Cotellic (Cobimetinib), Crizotinib, CVP, Cyclophosphamide, Cyfos (Ifosfamide), Cyramza (Ramucirumab), Cytarabine, Cytarabine Liposome, Cytosar-U (Cytarabine), Cytoxan (Cyclophosphamide), Dabrafenib, Dacarbazine, Dacogen (Decitabine), Dactinomycin, Daratumumab, Darzalex (Daratumumab), Dasatinib, Daunorubicin Hydrochloride, Daunorubicin Hydrochloride and Cytarabine Liposome, Decitabine, Defibrotide Sodium, Defitelio (Defibrotide Sodium), Degarelix, Denileukin Diftitox, Denosumab, DepoCyt (Cytarabine Liposome), Dexamethasone, Dexrazoxane Hydrochloride, Dinutuximab, Docetaxel, Doxil (Doxorubicin Hydrochloride Liposome), Doxorubicin Hydrochloride, Doxorubicin Hydrochloride Liposome, Dox-SL (Doxorubicin Hydrochloride Liposome), DTIC-Dome (Dacarbazine), Durvalumab, Efudex (Fluorouracil-Topical), Elitek (Rasburicase), Ellence (Epirubicin Hydrochloride), Elotuzumab, Eloxatin (Oxaliplatin), Eltrombopag Olamine, Emend (Aprepitant), Empliciti (Elotuzumab), Enasidenib Mesylate, Enzalutamide, Epirubicin Hydrochloride, EPOCH, Erbitux (Cetuximab), Eribulin Mesylate, Erivedge (Vismodegib), Erlotinib Hydrochloride, Erwinaze (Asparaginase Erwinia chrysanthemi), Ethyol (Amifostine), Etopophos (Etoposide Phosphate), Etoposide, Etoposide Phosphate, Evacet (Doxorubicin Hydrochloride Liposome), Everolimus, Evista (Raloxifene Hydrochloride), Evomela (Melphalan Hydrochloride), Exemestane, 5-FU (Fluorouracil Injection), 5-FU (Fluorouracil-Topical), Fareston (Toremifene), Farydak (Panobinostat), Faslodex (Fulvestrant), FEC, Femara (Letrozole), Filgrastim, Fludara (Fludarabine Phosphate), Fludarabine Phosphate, Fluoroplex (Fluorouracil-Topical), Fluorouracil Injection, Fluorouracil-Topical, Flutamide, Folex (Methotrexate), Folex PFS (Methotrexate), FOLFIRI, FOLFIRI-BEVACIZUMAB, FOLFIRI-CETUXIMAB, FOLFIRINOX, FOLFOX, Folotyn (Pralatrexate), FU-LV, Fulvestrant, Gardasil (Recombinant HPV Quadrivalent Vaccine), Gardasil 9 (Recombinant HPV Nonavalent Vaccine), Gazyva (Obinutuzumab), Gefitinib, Gemcitabine Hydrochloride, GEMCITABINE-CISPLATIN, GEMCITABINEOXALIPLATIN, Gemtuzumab Ozogamicin, Gemzar (Gemcitabine Hydrochloride), Gilotrif (Afatinib Dimaleate), Gleevec (Imatinib Mesylate), Gliadel (Carmustine Implant), Gliadel wafer (CarmustineImplant), Glucarpidase, Goserelin Acetate, Halaven (Eribulin Mesylate), Hemangeol (Propranolol Hydrochloride), Herceptin (Trastuzumab), HPV Bivalent Vaccine, Recombinant, HPV Nonavalent Vaccine, Recombinant, HPV Quadrivalent Vaccine, Recombinant, Hycamtin (Topotecan Hydrochloride), Hydrea (Hydroxyurea), Hydroxyurea, Hyper-CVAD, Ibrance (Palbociclib), Ibritumomab Tiuxetan, Ibrutinib, ICE, Iclusig (Ponatinib Hydrochloride), Idamycin (Idarubicin Hydrochloride), Idarubicin Hydrochloride, Idelalisib, Idhifa (Enasidenib Mesylate), Ifex (Ifosfamide), Ifosfamide, Ifosfamidum (Ifosfamide), IL-2 (Aldesleukin), Imatinib Mesylate, Imbruvica (Ibrutinib), Imfinzi (Durvalumab), Imiquimod, Imlygic (Talimogene Laherparepvec), Inlyta (Axitinib), Inotuzumab Ozogamicin, Interferon Alfa-2b, Recombinant, lnterleukin-2 (Aldesleukin), Intron A (Recombinant Interferon Alfa-2b), Iodine I 131 Tositumomab and Tositumomab, Ipilimumab, Iressa (Gefitinib), Irinotecan Hydrochloride, Irinotecan Hydrochloride Liposome, Istodax (Romidepsin), Ixabepilone, Ixazomib Citrate, Ixempra (Ixabepilone), Jakafi (Ruxolitinib Phosphate), JEB, Jevtana (Cabazitaxel), Kadcyla (Ado-Trastuzumab Emtansine), Keoxifene (Raloxifene Hydrochloride), Kepivance (Palifermin), Keytruda (Pembrolizumab), Kisqali (Ribociclib), Kymriah (Tisagenlecleucel), Kyprolis (Carfilzomib), Lanreotide Acetate, Lapatinib Ditosylate, Lartruvo (Olaratumab), Lenalidomide, Lenvatinib Mesylate, Lenvima (Lenvatinib Mesylate), Letrozole, Leucovorin Calcium, Leukeran (Chlorambucil), Leuprolide Acetate, Leustatin (Cladribine), Levulan (Aminolevulinic Acid), Linfolizin (Chlorambucil), LipoDox (Doxorubicin Hydrochloride Liposome), Lomustine, Lonsurf (Trifluridine and Tipiracil Hydrochloride), Lupron (Leuprolide Acetate), Lupron Depot (Leuprolide Acetate), Lupron Depot-Ped (Leuprolide Acetate), Lynparza (Olaparib), Marqibo (Vincristine Sulfate Liposome), Matulane (Procarbazine Hydrochloride), Mechlorethamine Hydrochloride, Megestrol Acetate, Mekinist (Trametinib), Melphalan, Melphalan Hydrochloride, Mercaptopurine, Mesna, Mesnex (Mesna), Methazolastone (Temozolomide), Methotrexate, Methotrexate LPF (Methotrexate), Methylnaltrexone Bromide, Mexate (Methotrexate), Mexate-AQ (Methotrexate), Midostaurin, Mitomycin C, Mitoxantrone Hydrochloride, Mitozytrex (Mitomycin C), MOPP, Mozobil (Plerixafor), Mustargen (Mechlorethamine Hydrochloride), Mutamycin (Mitomycin C), Myleran (Busulfan), Mylosar (Azacitidine), Mylotarg (Gemtuzumab Ozogamicin), Nanoparticle Paclitaxel (Paclitaxel Albumin-stabilized Nanoparticle Formulation), Navelbine (Vinorelbine Tartrate), Necitumumab, Nelarabine, Neosar (Cyclophosphamide), Neratinib Maleate, Nerlynx (Neratinib Maleate), Netupitant and Palonosetron Hydrochloride, Neulasta (Pegfilgrastim), Neupogen (Filgrastim), Nexavar (Sorafenib Tosylate), Nilandron (Nilutamide), Nilotinib, Nilutamide, Ninlaro (Ixazomib Citrate), Niraparib Tosylate Monohydrate, Nivolumab, Nolvadex (Tamoxifen Citrate), Nplate (Romiplostim), Obinutuzumab, Odomzo (Sonidegib), OEPA, Ofatumumab, OFF, Olaparib, Olaratumab, Omacetaxine Mepesuccinate, Oncaspar (Pegaspargase), Ondansetron Hydrochloride, Onivyde (Irinotecan Hydrochloride Liposome), Ontak (Denileukin Diftitox), Opdivo (Nivolumab), OPPA, Osimertinib, Oxaliplatin, Paclitaxel, Paclitaxel Albumin-stabilized Nanoparticle Formulation, PAD, Palbociclib, Palifermin, Palonosetron Hydrochloride, Palonosetron Hydrochloride and Netupitant, Pamidronate Disodium, Panitumumab, Panobinostat, Paraplat (Carboplatin), Paraplatin (Carboplatin), Pazopanib Hydrochloride, PCV, PEB, Pegaspargase, Pegfilgrastim, Peginterferon Alfa-2b, PEG-lntron (Peginterferon Alfa-2b), Pembrolizumab, Pemetrexed Disodium, Perjeta (Pertuzumab), Pertuzumab, Platinol (Cisplatin), Platinol-AQ (Cisplatin), Plerixafor, Pomalidomide, Pomalyst (Pomalidomide), Ponatinib Hydrochloride, Portrazza (Necitumumab), Pralatrexate, Prednisone, Procarbazine Hydrochloride, Proleukin (Aldesleukin), Prolia (Denosumab), Promacta (Eltrombopag Olamine), Propranolol Hydrochloride, Provenge (Sipuleucel-T), Purinethol (Mercaptopurine), Purixan(Mercaptopurine), [No Entries], Radium 223 Dichloride, Raloxifene Hydrochloride, Ramucirumab, Rasburicase, R-CHOP, R-CVP, Recombinant Human Papillomavirus (HPV) Bivalent Vaccine, Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine, Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine, Recombinant Interferon Alfa-2b, Regorafenib, Relistor (Methylnaltrexone Bromide), R-EPOCH, Revlimid (Lenalidomide), Rheumatrex (Methotrexate), Ribociclib, R-ICE, Rituxan (Rituximab), Rituxan Hycela (Rituximab and Hyaluronidase Human), Rituximab, Rituximab and Hyaluronidase Human, Rolapitant Hydrochloride, Romidepsin, Romiplostim, Rubidomycin (Daunorubicin Hydrochloride), Rubraca (Rucaparib Camsylate), Rucaparib Camsylate, Ruxolitinib Phosphate, Rydapt (Midostaurin), Sclerosol Intrapleural Aerosol (Talc), Siltuximab, Sipuleucel-T, Somatuline Depot (Lanreotide Acetate), Sonidegib, Sorafenib Tosylate, Sprycel (Dasatinib), STANFORD V, Sterile Talc Powder (Talc), Steritalc (Talc), Stivarga (Regorafenib), Sunitinib Malate, Sutent (Sunitinib Malate), Sylatron (Peginterferon Alfa-2b), Sylvant (Siltuximab), Synribo (Omacetaxine Mepesuccinate), Tabloid (Thioguanine), TAG, Tafinlar (Dabrafenib), Tagrisso (Osimertinib), Talc, Talimogene Laherparepvec, Tamoxifen Citrate, Tarabine PFS (Cytarabine), Tarceva (Erlotinib Hydrochloride), Targretin (Bexarotene), Tasigna (Nilotinib), Taxol (Paclitaxel), Taxotere (Docetaxel), Tecentriq (Atezolizumab), Temodar (Temozolomide), Temozolomide, Temsirolimus, Thalidomide, Thalomid (Thalidomide), Thioguanine, Thiotepa, Tisagenlecleucel, Tolak (Fluorouracil-Topical), Topotecan Hydrochloride, Toremifene, Torisel (Temsirolimus), Tositumomab and Iodine I 131 Tositumomab, Totect (Dexrazoxane Hydrochloride), TPF, Trabectedin, Trametinib, Trastuzumab, Treanda (Bendamustine Hydrochloride), Trifluridine and Tipiracil Hydrochloride, Trisenox (Arsenic Trioxide), Tykerb (Lapatinib Ditosylate), Unituxin (Dinutuximab), Uridine Triacetate, VAC, Valrubicin, Valstar (Valrubicin), Vandetanib, VAMP, Varubi (Rolapitant Hydrochloride), Vectibix (Panitumumab), VelP, Velban (Vinblastine Sulfate), Velcade (Bortezomib), Velsar (Vinblastine Sulfate), Vemurafenib, Venclexta (Venetoclax), Venetoclax, Verzenio (Abemaciclib), Viadur (Leuprolide Acetate), Vidaza (Azacitidine), Vinblastine Sulfate, Vincasar PFS (Vincristine Sulfate), Vincristine Sulfate, Vincristine Sulfate Liposome, Vinorelbine Tartrate, VIP, Vismodegib, Vistogard (Uridine Triacetate), Voraxaze (Glucarpidase), Vorinostat, Votrient (Pazopanib Hydrochloride), Vyxeos (Daunorubicin Hydrochloride and Cytarabine Liposome), Wellcovorin (Leucovorin Calcium), Xalkori (Crizotinib), Xeloda (Capecitabine), XELIRI, XELOX, Xgeva (Denosumab), Xofigo (Radium 223 Dichloride), Xtandi (Enzalutamide), Yervoy (Ipilimumab), Yescarta (Axicabtagene Ciloleucel), Yondelis (Trabectedin), Zaltrap (Ziv-Aflibercept), Zarxio (Filgrastim), Zejula (Niraparib Tosylate Monohydrate), Zelboraf (Vemurafenib), Zevalin (Ibritumomab Tiuxetan), Zinecard (Dexrazoxane Hydrochloride), Ziv-Aflibercept, Zofran (Ondansetron Hydrochloride), Zoladex (Goserelin Acetate), Zoledronic Acid, Zolinza (Vorinostat), Zometa (Zoledronic Acid), Zydelig (Idelalisib), Zykadia (Ceritinib) and Zytiga (Abiraterone Acetate).Multiple doses of the antigen-binding molecule, polypeptide, CAR, nucleic acid (or plurality thereof), expression vector (or plurality thereof), cell or composition may be provided. One or more, or each, of the doses may be accompanied by simultaneous or sequential administration of another therapeutic agent.Multiple doses may be separated by a predetermined time interval, which may be selected to be one of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days, or 1 , 2, 3, 4, 5, or 6 months. By way of example, doses may be given once every 7, 14, 21 or 28 days (plus or minus 3, 2, or 1 days).Methods of detectionThe invention also provides the articles of the present invention for use in methods for detecting, localizing or imaging VISTA, or cells expressing VISTA (e.g. MDSCs). The antigen-binding molecules described herein may be used in methods that involve the antigen-binding molecule to VISTA. Such methods may involve detection of the bound complex of the antigen-binding molecule and VISTA.In particular, detection of VISTA may be useful in methods of diagnosing / prognosing a disease / condition in which cells expressing VISTA (e.g. MDSCs) are pathologically implicated, identifying subjects at risk of developing such diseases / conditions, and / or may be useful in methods of predicting a subject’s response to a therapeutic intervention.As such, a method is provided, comprising contacting a sample containing, or suspected to contain, VISTA with an antigen-binding molecule as described herein, and detecting the formation of a complex of the antigen-binding molecule and VISTA. Also provided is a method comprising contacting a sample containing, or suspected to contain, a cell expressing VISTA with an antigen-binding molecule as described herein and detecting the formation of a complex of the antigen-binding molecule and a cell expressing VISTA.A sample may be taken from any tissue or bodily fluid. The sample may comprise or may be derived from: a quantity of blood; a quantity of serum derived from the individual’s blood which may comprise the fluid portion of the blood obtained after removal of the fibrin clot and blood cells; a tissue sample or biopsy; pleural fluid; cerebrospinal fluid (CSF); or cells isolated from said individual. In some embodiments, the sample may be obtained or derived from a tissue or tissues which are affected by the disease / condition (e.g. tissue or tissues in which symptoms of the disease manifest, or which are involved in the pathogenesis of the disease / condition).Suitable method formats are well known in the art, including immunoassays such as sandwich assays, e.g. ELISA. The methods may involve labelling the antigen-binding molecule, or target(s), or both, with a detectable moiety, e.g. a fluorescent label, phosphorescent label, luminescent label, immuno-detectable label, radiolabel, chemical, nucleic acid or enzymatic label as described herein. Detection techniques are well known to those of skill in the art and can be selected to correspond with the labelling agent.Methods comprising detecting VISTA, or cells expressing VISTA, include methods for diagnosing / prognosing a disease / condition described herein. Methods of this kind may be performed in vitro on a patient sample, or following processing of a patient sample. Once the sample is collected, the patient is not required to be present for the in vitro method to be performed, and therefore the method may be one which is not practised on the human or animal body. In some embodiments, the method is performed in vivo.Such methods may involve detecting or quantifying VISTA and / or cells expressing VISTA, e.g. in a patient sample. Where the method comprises quantifying the relevant factor, the method may further comprise comparing the determined amount against a standard or reference value as part of the diagnostic or prognostic evaluation. Other diagnostic / prognostic tests may be used in conjunction with those described herein to enhance the accuracy of the diagnosis or prognosis or to confirm a result obtained by using the tests described herein.Detection in a sample may be used for the purpose of diagnosis of a disease / condition (e.g. a cancer), predisposition to a disease / condition, or for providing a prognosis (prognosticating) for a disease / condition, e.g. a disease / condition described herein. The diagnosis or prognosis may relate to an existing (previously diagnosed) disease / condition.A subject may be selected for diagnostic / prognostic evaluation based on the presence of symptoms indicative of a disease / condition described herein, or based on the subject being considered to be at risk of developing a disease / condition described herein.The present disclosure also provides methods for selecting / stratifying a subject for treatment with a VISTA-targeted agent. In some embodiments a subject is selected for treatment / prevention in accordance with the methods of the present disclosure, or is identified as a subject which would benefit from such treatment / prevention, based on detection / quantification of VISTA, or cells expressing VISTA, e.g. in a sample obtained from the individual.SubjectsThe subject in accordance with aspects described herein may be any animal or human. The subject is preferably mammalian, more preferably human. The subject may be a non-human mammal, but is more preferably human. The subject may be male or female. The subject may be a patient. A subject may have been diagnosed with a disease or condition requiring treatment (e.g. a cancer, e.g. a cancer described herein), may be suspected of having such a disease / condition, or may be at risk of developing / contracting such a disease / condition.In some embodiments, the subject to be treated according to a therapeutic or prophylactic method of the present disclosure herein is a subject having, or at risk of developing, a cancer, e.g. a cancer described herein. In embodiments according to the present disclosure, a subject may be selected for treatment according to the methods based on characterisation for certain markers of such disease / condition.In some embodiments, a patient may be selected for treatment described herein based on the detection of a cancer or cells expressing / overexpressing VISTA, e.g. in a sample obtained from the subject (e.g. a biopsy, e.g. of a tumor).KitsThe present disclosure also provides kits of parts. A kit according to the present disclosure may comprise components for performing a method described herein, in whole or in part.The kit may have at least one container having a predetermined quantity of an antigen-binding molecule or composition described herein.In some aspects of the present disclosure a kit of parts is provided. In some embodiments, the kit may comprise an antigen-binding molecule, polypeptide, CAR, ADC, nucleic acid (or plurality thereof), expression vector (or plurality thereof), cell (or plurality thereof), or composition described herein, and which may be provided in a predetermined quantity.The kit may provide an antigen-binding molecule or composition described herein together with instructions for administration to a patient in order to treat a specified disease / condition (e.g. a disease / condition described herein, e.g. a cancer).The kit may provide a polypeptide complex comprising an antigen-binding moiety that binds to VISTA according to the disclosure, and a linker-payload moiety (e.g. according to the present disclosure). The kit may further comprise reagents for conjugating the antigen-binding polypeptide complex and the linkerpayload moiety.The kit may further comprise reagents, buffers and / or standards required for execution of a method according to the present disclosure. Kits according to the present disclosure may include instructions for use, e.g. in the form of an instruction booklet or leaflet. The instructions may include a protocol for performing any one or more of the methods described herein.Sequence identityAs used herein, ‘sequence identity’ refers to the percent of nucleotides / amino acid residues in a subject sequence that are identical to nucleotides / amino acid residues in a reference sequence, after aligning the sequences and, if necessary, introducing gaps, to achieve the maximum percent sequence identity between the sequences. Pairwise and multiple sequence alignment for the purposes of determining percent sequence identity between two or more amino acid or nucleic acid sequences can be achieved in various ways known to a person of skill in the art, for instance, using publicly available computer software such as ClustalOmega (Sdding, J. 2005, Bioinformatics 21 , 951-960), T-coffee (Notredame et a / . 2000, J. Mol. Biol. (2000) 302, 205-217), Kalign (Lassmann and Sonnhammer 2005, BMC Bioinformatics, 6(298)) and MAFFT (Katoh and Standley 2013, Molecular Biology and Evolution, 30(4) 772-780) software. When using such software, the default parameters, e.g. for gap penalty and extension penalty, are preferably used.SequencesTable ATable BTable CTable DThe present disclosure includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.Aspects and embodiments of the present disclosure will now be illustrated, by way of example, with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.Throughout this specification, including the claims which follow, unless the context requires otherwise, the word ‘comprise,’ and variations such as ‘comprises’ and ‘comprising,’ will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.It must be noted that, as used in the specification and the appended claims, the singular forms ‘a’, ‘an’, and ‘the’ include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from ‘about’ one particular value, and / or to ‘about’ another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent ‘about’, it will be understood that the particular value forms another embodiment.Where a nucleic acid sequence is disclosed or referred to herein, the reverse complement thereof is also expressly contemplated.Methods described herein may preferably be performed in vitro. The term ‘in vitro’ is intended to encompass procedures performed with cells in culture whereas the term ‘in vivo’ is intended to encompass procedures with / on intact multi-cellular organisms.Values may be expressed herein as ‘about’ a particular value. Similarly, ranges may be expressed herein as from ‘about’ a particular value, and / or to ‘about’ another particular value. The term ‘about’ in relation to a numerical value is optional, and means for example + / - 10 %. By way of illustration, reference e.g. to ‘about 10 %’ is to be construed as 9 % to 11 %. In instances herein where ‘about’ is recited, the value it precedes is also specifically contemplated. By way of illustration, reference e.g. to ‘about 10 %’ also specifically contemplates 10 %.Brief Description of the FiguresEmbodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures.Figures 1 A and 1 B. Graph showing binding affinity of anti-VISTA antibody variants (LD1 -6) for human VISTA measured by ELISA (Figure 1A). Each variant has different single amino acid substitutions compared with parental clone V9-4K, and the amino acid substitutions employed to remove developability risks are shown in Figure 1 B. The ECso values measured by ELISA are shown in Figure 1 B.Figures 2A, 2B and 2C. Graphs showing binding affinities of anti-VISTA antibody variants V9- 4K_FLD3, V9-4K_FLD4, V9-4K_FLD5 and V9-4K_FLD6 for human VISTA measured by ELISA,compared with parental clone V9-4K (Figures 2A and 2B). Amino acid substitutions in the anti-VISTA antibody variants and measured binding affinities (EC50 values) are indicated in Figure 20.Figures 3A, 3B and 3C. Graphs and table showing antibody binding measured by flow cytometry. Figures 3A and 30 show the binding affinity of anti-VISTA antibody variants V9-4K_FLD4, V9-4K_FLD5 and V9-4K_FLD6 for human VISTA overexpressed on CHO-K1 cells, compared with parental clone V9- 4K, and Figure 3B shows non-specific binding of the antibodies to non-transfected CHO-K1 cells. The curves were generated by averaging the MFI values at each antibody concentration and were derived from two independent experiments.Figure 4. Table showing the expression yield and purity of antibodies V9-4K_FLD3, V9-4K_FLD4, V9-4K_FLD5 and V9-4K_FLD6, compared with parental clone V9-4K.Figures 5A and 5B. Graphs and tables showing cross-species antibody binding measured by ELISA for V9-4K (5A) and 9M2-C12 (“HMBD-V9”) (5B). The EC50 values measured by ELISA are shown in the tables.Figure 6. Graph and table showing the results of analysis of the ability of V9-4K h IgG 1 to inhibit interaction between VISTA and VSIG3, as determined by competition ELISA (data shown are mean of n=3 measurements and error bars are SEM).Figure 7. Graph and table showing the results of analysis of the ability of V9-4K h IgG 1 to inhibit interaction between VISTA and LRIG1 , as determined by competition ELISA (data shown are mean of n=3 measurements and error bars are SEM).Figure 8. Graph and table showing the results of analysis of the ability of V9-4K h IgG 1 to inhibit interaction between VISTA and PSGL1 , as determined by competition ELISA (data shown are mean of n=3 measurements and error bars are SEM).Figures 9A, 9B, 9C and 9D. Fluorescence images of APC-labelled V9-4K incubated with human monocytes and human neutrophils at 37 °C for 0.5, 2 and 6 h to measure internalization. Trafficking was detected in the endosomes of monocytes (9A), the lysosomes of monocytes (9B), the endosomes of neutrophils (90), and the lysosomes of neutrophils (9D).Figures 10A and 10B. Graphs showing inhibition of proliferation of different HEK293T cells expressing VISTA (10A) and wild-type HEK293T cells (10B). Data shown are mean of n=3 measurements and error bars are SEM.ExamplesExample 1 : Anti-VISTA antibodiesAnti-VISTA antibody clone V9-4K was modified to contain substitutions in the CDRs and FW regions to improve properties, e.g. stability, oxidation, isomerization, expression, purity. Antibodies LD1 to LD6containing single modifications (see Figure 1 B) were produced and analyzed. New antibodies V9- 4K_FLD3, V9-4K_FLD4, V9-4K_FLD5 and V9-4K_FLD6 were produced, containing combinations of modifications from LD1 to LD6 (see Figure 20, and Tables A-D for sequences of V9-4K_FLD3 to V9- 4K_FLD6).ELISA was used to determine the binding affinities of the antibodies. Anti-VISTA antibodies were analysed for binding to human VISTA protein.Figures 2A and 2B show that antibodies V9-4K_FLD3, V9-4K_FLD4, V9-4K_FLD5 and V9-4K_FLD6 retained affinity comparable to that of the parental V9-4K antibody. Figures 1A and 1 B show that similar modifications at the same positions did not always lead to retention of binding affinity - for example, the LD5 modification led to decreased affinity for VISTA.All FLD variants tested had expression yield and purity comparable to that of the parent V9-4K antibody (Figure 4).Example 2: Analysis of cell surface antigen-binding by flow cytometryBinding of selected antibodies to human VISTA expressed on cells were tested using flow cytometry.CH0-K1 cells (which do not express high levels of VISTA) were transfected with vector encoding human VISTA (i.e. CHOK1_OE-huB7B5 cells). Transfected and non-transfected cells were plated at 0.03 x 106cells per well and incubated with 50 pL anti-VISTA antibody or isotype control antibody (N297A isotype) at 4°C for 45 minutes. Serial dilutions of the primary antibody, starting from 10 pg / mL, were used.The cells were washed twice with FACS buffer (PBS with 5mM EDTA and 0.5% BSA) and incubated with goat anti-Human IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (Invitrogen, #A21445) (1 :1000) for 20 min at 4°C. The cells were washed twice and resuspended in 45 pL of FACS / DAPI buffer (1 :400) for flow cytometric analysis using iQue3 (Sartorius). After acquisition, all raw data were analyzed using Flowlogic software. Cells were gated using forward and side scatter profile and Median of Fluorescence Intensity (MFI) value was determined for native and overexpressing cell populations.The results are shown in Figures 3A, 3B and 3C. The anti-VISTA antibodies were shown to bind to human VISTA with high specificity, as no non-specific binding to non-transfected cells was observed (Figures 3A and 3B). V9-4K_FLD5 retained binding comparable to that of parent antibody V9-4K, while V9-4K_FLD4 and V9-4K_FLD6 have slightly lower binding affinity (Figures 3A and 3C).Example 3: Analysis of cross-species binding of anti-VISTA antibodyELISA was used to determine cross-species binding of the anti-VISTA antibody V9-4K and mouse anti- VISTA antibody 9M2-C12 (“HMBD-V9”). V9-4K is a humanized clone of 9M2-C12. The anti-VISTA antibodies were analyzed for binding to human VISTA protein, rhesus VISTA protein, cynomolgus VISTA protein, mouse VISTA protein and rat VISTA protein. His-tagged proteins were obtained from SinoBiological, product codes #13482-H08H, #13482-H08H, #13482-H08H, #13482-H08H and #13482-H08H, respectively. Binding to human HER3 protein (irrelevant antigen, negative control) was also assessed (SinoBiological, #10201-H08H).Figure 5A demonstrates that anti-VISTA antibody V9-4K binds to human, cynomolgus macaque and rhesus macaque VISTA with high affinity, while the isotype control does not. The anti-VISTA antibody V9- 4K does not bind to rat VISTA and mouse VISTA. The mouse anti-VISTA antibody (HMBD-V9) from which V9-4K is derived also binds to human, cynomolgus macaque and rhesus macaque VISTA with high affinity (Figure 5B), albeit the affinity of V9-4K for each of human, cynomolgus and rhesus VISTA is higher than the affinity of the mouse anti-VISTA antibody.Example 4: Anti-VISTA antibody inhibits binding between VISTA and its ligandsThe ability of the parent anti-VISTA antibody V9-4K to inhibit the interaction of VISTA with its ligands VSIG3, LRIG1 and PSGL1 was assessed using ELISA-based protein binding assays.As explained hereinabove, key interaction partners of VISTA include V-Set and Immunoglobulin domain containing 3 (VSIG3), LRIG1 and PSGL1.The following antibodies were analyzed: anti-VISTA antibody V9-4K, an isotype control and an antibody that does not bind to VISTA. The ligands tested were human VSIG3-Fc recombinant protein (R&D Systems), human LRIG1-His recombinant protein (R&D Systems) and human PSGL1-His protein. Recombinant human VSIG3-Fc protein was biotinylated using a biotinylation kit (Invitrogen, #21455) as per the manufacturer’s protocol.384-well plates were coated with 5 pg / mL of human VISTA-Fc recombinant protein (R&D #7126-B7) diluted in PBS overnight at 4°C. After blocking with 1% BSA at room temperature and washing three times, plates were incubated with anti-VISTA V9-4K or isotype control for 1 hour at room temperature at 200 nM (30 pg / mL) to 2 pM (0.0003 pg / mL). After incubation and washing (3x), biotinylated recombinant human VSIG3-Fc, recombinant human PSGL1-His protein or recombinant human PSGL1-His protein was added at 1 pg / mL for 2 hours. For the PSGL1-His competition assay, the incubation was performed at acidic pH (pH 6). Post incubation, plates were washed three times with TBS-T and incubated with streptavidin HRP (R&D #DY998) antibody for 1 hour at room temperature followed by three further washes. The absorbance was measured at 450 nm using VICTOR Nivo plate reader. Background was accounted for by subtracting the optical density (OD) of wells with only blocking buffer and no sample (negative control) from OD of the wells with serially diluted test articles. Average and SEM were calculated by GraphPad PRISM 10, and Graph was plotted using GraphPad PRISM 10, fitting the data points to a three-parameter logistic model.Figure 6 shows that parent antibody V9-4K antagonises VISTA-VSIG3 interaction in a dose-dependent manner, with an IC50 of 3.069 nM.Similarly, Figure 7 shows that parent antibody V9-4K demonstrates a dose dependent inhibition of VISTA- LRIG1 binding, with a IC50 value of 2.252 nM.Figure 8 shows that parent antibody V9-4K can antagonise VISTA-PSGL1 interaction in a dosedependent manner, with an IC50 of 7.489 nM at acidic pH.The present data thus demonstrate that V9-4K neutralises the activity of VISTA by inhibiting binding to each of VSIG3, LRIG1 and PSGL1 . V9-4K-based antibodies that inhibit the VISTA-VSIG3, VISTA-LRIG1 and VISTA-PSGL1 interactions may be useful in tumor immunology and immunotherapy.Example 5: Internalization of anti-VISTA antibody (V9-4K) in human monocytes and neutrophilsThe inventors next tested the internalization properties of parent antibody V9-4K in human primary cells that express VISTA (monocytes and neutrophils). Internalization of an antibody is important in research of targeted drug delivery, especially with antibody-drug conjugates (ADCs). ADCs are engineered antibodies linked to a potent cytotoxic payload moiety, which can be trafficked to the lysosome for drug release and cell death.The anti-VISTA antibody V9-4K and isotype control (Ultra-LEAF™ Purified Human lgG1 Isotype Control recombinant Antibody, Biolegend, #403502) were conjugated to allophycocyanin (APC) using a conjugation kit (Abeam, #Ab201807) according to the manufacturer’s instructions. Fluorescence microscopy was performed on human monocytes and neutrophils treated with APC labelled-V9-4K.Figure 9A shows that parental antibody V9-4K is internalised into endosomes of human monocytes within 30 minutes, and Figure 9B shows that V9-4K is trafficked to lysosomes of human monocytes within 2 hours.In human neutrophils, parental antibody V9-4K is internalised within 2 hours (Figure 9C) and trafficked to lysosomes for up to 2 hours (Figure 9D).Thus, V9-4K is rapidly internalized in human monocytes and neutrophils.Experimental detailsIsolation of cellsWhole blood from three healthy donors was collected in EDTA tubes. Fresh polymorphonuclear neutrophils (PMNs) were isolated directly from 8 mL of whole blood using MACSxpress® Human Whole Blood Neutrophil Isolation Kit (Miltenyi, #130-104-434). Fresh monocytes were isolated from fresh peripheral blood mononuclear cells (PBMCs) using Classical Human Monocyte Isolation Kit (Miltenyi, #130-117-337). PBMCs were isolated from whole blood using SepMate tubes (Stemcell Technologies, #86450) and Lymphoprep (Stemcell Technologies, #07851). Residual red blood cells were lysed with equal volume of ACK lysing buffer (Lonza, #BP10-548E) for 5 min at RT. Samples were washed with PBS, if necessary few rounds of lysis were performed. Chambers in 12-well slides (Ibidi, #81201) were coated with Poly-D-lysin (Gibco, #A3890401) as per manufacturer instruction.AntibodiesRAB5A Monoclonal Antibody (Invitrogen, Cat # 2E8B11) was used to stain endosomes. FITC anti-human CD107a (LAMP-1) Antibody (Biolegend, Cat # 32806) was used to stain lysosomes. A goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (Invitrogen, Cat# A-11032) was used as a secondary antibody.Assay detailsThe Poly-D-lysin-coated chambers were washed with PBS and 1 x 105cells were plated in 100 of RPMI pl / well. The slides were placed on ice for 30 min and then treated with 1 pg / mL of APC conjugated anti- VISTA or isotype control antibody for 30 min, 2 h or 6 h at at 37°C. The control slide (representing 0 h) was incubated for 45 min on ice. Post-treatment, slides were fixed with 200 pl ice-cold 4% PFA, quenched with glycine and washed twice with ice-cold PBS. Permeabilization was performed with BP- staining buffer (0.4% Saponin, 1% BSA, 2% normal goat serum in PBS) for 1 h at RT. The slides were then washed and incubated with 100 pl of BP-staining buffer constituting primary antibody cocktail (5 pg / ml of RAB5A primary antibody for endosomal staining and 1 pg / ml of LAMP-1 for lysosomal staining) overnight. The slides were then incubated with the Alexa Fluor™ 594 Secondary Antibody at 2 pg / ml for 1 h at RT in BP-staining buffer, washed twice with PBS and incubated with DAPI staining solution (1 :100 in BP-staining buffer) for 30 min at RT. Silicon separators were gently removed, and the slides were left to airdry in the dark for 10 min. The slides were mounted using Prolonged Diamond mounting media (Invitrogen, #P36961) and kept overnight at 4 °C. The slides were subsequently imaged using Microscope Leica DMi8 using lasers 405, 488, 594 and 647. Images were analyzed using LAS X Software.Example 6: Characterization of an anti-VISTA antibody-drug conjugate in an in vitro cell killing assay An antibody-drug conjugate was prepared by conjugating the V9-4K parent antibody with a cytotoxic payload moiety (Exatecan) via a linker. The ability of the resulting V9-4K-cytotoxic payload ADC to induce cytotoxicity was assessed. An isotype-cytotoxic payload ADC and unconjugated V9-4K were used as negative controls.The cytotoxic payload moiety in the antibody-drug conjugates is Exatecan (DX-8951 ; DrugBank Acc. No. DB12185) which is a DNA topoisomerase I inhibitor derivative of camptothecin.The effect of V9-4K-cytotoxic payload ADC on cell viability was measured using a CellTiter-Glo® 2.0 Cell Viability Assay (Promega, Cat No G9241). HEK293T cells overexpressing human VISTA and nontransfected HEK293T cells were seeded at 10,000 cells per well in a 96-well flat bottom transparent plate, and incubated overnight. The ADCs and controls were added to the cells and incubated for 4 days at 37°C and 5% CO2. Serial dilutions were used starting from 50 pg / ml. On day 4 post-treatment, 50 pL of the CellTiter-Glo reagent was added to the plates and incubated for 25 mins with gentle shaking at 600 rpm. Cell viability was measured via luminescence using Victor Nivo plate reader (PerkinElmer). Background was subtracted using Luminescence values from wells having only media (without any cells). Percent inhibition was calculated using the formula 100- {(Lum of cells treated with drug / Lum of cellstreated with buffer control) *100}, Lum= Luminescence. Average and SEM was calculated by GraphPad PRISM 9 and the graphs were plotted using GraphPad PRISM 9 and fitting the data points to a four- parameter logistic model. The results are shown in Figures 10A and 10B. The V9-4K-cytotoxic payload ADC specifically kills HEK293T cells expressing human VISTA.

Claims

Claims:

1. An antigen-binding molecule, optionally isolated, comprising:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NO:42 or 70 HC-CDR3 having the amino acid sequence of SEQ ID NO:43 or 76; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .

2. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NO:42 HC-CDR3 having the amino acid sequence of SEQ ID NO:43; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .

3. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:71 or 76; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .

4. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:72; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .

895. The antigen-binding molecule according to claim 1 , wherein the antigen-binding molecule comprises:(i) a heavy chain variable (VH) region incorporating the following CDRs:HC-CDR1 having the amino acid sequence of SEQ ID NO:41 HC-CDR2 having the amino acid sequence of SEQ ID NQ:70 HC-CDR3 having the amino acid sequence of SEQ ID NO:73; and / or(ii) a light chain variable (VL) region incorporating the following CDRs:LC-CDR1 having the amino acid sequence of SEQ ID NO:49 LC-CDR2 having the amino acid sequence of SEQ ID NQ:50 LC-CDR3 having the amino acid sequence of SEQ ID NO:51 .

6. The antigen-binding molecule according to any one of claims 1 to 5, wherein the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs):HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:77HC-FR4 having the amino acid sequence of SEQ ID NQ:60.

7. The antigen-binding molecule according to any one of claims 1 to 6, wherein the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs):HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:59HC-FR4 having the amino acid sequence of SEQ ID NQ:60.

8. The antigen-binding molecule according to any one of claims 1 to 6, wherein the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs):HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:74HC-FR4 having the amino acid sequence of SEQ ID NQ:60.

9. The antigen-binding molecule according to any one of claims 1 to 6, wherein the antigen-binding molecule comprises: a VH region incorporating the following framework regions (FRs):HC-FR1 having the amino acid sequence of SEQ ID NO:57HC-FR2 having the amino acid sequence of SEQ ID NO:58HC-FR3 having the amino acid sequence of SEQ ID NO:75HC-FR4 having the amino acid sequence of SEQ ID NQ:60.

10. The antigen-binding molecule according to any one of claims 1 to 9, wherein the antigen-binding molecule comprises: a VL region incorporating the following framework regions (FRs):LC-FR1 having the amino acid sequence of SEQ ID NO:62LC-FR2 having the amino acid sequence of SEQ ID NO:63LC-FR3 having the amino acid sequence of SEQ ID NO:64LC-FR4 having the amino acid sequence of SEQ ID NO:65.11 . The antigen-binding molecule according to any one of claims 1 to 10, wherein the antigen-binding molecule comprises: a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:56, 66, 67, 68, or 69; and / or a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:61 .

12. An antigen-binding molecule comprising: a VH region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:99; and a VL region comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NQ:101 .

13. The antigen-binding molecule according to any one of claims 1 to 12, wherein the antigen-binding molecule comprises a heavy chain comprising an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:78 and comprises the substitutions L234A, L235A and P329A.

14. The antigen-binding molecule according to any one of claims 1 to 13, wherein the antigen-binding molecule comprises:(a) (i) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:84, 87, 90, 93, or 96; and / or(ii) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:98; or(b) (i) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NQ:100; and / or(ii) a polypeptide comprising, or consisting of, an amino acid sequence having at least 70% sequence identity to the amino acid sequence of SEQ ID NO:102.

15. An antibody-drug conjugate comprising an antigen-binding molecule according to any one of claims 1 to 14.

16. A nucleic acid, or a plurality of nucleic acids, optionally isolated, encoding an antigen-binding molecule according to any one of claims 1 to 14.

17. An expression vector, or a plurality of expression vectors, comprising a nucleic acid or a plurality of nucleic acids according to claim 16.

18. A composition comprising an antigen-binding molecule according to any one of claims 1 to 14, an antibody-drug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, or an expression vector or a plurality of expression vectors according to claim 17, optionally further comprising a pharmaceutically acceptable carrier, diluent, excipient or adjuvant.

19. A cell comprising an antigen-binding molecule according to any one of claims 1 to 14, an antibodydrug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, an expression vector or a plurality of expression vectors according to claim 17, or a composition according to claim 18.

20. An antigen-binding molecule according to any one of claims 1 to 14, an antibody-drug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, an expression vector or a plurality of expression vectors according to claim 17, a composition according to claim 18, or a cell according to claim 19, for use in a method of medical treatment or prophylaxis, or in a method of diagnosis or prognosis.21 . An antigen-binding molecule according to any one of claims 1 to 14, an antibody-drug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, an expression vector or a plurality of expression vectors according to claim 17, a composition according to claim 18, or a cell according to claim 19, for use in treating or preventing a cancer.

22. Use of an antigen-binding molecule according to any one of claims 1 to 14, an antibody-drug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, an expression vector or a plurality of expression vectors according to claim 17, a composition according to claim 18, or a cell according to claim 19, in the manufacture of a medicament for treating or preventing a cancer.

23. A method of treating or preventing a cancer, comprising administering to a subject a therapeutically- or prophylactically-effective amount of an antigen-binding molecule according to any one of claims 1 to 14, an antibody-drug conjugate according to claim 15, a nucleic acid or a plurality of nucleic acids according to claim 16, an expression vector or a plurality of expression vectors according to claim 17, a composition according to claim 18, or a cell according to claim 19.

24. The antigen-binding molecule, antibody-drug conjugate, nucleic acid, plurality of nucleic acids, expression vector, plurality of expression vectors, composition or cell for use according to claim 21 , the use according to claim 22, or the method according to claim 23, wherein the cancer is selected from: a cancer comprising cells expressing / overexpressing VISTA, a cancer comprising infiltration of cells expressing VISTA, a cancer characterised by the presence of cells expressing VISTA in the vicinityof / proximal to cells of the cancer, a cancer comprising a tumor displaying infiltration of cells expressing VISTA, a hematological cancer, a myeloid hematologic cancer, leukemia, T cell leukemia, B cell leukemia, acute myeloid leukemia, chronic myelomonocytic leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, lymphoma, B cell lymphoma, T cell lymphoma, multiple myeloma, mesothelioma, epithelioid mesothelioma, myelodysplastic syndrome, gliblastoma multiforme, brain lower grade glioma, sarcoma, testicular germ cell tumor, myeloproliferative disorder, a solid tumor, lung cancer, non-small cell lung cancer, gastric cancer, gastric carcinoma, colorectal cancer, colorectal carcinoma, colorectal adenocarcinoma, uterine cancer, uterine corpus endometrial carcinoma, breast cancer, triple negative breast cancer, triple negative breast invasive carcinoma, liver cancer, hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, thyroid cancer, thymoma, skin cancer, melanoma, cutaneous melanoma, kidney cancer, renal cell carcinoma, renal papillary cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, ovarian cancer, ovarian carcinoma, ovarian serous cystadenocarcinoma, prostate cancer and prostate adenocarcinoma.

25. An in vitro complex, optionally isolated, comprising an antigen-binding molecule according to any one of claims 1 to 14, or an antibody-drug conjugate according to claim 15, bound to VISTA.

26. A method comprising contacting a sample containing, or suspected to contain, VISTA with an antigenbinding molecule according to any one of claims 1 to 14, and detecting the formation of a complex of the antigen-binding molecule with VISTA.

27. A method of selecting or stratifying a subject for treatment with a VISTA-targeted agent, the method comprising contacting, in vitro, a sample from the subject with an antigen-binding molecule according to any one of claims 1 to 14 and detecting the formation of a complex of the antigen-binding molecule with VISTA.

28. Use of an antigen-binding molecule according to any one of claims 1 to 14 as an in vitro or in vivo diagnostic or prognostic agent.

Images