Anti-human vista antibodies and use thereof

Abstract

This invention provides antagonistic and agonistic anti-human VISTA antibodies and antibody fragments. These antagonistic antibodies and antibody fragments can be used to inhibit or block the suppressive effect of VISTA on T-cell immunity, thereby promoting T-cell immunity. These agonistic antibodies and antibody fragments can be used to enhance or mimic the suppressive effect of VISTA on T-cell immunity, thereby suppressing T-cell immunity. These antagonistic antibodies and antibody fragments are particularly suitable for treating cancer and infectious conditions. These agonistic antibodies and antibody fragments are particularly suitable for treating autoimmune diseases, allergies, inflammatory conditions, GVHD, sepsis, and transplant recipients. This invention also provides screening analyses for identifying these agonists.

Description

Anti-human VISTA antibodies and their uses This application claims the benefit of U.S. Provisional Application No. 62 / 323,193 filed April 15, 2016, U.S. Provisional Application No. 62 / 343,355 filed May 31, 2016, U.S. Provisional Application No. 62 / 372,362 filed August 9, 2016, U.S. Provisional Application No. 62 / 385,627 filed September 9, 2016, U.S. Provisional Application No. 62 / 425,184 filed November 22, 2016, and U.S. Provisional Application No. 62 / 425,185 filed July 19, 2016. U.S. Provisional Application No. 62 / 363,929 filed on July 21, 2016, U.S. Provisional Application No. 62 / 365,085 filed on July 21, 2016, U.S. Provisional Application No. 62 / 385,805 filed on September 9, 2016, U.S. Provisional Application No. 62 / 363,931 filed on July 19, 2016, U.S. Provisional Application No. 62 / 365,102 filed on July 21, 2016, U.S. Provisional Application No. 62 / 385,805 filed on September 9, 2016 No. 5,871, U.S. Provisional Application No. 62 / 363,917 filed on July 19, 2016, U.S. Provisional Application No. 62 / 365,081 filed on July 21, 2016, U.S. Provisional Application No. 62 / 385,888 filed on September 9, 2016, U.S. Provisional Application No. 62 / 364,073 filed on July 19, 2016, U.S. Provisional Application No. 62 / 365,166 filed on July 21, 2016, U.S. Provisional Application No. 62 / 366,081 filed on September 9, 2016

[0016] This application claims priority to U.S. Provisional Application Nos. 62 / 385,893, filed on July 19, 2016, 62 / 363,925, filed on July 19, 2016, 62 / 365,087, filed on July 21, 2016, 62 / 385,785, filed on September 9, 2016, and 62 / 406,632, filed on October 11, 2016, each of which is hereby incorporated by reference in its entirety. This application is related to PCT Application No. PCT / US2017 / 027800, "ANTI-HUMAN VISTA ANTIBODIES AND USE THEREOF," filed on April 14, 2017 (Attorney Docket No. 43260.2214), which is hereby incorporated by reference and also claims priority. The present invention relates to the identification of novel anti-human VISTA antibodies and antibody fragments, namely, anti-human VISTA (V-region containing immunoglobulin inhibitor of T cell activation (1)), ("VISTA") antibodies and antibody fragments. More specifically, the present application provides novel human VISTA agonists, namely, anti-human VISTA antibodies and antibody fragments that stimulate or promote the inhibitory effect of human VISTA on immunity, especially on T cell immunity. Furthermore, the present invention relates to the enhancement or simulation of the inhibitory effect of VISTA on immunity by such agonists, such as its effect on CD4 + or CD8 + T cell proliferation, CD4 + or CD8 + The present invention also relates to the use of agonist antibodies and antibody fragments as prophylactic or therapeutic agents, particularly in the treatment of conditions where preventing or suppressing T cell immunity and the expression of proinflammatory cytokines has therapeutic benefits (such as autoimmunity, inflammation, allergic disorders, sepsis, GVHD) or in alleviating inflammatory side effects of certain conditions (such as cancer). The present application also provides novel antagonists, that is, anti-human VISTA antibodies and antibody fragments that antagonize or inhibit the inhibitory effect of human VISTA on immunity, especially the effect of VISTA on T cell immunity. In addition, the present invention relates to the novel antagonists that block or inhibit the inhibitory effect of VISA on immunity, that is, their effect on CD4 + or CD8 + T cell proliferation, CD4 + or CD8 + The present invention also relates to the specific use of these antagonistic antibodies and antibody fragments as prophylactic or therapeutic agents, particularly in the treatment of conditions where promoting T cell immunity has therapeutic benefits, such as in the treatment of cancer and infectious diseases. Negative checkpoint regulator (NCR) pathways have been shown to be unique clinical targets for the treatment of human immune-related diseases. Blocking two NCRs (CTLA-4 and PD-1) with monoclonal antibodies (mAbs) to enhance tumor immunity is revolutionizing cancer treatment and has established these pathways as clinically effective targets in human disease. Soluble forms of NCR ligands that trigger NCR pathways have also entered the clinic as immunosuppressive drugs for the treatment of autoimmunity (e.g., AMP-110 / B7-H4-Ig for rheumatoid arthritis). VISTA (see reference 1) is an NCR ligand whose closest lineage relationship is PD-L1. VISTA shares homology with PD-L1 but displays a unique expression pattern that is restricted to the hematopoietic compartment. Specifically, VISTA is expressed on CD11b 高 It is constitutively and highly expressed on myeloid cells and on CD4 + and CD8 + VISTA is expressed at lower levels on T cells. Like PD-L1, VISTA is a highly immunosuppressive ligand (Reference 1), and like PD-L1, blocking VISTA allows therapeutic immunity to develop in preclinical tumor models of cancer (see Reference 2). However, blocking VISTA enhances immunity, especially CD8 + and CD4 + Treatment with a soluble Ig fusion protein of the extracellular domain of VISTA (VISTA-Ig) suppresses immunity and has been shown to prevent the development of autoimmune diseases in multiple murine models. Clear scientific evidence has shown that VISTA is a ligand that induces extreme T cell suppression. Various groups (including Dartmouth College and Jannsen) have reported a variety of antagonistic anti-human VISTA antibodies. These antibodies are suitable for treating conditions where it is necessary to suppress the immunosuppressive effect of VISTA on T cell immunity, such as cancer and infection. However, to the best of the inventor's knowledge, there have been no anti-human VISTA antibodies or antibody fragments that have previously been confirmed to stimulate the effects of human VISTA. These agonistic anti-human VISTA antibodies and antibody fragments will be beneficial for treating conditions where it is necessary to suppress immunity, especially T cell immunity and / or conditions where VISTA performance is abnormally downregulated. One object of the present invention is to provide novel antibodies and antibody fragments that specifically bind to human VISTA and variants thereof, such as chimeric, human, humanized, or multispecific anti-human VISTA antibodies that specifically bind to human VISTA and promote or mimic the effects of human VISTA on immunity. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment binds to an antigenic determinant that is identical to or overlaps with any of the anti-human VISTA antibodies having CDRs and variable heavy and light chain polypeptides shown in FIG4 . A particular object of the present invention is to provide isolated antibodies or antibody fragments thereof comprising an antigen-binding region that specifically binds to human V-domain Ig inhibitory factor of T-cell activation (human VISTA), wherein the antibody or antibody fragment stimulates or promotes one or more effects of VISTA on immunity, e.g., comprising a human IgG2 constant region or a human IgG2 Fc region, optionally wherein the human IgG2 constant region or Fc region binds to an Fcγ receptor including human CD32A and / or an IgG2 containing a human IgG2 constant region or Fc region comprising a native human IgG2 that binds to an Fcγ receptor and / or binds to an FcγR including hFcγRI (CD64), FcγRIIA or hFcγRIIB, (CD32 or CD32A), and FcγRIIIA (CD16A) or FcγRIIIB (CD16B). A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment binds to an antigenic determinant of VISTA that includes or overlaps with an antigenic determinant bound by any anti-human VISTA antibody having the sequence of Figure 4 . A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment binds to or interacts with one or more residues of an epitope comprising LLDSGLYCCLVVEIRHHHSEHRVH residues. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment binds to or interacts with one or more residues of an antigenic determinant comprising one or more residues of 79EVQTCSERRPIR90, 48NVTLTCRLLGPV60, 153HHHSEHRVHGAM164, 52LTCRLLGPV60, 56LLGPVDKGHDVTFYK70, 113LAQRHGLESASDHHG127, 93TFQDLHLHHGGHQAA107, 146CLVVEIRHHHSEH158, 53TCRLLGPVDKG63 and / or 123SDHHG127. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment binds to or interacts with one or more residues of an antigenic determinant comprising one or more residues of 79EVQTCSERRPIR90. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment promotes or enhances at least one effect of human VISTA on immunity, such as its inhibitory effect on any one or more of T cell immunity, monocyte activation, and induction of T cell proliferation; induction or inhibition of cytokine expression, increase in monocyte survival, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) in cells expressing VISTA; and induction of antibody-dependent cellular phagocytosis (ADCP) in cells expressing VISTA. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment comprises an antigen-binding region that specifically binds to human VISTA, wherein the antibody or antibody fragment comprises variable heavy and light chain sequences having the same CDR polypeptides as any of the anti-human VISTA antibodies having the CDRs and variable heavy and light chain polypeptides shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or antibody fragment, then the antibody or antibody fragment does not comprise the same CDRs as any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody comprising an antagonist anti-human VISTA antibody or fragment does not comprise the same CDRs as any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment comprises a variable heavy chain and / or variable light chain polypeptide having at least 90% sequence identity to those variable heavy chain and / or variable light chain polypeptides of an anti-human VISTA antibody selected from any one of VSTB49-VSTB116, wherein the variable heavy chain and light chain polypeptide sequences are shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or fragment, then the antibody or antibody fragment does not comprise the same CDRs as any one of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53 or VSTB60. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody comprises an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment comprises a variable heavy chain and / or variable light chain polypeptide having at least 95% sequence identity to those variable heavy chain and / or variable light chain polypeptides of an anti-human VISTA antibody selected from any one of VSTB49-VSTB116, wherein the variable heavy chain and light chain polypeptide sequences are shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or antibody fragment, then the antibody or antibody fragment does not comprise the same CDRs as any one of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53 or VSTB60. A particular object of the present invention is to provide agonist antibodies or antibody fragments thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment comprises a variable heavy chain and / or variable light chain polypeptide having at least 96-99% sequence identity to those variable heavy chain and / or variable light chain polypeptides of an anti-human VISTA antibody selected from any one of VSTB49-VSTB116, wherein the variable heavy chain and light chain polypeptide sequences are shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or antibody fragment, then the antibody or antibody fragment does not comprise the same CDRs as any one of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53 or VSTB60. A particular object of the present invention is to provide agonist antibodies or antibody fragments thereof comprising an antigen binding region that specifically binds to human VISTA, wherein the agonist antibody or antibody fragment comprises a variable heavy chain and / or variable light chain polypeptide identical to those of an anti-human VISTA antibody selected from one of VSTB49-VSTB116, wherein the variable heavy chain and light chain polypeptide sequences are shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or antibody fragment, then the antibody or antibody fragment does not comprise the same CDRs as any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53 or VSTB60. A particular object of the present invention is to provide an antagonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, which antagonizes or blocks at least one effect of human VISTA on immunity. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, which stimulates or promotes at least one effect of human VISTA on immunity. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen binding region that specifically binds to human VISTA, comprising a human constant domain. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, comprising a human constant domain selected from IgG1, IgG2, IgG3 and IgG4, which is optionally modified, for example, by deletion, substitution or addition of mutations, or any combination thereof. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, wherein the antibody fragment comprises or is a Fab, F(ab')2 or scFv antibody fragment. A particular object of the present invention is to provide an antagonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA according to any of the foregoing, which blocks or inhibits at least one effect of human VISTA on immunity, for example, selected from its inhibitory effects on T cell immunity, activated monocytes, or T cell proliferation; induction or inhibition of cytokine expression, increase in monocyte survival, inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) of cells expressing VISTA; and inhibition of antibody-dependent cellular phagocytosis (ADCP) of cells expressing VISTA. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA according to any of the foregoing, which promotes or enhances at least one effect of human VISTA on immunity, for example, selected from its inhibitory effects on T cell immunity, activation of monocytes, inhibition of T cell proliferation; induction or inhibition of cytokine expression, increase in monocyte survival rate, inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) in cells expressing VISTA; and inhibition of antibody-dependent cellular phagocytosis (ADCP) of cells expressing VISTA. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, which comprises a human IgG2 constant region or Fc region. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA according to any of the foregoing, which promotes or enhances the inhibitory effect of human VISTA on immunity, such as its effect on any one or more of T cell immunity, monocyte activation, T cell proliferation; cytokine expression, monocyte survival, antibody-dependent cell-mediated cytotoxicity (ADCC) in cells expressing VISTA; and antibody-dependent cellular phagocytosis (ADCP) in cells expressing VISTA. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, which inhibits T cell immunity and / or pro-inflammatory cytokine expression. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, which is a human, humanized or chimeric antibody comprising a human Fc region (e.g., human IgG1, IgG2, IgG3 and IgG4, or a chimera of any of the foregoing). A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen binding region that specifically binds to human VISTA, which is chimeric, human or humanized. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, comprising a potentially mutated human IgG2 constant domain or Fc region. A particular object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA according to any of the foregoing, comprising a human IgG2 constant domain or a fragment thereof, or hIgG1, hIgG3, hIgG4, IgA, IgD, IgE or IgM, wherein the entire or substantially the entire hinge and CH1 domain, and optionally the entire or substantially the entire light chain constant region, of the antibody has been replaced by the corresponding entire or substantially the entire light chain and the hinge and CH1 domain of hIgG2 ("H2 region" or "H2 domain"). A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA according to any of the foregoing, wherein (i) comprises IgG2 The Fc region comprises an Fc region in which the heavy chain cysteine ​​residue at position 127 and the light chain cysteine ​​residue at position 214 (wherein numbering is according to Kabat) are each or both deleted or changed to different amino acid residues, resulting in increased agonist properties of the modified antibody relative to an antibody in which these residues are not changed; (ii) the cysteine ​​residue at position 214 in the H2 region of the antibody is mutated or substituted with another amino acid and / or one or more of the cysteine ​​residues at positions 127, 232 or 233 of the heavy chain are deleted or substituted with another amino acid; (iii) it comprises a human IgG2 constant domain in which at least one cysteine ​​residue is deleted or changed to another amino acid; (iv) it competes with or binds to the same epitope on human VISTA as VSTB95 (variable heavy and light chain sequences shown in FIG4 ). A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human VISTA according to any of the foregoing, which: (i) comprises V sequences of SEQ ID NOs: 100, 101 and 102; HCDRs and V sequences of SEQ ID NOs: 103, 104, and 105 L (ii) V comprising SEQ ID NO: 110, 111 and 112 H CDRs and V sequences of SEQ ID NOs: 113, 114, and 115 L (iii) V comprising SEQ ID NO: 120, 121 and 122 H CDRs and V sequences of SEQ ID NOs: 123, 124, and 125 L (iv) V comprising SEQ ID NO: 130, 131 and 132 H CDRs and V sequences of SEQ ID NOs: 133, 134, and 135 L (v) comprising V of SEQ ID NO: 140, 141 and 142 H CDRs and V sequences of SEQ ID NOs: 143, 144, and 145 L (vi) V comprising SEQ ID NOs: 150, 151 and 152 H CDRs and V sequences of SEQ ID NOs: 153, 154, and 155 L (vii) V comprising SEQ ID NOs: 160, 161 and 162 H CDRs and V sequences of SEQ ID NOs: 163, 164, and 165 L (viii) V comprising SEQ ID NO: 170, 171 and 172 H CDRs and V sequences of SEQ ID NOs: 173, 174, and 175 L CDR (ix) comprising V of SEQ ID NO: 180, 181 and 182 H CDRs and V sequences of SEQ ID NOs: 183, 184, and 185 LCDR (x) comprising V of SEQ ID NO: 190, 191 and 192 H CDRs and V sequences of SEQ ID NOs: 193, 194, and 195 L CDR (xi) comprising V of SEQ ID NO: 200, 201 and 202 H CDRs and V sequences of SEQ ID NOs: 203, 204, and 205 L (xii) V comprising SEQ ID NO: 210, 211 and 212 H CDRs and V sequences of SEQ ID NOs: 213, 214, and 215 L (xiii) V comprising SEQ ID NO: 220, 221 and 222 H CDRs and V sequences of SEQ ID NOs: 223, 224, and 225 L CDR (xiv) comprising V of SEQ ID NO: 230, 231 and 232 H CDRs and V sequences of SEQ ID NOs: 233, 234, and 235 L (xv) comprising V of SEQ ID NO: 240, 241 and 242 H CDRs and V sequences of SEQ ID NOs: 243, 244, and 245 L (xvi) comprising V of SEQ ID NO: 250, 251 and 252 H CDRs and V sequences of SEQ ID NOs: 253, 254, and 255 L (xvii) V comprising SEQ ID NO: 260, 261 and 262 H CDRs and V sequences of SEQ ID NOs: 263, 264, and 265 L (xviii) comprising V of SEQ ID NO: 270, 271 and 272 H CDRs and V sequences of SEQ ID NOs: 273, 274, and 275 L CDR (xix) comprising V of SEQ ID NO: 280, 281 and 282 H CDRs and V sequences of SEQ ID NOs: 283, 284, and 285 L CDR; (xx) comprising V of SEQ ID NO: 290, 291 and 292 H CDRs and V sequences of SEQ ID NOs: 293, 294, and 295 L CDR (xxi) comprising V of SEQ ID NO: 300, 301 and 302 H CDRs and V sequences of SEQ ID NOs: 303, 304, and 305 L (xxii) V comprising SEQ ID NO: 310, 311 and 312 H CDRs and V sequences of SEQ ID NOs: 313, 314, and 315 L (xxiii) V comprising SEQ ID NO: 320, 321 and 322 H CDRs and V sequences of SEQ ID NOs: 323, 324, and 325 L (xxiv) comprising V of SEQ ID NO: 330, 331 and 332 H CDRs and V sequences of SEQ ID NOs: 333, 334, and 335 L CDR (xxv) comprising V of SEQ ID NO: 340, 341 and 342 H CDRs and V sequences of SEQ ID NOs: 343, 344, and 345 L CDR (xxvi) comprising V of SEQ ID NO: 350, 351 and 352 H CDRs and V sequences of SEQ ID NOs: 353, 354, and 355 L CDR (xxvii) comprising V of SEQ ID NO: 360, 361 and 362 H CDRs and V sequences of SEQ ID NOs: 363, 364, and 365 L CDR (xxviii) comprising V of SEQ ID NO: 370, 371 and 372 H CDRs and V sequences of SEQ ID NOs: 373, 374, and 375 L CDR (xxix) comprising V of SEQ ID NO: 380, 381 and 382 H CDRs and V sequences of SEQ ID NOs: 383, 384, and 385 L CDR (xxx) comprising V of SEQ ID NO: 390, 391 and 392 H CDRs and V sequences of SEQ ID NOs: 393, 394, and 395 L CDR (xxxi) comprising V of SEQ ID NO: 400, 401 and 402 H CDRs and V sequences of SEQ ID NOs: 403, 404, and 405 L CDR (xxxii) comprising V of SEQ ID NO: 410, 411 and 412 H CDRs and V sequences of SEQ ID NOs: 413, 414, and 415 L CDR (xxxiii) comprising V of SEQ ID NO: 420, 421 and 422 H CDRs and V sequences of SEQ ID NOs: 423, 424, and 425 L CDR (xxxiv) comprising V of SEQ ID NO: 430, 431 and 432 H CDRs and V sequences of SEQ ID NOs: 433, 434, and 435 LCDR (xxxv) comprising V of SEQ ID NO: 440, 441 and 442 H CDRs and V sequences of SEQ ID NOs: 443, 444, and 445 L CDR (xxxvi) comprising V of SEQ ID NO: 450, 451 and 452 H CDRs and V sequences of SEQ ID NOs: 453, 454, and 455 L CDR (xxxvii) comprising V of SEQ ID NO: 460, 461 and 462 H CDRs and V sequences of SEQ ID NOs: 463, 464, and 465 L CDR (xxxviii) comprising V of SEQ ID NO: 470, 471 and 472 H CDRs and V sequences of SEQ ID NOs: 473, 474, and 475 L CDR (xxxix) comprising V of SEQ ID NO: 480, 481 and 482 H CDRs and V sequences of SEQ ID NOs: 483, 484, and 485 L CDR (xl) comprising SEQ ID NO: 490, 491 and 492 V H CDRs and VL CDR polypeptides of SEQ ID NOs: 493, 494, and 495; (xli) VL CDR polypeptides comprising SEQ ID NOs: 500, 501, and 502 H CDRs and VL CDR polypeptides of SEQ ID NOs: 503, 504 and 505; (xlii) VL CDR polypeptides comprising SEQ ID NOs: 510, 511 and 512 H (xliii) a VL CDR polypeptide comprising SEQ ID NOs: 520, 521, and 522; HCDRs and VL CDR polypeptides of SEQ ID NOs: 523, 524, and 525; (xliv) VL CDR polypeptides comprising SEQ ID NOs: 530, 531, and 532 H (xlv) a VL CDR polypeptide comprising SEQ ID NOs: 540, 541, and 542; H (xlvi) a VL CDR polypeptide comprising SEQ ID NOs: 550, 551, and 552; H (xlvii) a VL CDR polypeptide comprising SEQ ID NOs: 560, 561 and 562; H CDRs and V sequences of SEQ ID NOs: 563, 564, and 565 L CDR (xlviii) comprising V of SEQ ID NO: 570, 571 and 572 H CDRs and V sequences of SEQ ID NOs: 573, 574, and 575 L CDR; (xlix) comprising V of SEQ ID NO: 580, 581 and 582 H CDRs and V sequences of SEQ ID NOs: 583, 584, and 585 L CDR; (1) comprising V of SEQ ID NO: 590, 591 and 592 H CDRs and V sequences of SEQ ID NOs: 593, 594, and 595 L CDR (li) comprising SEQ ID NO: 600, 601 and 602 V H CDRs and V of SEQ ID NOs: 603, 604 and 605 L CDR; (lii) comprising V of SEQ ID NO: 610, 611 and 612 HCDRs and V sequences of SEQ ID NOs: 613, 614, and 615 L CDR; (liii) comprising V of SEQ ID NO: 620, 621 and 622 H CDRs and V sequences of SEQ ID NOs: 623, 624, and 625 L CDR; (liv) comprising SEQ ID NO: 630, 631 and 632 V H CDRs and V sequences of SEQ ID NOs: 633, 634, and 635 L CDR (lv) comprising SEQ ID NO: 640, 641 and 642 V H CDRs and V sequences of SEQ ID NOs: 643, 644, and 645 L CDR (lvi) comprising SEQ ID NO: 650, 651 and 652 V H CDRs and V sequences of SEQ ID NOs: 653, 654, and 655 L CDR (lvii) comprising SEQ ID NO: 660, 661 and 662 V H CDRs and V of SEQ ID NOs: 663, 664 and 665 L CDR (lviii) comprising V of SEQ ID NO: 670, 671 and 672 H CDRs and V sequences of SEQ ID NOs: 673, 674, and 675 L CDR; (11) comprising V of SEQ ID NO: 680, 681 and 682 H CDRs and V sequences of SEQ ID NOs: 683, 684, and 685 L CDR (lx) comprising SEQ ID NO: 690, 691 and 692 V H CDRs and V sequences of SEQ ID NOs: 693, 694, and 695 L CDR (lxi) comprising SEQ ID NO: 700, 701 and 702 V H CDRs and V sequences of SEQ ID NOs: 703, 704, and 705 L CDR (lxii) comprising SEQ ID NO: 710, 711 and 712 V H CDRs and V sequences of SEQ ID NOs: 713, 714, and 715 L CDR (lxiii) comprising SEQ ID NO: 720, 721 and 722 V H CDRs and V sequences of SEQ ID NOs: 723, 724, and 725 L CDR (lxiv) comprising V of SEQ ID NO: 730, 731 and 732 H CDRs and V sequences of SEQ ID NOs: 733, 734, and 735 L CDR (lxv) comprising SEQ ID NO: 740, 741 and 742 V H CDRs and V sequences of SEQ ID NOs: 743, 744, and 745 L CDR (lxvi) comprising V of SEQ ID NO: 750, 751 and 752 H CDRs and V sequences of SEQ ID NOs: 753, 754, and 755 L CDR (lxvii) comprising V of SEQ ID NO: 760, 761 and 762 H CDRs and V sequences of SEQ ID NOs: 763, 764, and 765 L CDR (lxviii) comprising SEQ ID NO: 770, 771 and 772 V H CDRs and V sequences of SEQ ID NOs: 773, 774, and 775 LCDR (lxix) comprising SEQ ID NO: 780, 781 and 782 V H CDRs and V sequences of SEQ ID NOs: 783, 784, and 785 L CDR (lxx) comprising SEQ ID NO: 790, 791 and 792 V H CDRs and V sequences of SEQ ID NOs: 793, 794, and 795 L CDR (lxxi) comprising SEQ ID NO: 800, 801 and 802 V H CDRs and V of SEQ ID NOs: 803, 804 and 805 L CDR (lxxii) comprising SEQ ID NO: 810, 811 and 812 V H CDRs and V of SEQ ID NOs: 813, 814, and 815 L CDR. One object of the present invention is to provide a VISTA agonist according to any of the foregoing, which: (i) comprises V of SEQ ID NO: 106 H Polypeptide and V of SEQ ID NO: 108 L (ii) a polypeptide comprising V of SEQ ID NO: 116 H Polypeptide and V of SEQ ID NO: 118 L (iii) a polypeptide comprising V of SEQ ID NO: 126 H Polypeptide and V of SEQ ID NO: 128 L (iv) polypeptide comprising V of SEQ ID NO: 136 H Polypeptide and V of SEQ ID NO: 138 L (v) polypeptide comprising V of SEQ ID NO: 146 H Polypeptide and V of SEQ ID NO: 148 L (vi) polypeptide comprising V of SEQ ID NO: 156 H Polypeptide and V of SEQ ID NO: 158 L (vii) polypeptide comprising V of SEQ ID NO: 166 H Polypeptide and V of SEQ ID NO: 168 L (viii) polypeptide comprising V of SEQ ID NO: 176 H Polypeptide and V of SEQ ID NO: 178 L (ix) comprising V of SEQ ID NO: 186 H Polypeptide and V of SEQ ID NO: 188 L Polypeptide; (x) comprising V of SEQ ID NO: 196 H Polypeptide and V of SEQ ID NO: 198 L Polypeptide; (xi) comprising V of SEQ ID NO: 206 H Polypeptide and V of SEQ ID NO: 208 L (xii) polypeptide comprising V of SEQ ID NO: 216 H Polypeptide and V of SEQ ID NO: 218 L (xiii) polypeptide comprising V of SEQ ID NO: 226 H Polypeptide and V of SEQ ID NO: 228 L Polypeptide; (xiv) comprising V of SEQ ID NO: 236 H Polypeptide and V of SEQ ID NO: 238 L Polypeptide; (xv) comprising V of SEQ ID NO: 246 HPolypeptide and V of SEQ ID NO: 248 L Polypeptide; (xvi) comprising V of SEQ ID NO: 256 H Polypeptide and V of SEQ ID NO: 258 L (xvii) polypeptide comprising V of SEQ ID NO: 266 H Polypeptide and V of SEQ ID NO: 268 L (xviii) polypeptide comprising V of SEQ ID NO: 276 H Polypeptide and V of SEQ ID NO: 278 L Polypeptide; (xix) comprising V of SEQ ID NO: 286 H Polypeptide and V of SEQ ID NO: 288 L Polypeptide; (xx) comprising V of SEQ ID NO: 296 H Polypeptide and V of SEQ ID NO: 298 L Polypeptide; (xxi) comprising V of SEQ ID NO: 306 H Polypeptide and V of SEQ ID NO: 308 L (xxii) polypeptide comprising V of SEQ ID NO: 316 H Polypeptide and V of SEQ ID NO: 318 L (xxiii) polypeptide comprising V of SEQ ID NO: 326 H Polypeptide and V of SEQ ID NO: 328 L Polypeptide; (xxiv) comprising V of SEQ ID NO: 336 H Polypeptide and V of SEQ ID NO: 338 L Polypeptide; (xxv) comprising V of SEQ ID NO: 346 H Polypeptide and V of SEQ ID NO: 348 L Polypeptide; (xxvi) comprising V of SEQ ID NO: 356 H Polypeptide and V of SEQ ID NO: 358 L Polypeptide; (xxvii) comprising V of SEQ ID NO: 366 H Polypeptide and V of SEQ ID NO: 368 L Polypeptide (xxviii) comprising V of SEQ ID NO: 376 H Polypeptide and V of SEQ ID NO: 378 L Polypeptide; (xxix) comprising V of SEQ ID NO: 386 H Polypeptide and V of SEQ ID NO: 388 L Polypeptide; (xxx) comprising V of SEQ ID NO: 396 H Polypeptide and V of SEQ ID NO: 398 L Polypeptide; (xxxi) comprising V of SEQ ID NO: 406 H Polypeptide and V of SEQ ID NO: 408 L Polypeptide; (xxxii) comprising V of SEQ ID NO: 416 H Polypeptide and V of SEQ ID NO: 418 L Polypeptide; (xxxiii) comprising V of SEQ ID NO: 426 H Polypeptide and V of SEQ ID NO: 428 L Polypeptide; (xxxiv) comprising V of SEQ ID NO: 436 H Polypeptide and V of SEQ ID NO: 438 LPolypeptide; (xxxv) comprising V of SEQ ID NO:446 H Polypeptide and V of SEQ ID NO: 448 L Polypeptide; (xxxvi) comprising V of SEQ ID NO: 456 H Polypeptide and V of SEQ ID NO: 458 L Polypeptide; (xxxvii) comprising V of SEQ ID NO: 466 H Polypeptide and V of SEQ ID NO: 468 L Polypeptide; (xxxviii) comprising V of SEQ ID NO: 476 H Polypeptide and V of SEQ ID NO: 478 L Polypeptide; (xxxix) comprising V of SEQ ID NO: 486 H Polypeptide and V of SEQ ID NO: 488 L Polypeptide; (xl) comprising V of SEQ ID NO: 496 H Polypeptide and V of SEQ ID NO: 498 L Polypeptide; (xli) comprising V of SEQ ID NO: 506 H Polypeptide and V of SEQ ID NO: 508 L Polypeptide; (xlii) comprising V of SEQ ID NO: 516 H Polypeptide and V of SEQ ID NO: 518 L Polypeptide; (xliii) comprising V of SEQ ID NO: 526 H Polypeptide and V of SEQ ID NO: 528 L Polypeptide; (xliv) comprising V of SEQ ID NO: 536 HPolypeptide and V of SEQ ID NO: 533, 534 and 535 L Polypeptide; (xlv) comprising V of SEQ ID NO:546 H Polypeptide and V of SEQ ID NO: 548 L Polypeptide; (xlvi) comprising V of SEQ ID NO:556 H Polypeptide and V of SEQ ID NO: 558 L Polypeptide; (xlvii) comprising V of SEQ ID NO: 566 H Polypeptide and V of SEQ ID NO: 568 L Polypeptide; (xlviii) comprising V of SEQ ID NO: 576 H Polypeptide and V of SEQ ID NO: 578 L Polypeptide; (xlix) comprising V of SEQ ID NO: 586 H Polypeptide and V of SEQ ID NO: 588 L Polypeptide; (1) comprising V of SEQ ID NO: 596 H Polypeptide and V of SEQ ID NO: 598 L Polypeptide; (li) comprising V of SEQ ID NO: 606 H Polypeptide and V of SEQ ID NO: 608 L Polypeptide; (lii) comprising V of SEQ ID NO: 616 H Polypeptide and V of SEQ ID NO: 618 L Polypeptide; (liii) comprising V of SEQ ID NO: 626 H Polypeptide and V of SEQ ID NO: 628 L Polypeptide; (liv) comprising V of SEQ ID NO: 636 H Polypeptide and V of SEQ ID NO: 638 L Polypeptide; (lv) comprising V of SEQ ID NO: 646 H Polypeptide and V of SEQ ID NO: 648 L Polypeptide; (lvi) comprising V of SEQ ID NO: 656 H Polypeptide and V of SEQ ID NO: 658 L Polypeptide; (lvii) comprising V of SEQ ID NO: 666 H Polypeptide and V of SEQ ID NO: 668 L Polypeptide; (lviii) comprising V of SEQ ID NO: 676 H Polypeptide and V of SEQ ID NO: 678 L Polypeptide; (11x) comprising V of SEQ ID NO: 686 H Polypeptide and V of SEQ ID NO: 688 L Polypeptide; (1x) comprising V of SEQ ID NO: 696 H Polypeptide and V of SEQ ID NO: 698 L Polypeptide; (lxi) comprising V of SEQ ID NO:706 H Polypeptide and V of SEQ ID NO: 708 L Polypeptide; (lxii) comprising V of SEQ ID NO: 716 H Polypeptide and V of SEQ ID NO: 718 L Polypeptide; (lxiii) comprising V of SEQ ID NO: 726 H Polypeptide and V of SEQ ID NO: 728 LPolypeptide; (lxiv) comprising V of SEQ ID NO:736 H Polypeptide and V of SEQ ID NO: 738 L Polypeptide; (lxv) comprising V of SEQ ID NO: 746 H Polypeptide and V of SEQ ID NO: 748 L Polypeptide; (lxvi) comprising V of SEQ ID NO: 756 H Polypeptide and V of SEQ ID NO: 758 L Polypeptide; (lxvii) comprising V of SEQ ID NO: 766 H Polypeptide and V of SEQ ID NO: 768 L Polypeptide; (lxviii) comprising V of SEQ ID NO: 776 H Polypeptide and V of SEQ ID NO: 778 L Polypeptide; (lxix) comprising V of SEQ ID NO:786 H Polypeptide and V of SEQ ID NO: 788 L Polypeptide; (lxx) comprising V of SEQ ID NO: 796 H Polypeptide and V of SEQ ID NO: 798 L Polypeptide; (lxxi) comprising V of SEQ ID NO:806 H Polypeptide and V of SEQ ID NO: 808 L polypeptide; and (lxxii) V comprising SEQ ID NO: 816 H Polypeptide and V of SEQ ID NO: 818 L polypeptide. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof according to any of the foregoing, comprising an antigen-binding region that specifically binds to human VISTA, comprising a human IgG2 constant domain, wherein optionally at least one cysteine ​​residue is deleted or changed to another amino acid. A specific object of the present invention is to provide an agonist antibody or antibody fragment thereof comprising an antigen-binding region that specifically binds to human VISTA according to any of the foregoing, which mediates any one or a combination of at least one of the following immunosuppressive effects: (i) reducing immune response, (ii) reducing T cell activation, (iii) reducing cytotoxic T cell activity, (iv) reducing natural killer (NK) cell activity, (v) reducing T cell activity, (vi) reducing pro-inflammatory cytokine secretion, (vii) reducing IL-2 secretion; (viii) reducing IL-1 secretion; Reduce interferon-γ production, (ix) reduce Th1 response, (x) reduce Th2 response, (xi) increase the number and / or activity of regulatory T cells, (xii) increase the activity of regulatory cells and / or one or more of myeloid-derived suppressor cells (MDSC), iMC, interstitial stromal cells, and monocytes expressing TIE2, (xiii) increase the activity of regulatory cells and / or one or more of myeloid-derived suppressor cells (MDSC), iMC, interstitial stromal cells, and monocytes expressing TIE2, (xiii) Increase M2 macrophages, (xiv) increase M2 macrophage activity, (xv) increase N2 neutrophils, (xvi) increase N2 neutrophil activity, (xvii) increase inhibition of T cell activation, (xviii) increase inhibition of CTL activation, (xix) increase inhibition of NK cell activation, (xx) increase T cell depletion, (xxi) reduce T cell responses, (xxii) reduce cytotoxic cell activity, (xxiii) reduce antigen-specific memory responses, (xxiv ) inhibit apoptosis or cytolysis, (xxv) reduce cytotoxic or cytostatic effects on cells, (xxvi) reduce direct cell killing, (xxvii) reduce Th17 activity, and / or (xxviii) reduce complement-dependent cytotoxicity and / or antibody-dependent cell-mediated cytotoxicity, with the proviso that the anti-VISTA antibody or antigen-binding fragment can induce an effect opposite to one or more of (i)-(xxviii) and is optionally used to treat autoimmunity, allergy, inflammation, transplantation or sepsis. A particular object of the present invention is to provide a pharmaceutical or diagnostic composition comprising an agonist antibody or antibody fragment thereof according to any of the aforementioned methods comprising an antigen-binding region that specifically binds to human VISTA. A particular object of the present invention is to provide a therapeutic and / or diagnostic method, or use of a composition comprising at least one antagonist antibody or antibody fragment according to any of the preceding claims for diagnostic or therapeutic purposes, the method or use comprising administering to a subject in need thereof at least one dose or composition comprising a therapeutically or diagnostically effective amount of at least one antagonist antibody or antibody fragment according to any of the preceding claims, such as cancer or an infectious disorder, optionally wherein the cancer is a blood cancer or a solid tumor, such as a tumor surrounded by a tumor stroma comprising myeloid cells, T cells, or a combination of myeloid cells and T cells, or a cancer selected from leukemia, lymphoma, myelodysplasia syndrome or myeloma, lung cancer, or a combination thereof, or a leukemia comprising acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid (myelogenous) leukemia (AML), chronic myeloid leukemia (CML); hairy cell leukemia, T-cell prolymphocytic leukemia, large granular lymphocytic leukemia, or adult T-cell leukemia. A particular object of the present invention is to provide a therapeutic and / or diagnostic method or use of a composition containing at least one agonist antibody or antibody fragment according to any of the preceding claims for diagnostic or therapeutic purposes, the method or use comprising administering to a subject in need thereof at least one dose or composition comprising a therapeutically or diagnostically effective amount of at least one agonist antibody or antibody fragment according to any of the preceding claims or a composition containing the same according to any of the preceding claims. A specific object of the present invention is to provide a method or use of any agonist antibody or antibody fragment according to any of the foregoing for achieving any one or a combination of at least one of the following immunosuppressive effects in vitro and / or in vivo: (i) reducing immune response, (ii) reducing T cell activation, (iii) reducing cytotoxic T cell activity, (iv) reducing natural killer (NK) cell activity, (v) reducing T cell activity, (vi) reducing pro-inflammatory cytokine secretion, (vii) reducing IL-2 secretion; (viii) reducing interference (ix) reducing Th1 response, (x) reducing Th2 response, (xi) increasing the number and / or activity of regulatory T cells, (xii) increasing the activity of regulatory cells and / or one or more of myeloid-derived suppressor cells (MDSC), iMC, interstitial stromal cells, and monocytes expressing TIE2, (xiii) increasing the activity of regulatory cells and / or the activity of one or more of myeloid-derived suppressor cells (MDSC), iMC, interstitial stromal cells, and monocytes expressing TIE2, (xiii) increasing the activity of regulatory cells and / or the activity of one or more of myeloid-derived suppressor cells (MDSC), iMC, interstitial stromal cells, and monocytes expressing TIE2, (xiii) increasing M 2 macrophages, (xiv) increase M2 macrophage activity, (xv) increase N2 neutrophil activity, (xvi) increase N2 neutrophil activity, (xvii) increase inhibition of T cell activation, (xviii) increase inhibition of CTL activation, (xix) increase inhibition of NK cell activation, (xx) increase T cell depletion, (xxi) reduce T cell response, (xxii) reduce cytotoxic cell activity, (xxiii) reduce antigen-specific memory response, (xxiv) Inhibit apoptosis or cytolysis, (xxv) reduce cytotoxic or cytostatic effects on cells, (xxvi) reduce direct cell killing, (xxvii) reduce Th17 activity and / or (xxviii) reduce complement-dependent cytotoxicity and / or antibody-dependent cell-mediated cytotoxicity, with the proviso that the anti-VISTA antibody or antigen-binding fragment can induce an effect opposite to one or more of (i)-(xxviii) and is optionally used to treat autoimmunity, allergy, inflammation, transplantation or sepsis. A particular object of the present invention is to provide methods or uses of any agonist antibody or antibody fragment according to any of the foregoing for treating or preventing allergy, autoimmunity, transplantation, gene therapy, inflammation, cancer, GVHD or sepsis, or for treating or preventing inflammatory, autoimmune or allergic side effects associated with any of the foregoing in a human subject. The anti-VISTA antibody or antigen-binding fragment or composition or method or use according to any of the foregoing further comprises another immunomodulatory antibody or fusion protein selected from an immunosuppressive antibody or fusion protein targeting one or more of CTLA4, PD-1, PDL-1, LAG-3, TIM-3, BTLA, B7-H4, B7-H3, VISTA and / or an agonist antibody or fusion protein targeting one or more of CD40, CD137, OX40, GITR, CD27, CD28 or ICOS. Any of the foregoing methods or uses comprises analyzing VISTA protein in cells or in body fluids of the subject before, concurrently with, and / or after treatment. Any of the foregoing methods or uses comprises analyzing VISTA levels on hematopoietic cells. The methods or uses of any of the foregoing comprise analyzing VISTA levels on hematopoietic cells selected from any one or more of myeloid lineage cells and / or lymphocytes, monocytes or neutrophils, T cells, B cells, natural killer (NK) cells, or natural killer T (NKT) cells. The method or use of any of the foregoing, wherein the agonist anti-human VISTA antibody or fragment comprises the same CDRs as an antibody selected from VSTB49-VSTB116 and an optionally mutated human IgG2 Fc region, or wherein the IgG2 constant region or Fc region retains native FcR binding and / or retains the ability to bind CD32A. The antibody, composition, method or use of any of the foregoing, wherein the anti-human VISTA antibody or fragment has an affinity or KD for human VISTA of 50 M or less as determined by surface plasmon resonance at 37°C. The antibody, composition, method or use of any of the foregoing, wherein the anti-human VISTA antibody or fragment has an affinity or KD for human VISTA of 1 nM or less as determined by surface plasmon resonance at 37°C. A particular object of the present invention is to provide isolated antagonistic and agonistic anti-human VISTA antibodies and agonistic antibody fragments comprising an antigen binding region that specifically binds to human VISTA, wherein the antibody or antibody fragment comprises variable heavy and light chain sequences comprising the CDR polypeptides of any of the anti-human VISTA antibodies having the sequences shown in Figure 4, with the proviso that if the antibody or fragment comprises an antagonist anti-human VISTA antibody or antibody fragment, the antibody or antibody fragment does not comprise CDRs identical to any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. A particular object of the present invention is to provide isolated antagonistic and agonistic anti-human VISTA antibodies and agonistic antibody fragments comprising an antigen-binding region that specifically binds to human VISTA, wherein the antibodies or antibody fragments comprise variable heavy and light chain sequences comprising CDR polypeptides of an anti-human VISTA antibody selected from VSTB49-VSTB116, with the proviso that if the antibody or fragment comprises an antagonistic anti-human VISTA antibody or anti-human VISTA antibody fragment, the anti-human VISTA antibody or antibody fragment does not comprise CDRs identical to any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. Another specific object of the present invention is to provide isolated antagonistic and agonistic antibodies and antibody fragments comprising the CDRs of an anti-human VISTA antibody selected from VSTB49-VSTB116, comprising variable heavy and / or variable light chain polypeptides having at least 90%, 95%, or 96-99% sequence identity to the variable heavy and light chain polypeptide sequences of VSTB49-VSTB116, with the proviso that if the antibody or fragment comprises an antagonistic anti-human VISTA antibody or fragment, the antibody or antibody fragment does not comprise the same CDRs as any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. Another specific object of the present invention is to provide isolated antagonistic and agonistic antibodies or antibody fragments comprising CDRs identical to any one of VSTB49-VSTB116, comprising variable heavy chain and / or variable light chain polypeptides identical in sequence to the variable heavy chain and light chain polypeptides of VSTB49-VSTB116, with the proviso that if the antibody or fragment comprises an antagonistic anti-human VISTA antibody or fragment, the antibody or antibody fragment does not comprise CDRs identical to any one of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. Another specific object of the present invention is to provide isolated antagonistic or agonistic chimeric, human, humanized, multispecific (e.g., bispecific) anti-human VISTA antibodies or antibody fragments comprising an antigen binding region that specifically binds to human VISTA, comprising variable heavy and light chain sequences having CDR polypeptides of any of the anti-human VISTA antibodies comprising the CDRs and variable heavy and light chain polypeptides disclosed in Figure 4, with the proviso that if the antibody or fragment comprises an antagonistic anti-human VISTA antibody or antibody fragment, the antibody or antibody fragment does not comprise CDRs identical to any of VSTB112, VSTB116, VSTB95, VSTB50, VSTB53, or VSTB60. Another specific object of the present invention is to provide novel immunosuppressive agents, i.e., anti-human VISTA antibodies and antibody fragments, such as those containing a human IgG2 constant domain or an IgG2 Fc region, wherein the FcR binding ability of the human IgG2 constant domain or the IgG2 Fc region is maintained or enhanced compared to that of a wild-type human IgG2 constant domain or IgG2 Fc region, which stimulate, elicit or mimic the effects of human VISTA on immunity, such as its inhibitory effects on T cell activity, differentiation and proliferation, and its inhibitory effects on the expression of proinflammatory cytokines. Another specific object of the present invention is to provide novel antagonists, i.e., novel anti-human VISTA antibodies and antibody fragments, which antagonize or block the effects of human VISTA on immunity, particularly its inhibitory effects on T cell activity, differentiation and proliferation, and its inhibitory effects on pro-inflammatory cytokine expression. Another specific object of the present invention is to provide novel immunosuppressive antibodies and antibody fragments that enhance or mimic the inhibitory effect of VISTA on T cell immunity, that is, they inhibit CD4 + or CD8 + T cell proliferation, CD4 + or CD8 + T cell activation and its inhibitory effect on the production of immune cytokines (especially proinflammatory cytokines such as IL-2, IL-4, IL-6, IL-17, TNF-α and / or GM-CSF (granulocyte-macrophage colony-stimulating factor)), and its promotion of the expression of chemokines or chemoattractants (such as KC (keratinocyte chemoattractant) or MIP-2 (macrophage inflammatory protein 2)). Another specific object of the present invention is to provide novel antibodies and antibody fragments that block or reduce the inhibitory effect of VISTA on T cell immunity, that is, they enhance CD4 + or CD8 + T cell proliferation, CD4 + or CD8 +T cell activation and its inhibitory effect on the production of proinflammatory immune cytokines (especially proinflammatory cytokines such as IL-2, IL-4, IL-6, IL-17, TNF-α and / or GM-CSF (granulocyte-macrophage colony-stimulating factor)), and its promotion of the expression of chemokines or chemoattractants (such as KC (keratinocyte chemoattractant) or MIP-2 (macrophage inflammatory protein 2)). Another specific object of the present invention is to provide novel immunosuppressive or agonistic anti-human VISTA antibodies and antibody fragments that have specific antigenic determinant specificity or compete with specific anti-human VISTA antibodies for binding to human VISTA. Another specific object of the present invention is to provide novel immunosuppressive or agonistic anti-human VISTA antibodies and antibody fragments that have specific antigenic determinant specificity or compete with specific anti-human VISTA antibodies for binding to human VISTA, wherein these specific anti-human VISTA antibodies stimulate (enhance, induce or simulate) the inhibitory effect of VISTA on immunity (e.g., its effect on T cell immunity (i.e., CD4 + or CD8 + T cell proliferation, CD4 + or CD8 + T cell activation) and / or the inhibition of the production of pro-inflammatory immune cytokines (such as IL-2, IL-4, IL-6, IL-17, TNF-α and / or GM-CSF (granulocyte-macrophage colony-stimulating factor)) and its promotion of the expression of chemokines or chemoattractants (such as KC (keratinocyte chemoattractant) or MIP-2 (macrophage inflammatory protein 2)). Furthermore, the present invention also relates to specific uses of such agonist anti-human VISTA antibodies and antibody fragments as prophylactic or therapeutic agents, particularly in treating conditions and / or in treating transplant or cell therapy recipients (e.g., CAR-T recipients) or in alleviating inflammatory side effects of certain conditions (such as cancer), where preventing or suppressing or reducing an immune response is therapeutically beneficial, and more particularly where preventing or suppressing or reducing T cell immunity (or more particularly CD4 + or CD8 + T cell-mediated immunity) is beneficial in the treatment of diseases such as autoimmunity, inflammation, allergic disorders, sepsis, and GVHD. Furthermore, the present invention relates to novel antagonistic anti-human VISTA antibodies and antibody fragments for use as prophylactic or therapeutic agents, particularly in the treatment of conditions where it is desirable to boost immunity, such as T cell immunity or CD4 + or CD8 + T cell-mediated immunity is beneficial in the treatment of diseases such as cancer and infectious diseases. Another specific object of the present invention is to provide agonist or antagonist anti-human VISTA antibodies according to the present invention, which have a detectable label, linker or therapeutic moiety attached. Another specific object of the present invention is to provide a diagnostic or therapeutic composition comprising a diagnostically or therapeutically effective amount of an agonist or antagonist anti-human VISTA antibody according to the present invention, for example, a composition containing the same CDRs as any of the antibodies having the sequence shown in Figure 4 suitable for human treatment, such as a composition that can be administered intravenously, subcutaneously or intramuscularly. Another specific object of the present invention is to provide a diagnostic or therapeutic method using an agonist antibody according to the present invention in combination with another immunoagonist, such as a PD-1 or PD-L1 agonist, wherein the PD-1 or PD-L1 agonist is selected from an anti-PD-1 antibody or antibody fragment, an anti-PD-L1 antibody or antibody fragment, a PD-L1 polypeptide or fragment thereof that may be monovalent or multimeric, a PD-1 polypeptide or fragment thereof that may be monovalent or multimeric, or a complex or fusion protein comprising any of the foregoing. Another specific object of the present invention is to provide a diagnostic or therapeutic method using an antagonist antibody according to the present invention in combination with another immune antagonist, such as a PD-1 or PD-L1 antagonist, for example, wherein the PD-1 or PD-L1 agonist is selected from an antagonist anti-PD-1 antibody or antibody fragment, an antagonist anti-PD-L1 antibody or antibody fragment. Another specific object of the present invention is to provide methods for contacting immune cells (e.g., human immune cells) with antagonist or agonist antibodies according to the present invention in vitro or in vivo, for example, wherein the contacted cells are injected into a human subject, such as a subject suffering from cancer or an infectious disease or a subject suffering from an inflammatory, allergic or autoimmune condition. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art. Although methods and materials similar to or equivalent to those described herein may be used in the present invention or in the test of the present invention, suitable methods and materials are described herein. These materials, methods, and examples are illustrative only and are not intended to be limiting. The terms used in conjunction with analytical chemistry, synthetic organic chemistry, and medicine and pharmaceutical chemistry described herein and their laboratory procedures and techniques are well known and commonly used in this technology. Standard techniques can be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, and delivery, as well as treatment of patients. As used in this specification and throughout the claims that follow, the meanings of "a," "an," and "the" include plural references unless the context clearly dictates otherwise. As used herein, "activating receptor" broadly refers to an immune cell receptor that binds an antigen, a complexed antigen (e.g., in the context of an MHC molecule), an Ig-fusion protein, a ligand, or an antibody. Activating receptors include, but are not limited to, T cell receptors (TCRs), B cell receptors (BCRs), cytokine receptors, LPS receptors, complementary receptors, and Fc receptors. For example, T cell receptors are present on T cells and are associated with the CD3 molecule. T cell receptors are stimulated by antigen in the context of MHC molecules (as well as by various T cell activating agents). T cell activation via the TCR results in a variety of changes, such as protein phosphorylation, changes in membrane lipids, ion flux, alterations in cyclic nucleotides, changes in RNA transcription, changes in protein synthesis, and changes in cell volume. For example, T cell receptors are present on T cells and are associated with the CD3 molecule. T cell receptors are stimulated by antigen in the context of MHC molecules (as well as by various T cell activating agents). T cell activation via the TCR results in a variety of changes, such as protein phosphorylation, changes in membrane lipids, ion flux, alterations in cyclic nucleotides, changes in RNA transcription, changes in protein synthesis, and changes in cell volume. As used herein, "adjuvant" refers to an agent used to stimulate the immune system and increase the response to a vaccine without having an effect on any specific antigen itself. "Agonist" herein refers to a molecule, typically an antibody or fusion protein, that enhances or mimics the effects of a specific molecule on immunity. In this application, this generally refers to anti-human VISTA agonist antibodies and antibody fragments that enhance or mimic the effects of human VISTA on immunity, particularly the inhibitory effects of VISTA on T cell immunity (CD4+ and / or CD8+ T cell immunity), the expression of proinflammatory cytokines, and its effects on the expression of specific chemokines and chemoattractants. "Assisting in the diagnosis" or "assisting in the detection" of a disease herein means detecting the expression level of a particular marker polypeptide or expressed RNA, alone or in combination with one or more other markers, to assess whether the subject has cells characteristic of a particular disease state or the onset of a particular disease state, or whether the subject comprises an immune dysfunction, such as immune suppression characterized by VISTA expression or aberrant immune upregulation characterized by cells having reduced levels of VISTA, such as during an autoimmune, inflammatory or allergic response, for example, in individuals with chronic and non-chronic diseases. As used herein, "allergic disease" broadly refers to diseases that involve allergic reactions. More specifically, "allergic disease" is defined as a disease in which an allergen is recognized, in which there is a strong correlation between exposure to the allergen and the onset of pathological changes, and in which the pathological changes have been demonstrated to have an immunological mechanism. In this context, immunological mechanism means that white blood cells exhibit an immune response to the allergen stimulus. As used herein, "amino acid" broadly refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those that have been later modified (e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine). Amino acid analogs are compounds that share the same basic chemical structure (i.e., carbon-bound hydrogen, carboxyl group, amino group) and R groups (e.g., homoserine, norleucine, methionine sulfoxide, methionine methylsulfoxide) as naturally occurring amino acids. Analogs may have modified R groups (e.g., norleucine) or a modified peptide backbone, but retain the same basic chemical structure as naturally occurring amino acids. Amino acid mimetics are compounds that have a structure that differs from the general chemical structure of an amino acid but function in a manner similar to naturally occurring amino acids. As used herein, "anergy" or "tolerance" or "prolonged antigen-specific T cell suppression" or "prolonged immunosuppression" broadly refers to refractoriness to stimuli mediated by activating receptors. Refractoryness is typically antigen-specific and persists after cessation of exposure to the tolerizing antigen. For example, in T cells, anergy (as opposed to unresponsiveness) is characterized by a lack of cytokine production, such as IL-2. T cell anergy occurs when a T cell is exposed to an antigen and receives a first signal (a T cell receptor or CD-3-mediated signal) in the absence of a second signal (a co-stimulatory signal). Under these conditions, re-exposure of the cell to the same antigen (even in the presence of co-stimulatory molecules) results in an inability to produce cytokines and, therefore, an inability to proliferate. However, anergic T cells can increase their response to unrelated antigens and, if cultured with cytokines (e.g., IL-2), can proliferate. For example, T cell anergy can also be observed as a lack of IL-2 production by T lymphocytes as measured by ELISA or by proliferation assays using indicator cell lines. Alternatively, a reporter gene construct can be used. For example, anergic T cells cannot induce IL-2 gene transcription (Kang et al. (1992) Science 257: 1134) under the control of a 5' IL-2 gene enhancer by a heterologous promoter or by a polymer of an API sequence that can be found in the enhancer. Regulating costimulatory signals results in regulation of the effector function of immune cells. "Antagonist" in this article refers to a molecule that blocks or reduces the effect of a specific molecule on immunity, usually an antibody or fusion protein. Generally in this application, this will refer to anti-human VISTA antagonist antibodies and antibody fragments that block or reduce the effect of human VISTA on immunity, especially VISTA on T cell immunity (CD4 + and / or CD8+ T cell immunity), the inhibitory effect of VISTA on the expression of pro-inflammatory cytokines, and the effect of VISTA on the expression of specific chemokines and chemoattractants. As used herein, "antibody" refers broadly to the "antigen binding portion" of an antibody (also used interchangeably with "antibody portion", "antigen binding fragment", "antibody fragment") as well as complete antibody molecules. The term "antigen binding portion" as used herein refers to one or more fragments of an antibody that retains the ability to specifically bind to an antigen (e.g., VISTA or a specific portion thereof). The term "antibody" as mentioned herein includes complete polyclonal and monoclonal antibodies and any antigen binding fragment thereof (i.e., "antigen binding portion") or single chain, as well as bispecific and multispecific antibodies, such as those that bind to multiple antigens or multiple antigenic determinants. "Antibody" refers to a glycoprotein or antigen binding portion thereof comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain comprises at least one heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region comprises three domains, C H1 Each light chain comprises at least one light chain variable region (abbreviated herein as V L ) and the light chain constant region. The light chain constant region comprises a domain CL-V H and V L The regions can be further subdivided into hypervariable regions, called complementarity determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). Each VH and VL comprises three CDRs and four FRs, arranged from amino terminus to carboxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant regions of antibodies mediate the binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. More generally, the term "antibody" is intended to include any molecular structure containing a polypeptide chain whose specific shape conforms to and recognizes an antigenic determinant, wherein one or more non-covalent binding interactions stabilize the complex between the molecular structure and the antigenic determinant. The prototypical antibody molecule is an immunoglobulin, and all types of immunoglobulins (IgG, IgM, IgA, IgE, IgD, etc.) from all sources (e.g., humans, rodents, rabbits, cows, sheep, pigs, dogs, other mammals, chickens, other birds, etc.) are considered "antibodies." The antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Non-limiting examples of antigen-binding fragments encompassed by the term "antigen-binding portion" of an antibody include (a) Fab fragments, which are comprised of V L 、V H、C L and C H1 Monovalent fragment composed of structural domains; (b) F(ab') (c) Fd fragment, which is a bivalent fragment consisting of two Fab fragments linked by a disulfide bond at the hinge region; H and C H1 (d) Fv fragment, which is composed of the VL and VH domains of a single arm of an antibody; (e) dAb fragment (Ward et al. (1989) Nature341: 544-546), which is composed of V H domain composition; and (f) separated complementary determining regions (CDRs). In addition, although the two domains V L and V H Encoded by separate genes, but they can be joined using recombinant methods by synthetic linkers that make them L With V H The two domains pair to form a single protein chain that is a monovalent molecule called a single-chain Fv (scFv). See, for example, Bird et al. (1988). Science 242: 423-426; Huston et al. (1988) Proc Natl. Acad. Sci. USA 85: 5879-5883; and Osbourn et al. (1998) Nat. Biotechnol. 16: 778. Single chain antibodies are also intended to be encompassed within the term "antigen-binding portion" of an antibody. H and V L The sequences can be connected to human immunoglobulin constant region cDNA or genome sequence to produce expression vectors encoding complete IgG molecules or other isotypes. L It can also be used to produce Fab, Fv or other fragments of immunoglobulins using protein chemistry or recombinant DNA technology. Other forms of single-chain antibodies, such as bifunctional antibodies, are also encompassed. Bifunctional antibodies are bivalent bispecific antibodies in which V H and V L The domains are expressed on a single polypeptide chain, but with a linker that is too short to allow pairing between the two domains on the same chain, thereby forcing the domains to pair with the complementary domains of another chain and create two antigen-binding sites. See, e.g., Holliger et al. (1993) Proc Natl. Acad. Sci. USA 90: 6444-6448; Poljak et al. (1994) Structure 2: 1121-1123. Furthermore, an antibody or antigen-binding portion thereof (antigen-binding fragment, antibody fragment, antibody portion) may be part of a larger immunoadhesion molecule formed by covalent or non-covalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of immunoadhesion molecules include tetrameric scFv molecules formed using the streptavidin core region (Kipriyanov et al. (1995) Hum. Antibodies Hybridomas 6: 93-101) and the use of cysteine ​​residues, a labeling peptide and a C-terminal polyhistidine tag to form a bivalent and biotinylated scFv molecule. Kipriyanov et al. (1994) Mol. Immunol. 31: 1047-1058. Antibody portions, such as Fab and F(ab') Fragments of the present invention can be prepared from intact antibodies using conventional techniques, such as by digesting intact antibodies with papain or pepsin, respectively. Furthermore, antibodies, antibody portions, and immunoadhesion molecules can be obtained using standard recombinant DNA techniques as described herein. Antibodies can be polyclonal, monoclonal, xenogeneic, allogeneic, homologous, or modified forms thereof, such as humanized, chimeric, bispecific, or multispecific antibodies. “Antibody that recognizes an antigen” and “antibody specific for an antigen” are used interchangeably herein with the term “antibody that specifically binds to an antigen” and refer to an immunoglobulin or fragment thereof that specifically binds to an antigen. As used herein, "antigen" broadly refers to a molecule or portion of a molecule that can be bound by an antibody that is in turn capable of inducing an animal to produce antibodies that can bind to an antigenic determinant of the antigen. An antigen may have one antigenic determinant or more than one antigenic determinant. The specific reaction referred to herein indicates that the antigen will react in a highly selective manner with its corresponding antibody, rather than with multiple other antibodies that may be elicited by other antigens. In the case of a desired enhanced immune response to a specific antigen of interest, antigens include, but are not limited to, examples of infectious disease antigens to which a protective immune response can be elicited. As used herein, "antigen-presenting cells" broadly refers to professional antigen-presenting cells (e.g., B lymphocytes, monocytes, dendritic cells, and Langerhans cells) as well as other antigen-presenting cells (e.g., keratinocytes, endothelial cells, astrocytes, fibroblasts, and oligodendrocytes). As used herein, "antisense nucleic acid molecule" broadly refers to a nucleotide sequence that is complementary to a "sense" nucleic acid* encoding a protein that is complementary to an mRNA sequence or to the coding strand of a gene (e.g., to the coding strand of a double-stranded cDNA molecule). Thus, an antisense nucleic acid molecule can hydrogen bond to a sense nucleic acid molecule. As used herein, "apoptosis" broadly refers to a progressive cell death that can be characterized using techniques known in the art. Apoptotic cell death can be characterized by cell shrinkage, membrane blebbing, and chromatin condensation that culminate in cell division. Cells undergoing apoptosis also display a characteristic pattern of internucleosomal DNA cleavage. As used herein, "autoimmunity" or "autoimmune disease or condition" refers broadly to diseases or disorders arising from and directed against an individual's own tissues, or their co-isolation or manifestation, or conditions arising therefrom, and includes such conditions. As used herein, autoimmune conditions include inflammatory or allergic conditions, for example, chronic diseases characterized by a host immune response directed against autoantigens potentially associated with tissue destruction, such as rheumatoid arthritis. As used herein, "B cell receptor (BCR)" broadly refers to the complex between membrane immunoglobulin (mIg) and other transmembrane polypeptides (e.g., IgA and Ig) found on B cells. The signal transduction function of mIg is triggered by oligomeric or multimeric antigen crosslinking of the receptor molecule. B cells can also be activated by anti-immunoglobulin antibodies. Following BCR activation, various changes occur in B cells, including tyrosine phosphorylation. As used herein, "cancer" refers broadly to any neoplastic disease (whether invasive or metastatic) characterized by abnormal and uncontrolled cell division, leading to malignant growth or tumors (e.g., dysregulated cell growth). As used herein, the terms "cancer" or "cancerous" should be understood to encompass any neoplastic disease (whether invasive, non-invasive, or metastatic) characterized by abnormal and uncontrolled cell division, leading to malignant growth or tumors, non-limiting examples of which are described herein. This includes any physiological condition in mammals that is typically characterized by dysregulated cell growth. Examples of cancer are exemplified in the working examples. Other cancers include, but are not limited to, carcinomas, lymphomas, blastomas, sarcomas, and leukemias. More specific examples of such cancers include squamous cell carcinoma, lung cancer (including small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma and lung squamous cell carcinoma), peritoneal cancer, hepatocellular carcinoma, gastric cancer or stomach cancer (including gastrointestinal cancer), pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, liver tumors, breast cancer, colon cancer, colorectal cancer, endometrial cancer or uterine cancer, salivary gland cancer, kidney cancer or renal cancer, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, hepatocellular carcinoma and various types of head and neck cancer, as well as B-cell lymphoma (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate / follicular NHL; intermediate-grade diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; bulky lesion NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenström's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); hairy cell leukemia; chronic myeloid leukemia; multiple myeloma and post-transplant lymphoproliferative disorder (PTLD). Other cancers suitable for treatment by the present invention include, but are not limited to, carcinomas, lymphomas, blastomas, sarcomas, and leukemias or lymphoid malignancies.More specific examples of such cancers include colorectal cancer, bladder cancer, ovarian cancer, melanoma, squamous cell carcinoma, lung cancer (including small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma and lung squamous cell carcinoma), peritoneal cancer, hepatocellular carcinoma, stomach cancer (including gastrointestinal cancer), pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, liver tumors, breast cancer, colon cancer, colorectal cancer, endometrial cancer or uterine cancer, salivary gland cancer, kidney cancer, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, liver cancer and various types of head and neck cancer, as well as B-cell lymphomas (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate-grade / follicular NHL; intermediate-grade diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; bulky-lesion NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's macroglobulinemia); chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); hairy cell leukemia; chronic myeloid leukemia; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with nevus hamartomatosis, edema (such as that associated with brain tumors), and Meigs' syndrome. The cancer is preferably selected from the group consisting of the following diseases: colorectal cancer, breast cancer, colorectal cancer, rectal cancer, non-small cell lung cancer, non-Hodgkin's lymphoma (NHL), renal cell carcinoma, prostate cancer, liver cancer, pancreatic cancer, soft tissue sarcoma, Kaposi's sarcoma, carcinoid, head and neck cancer, melanoma, ovarian cancer, mesothelioma and multiple myeloma. In an exemplary embodiment, the cancer is early or late (including metastatic) bladder cancer, ovarian cancer or melanoma. In another embodiment, the cancer is colorectal cancer. Cancerous conditions suitable for treatment of the present invention include cancers that express or do not express VISTA and further include non-metastatic or non-invasive and invasive or metastatic cancers, wherein VISTA is expressed by immune, stromal or diseased cells to suppress anti-tumor responses and anti-invasive immune responses. The method of the present invention is particularly suitable for treating vascularized tumors. Cancers according to the present invention include cancers that do or do not express VISTA and further include non-metastatic or non-invasive as well as invasive or metastatic cancers in which expression of VISTA by immune, stromal or diseased cells suppresses anti-tumor and anti-invasive immune responses, and those cancers characterized by vascularized tumors. As used herein, "chimeric antibody" broadly refers to an antibody molecule in which the constant region, or portion thereof, has been altered, substituted or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and / or species, or to an entirely different molecule that confers new properties to the chimeric antibody, such as an enzyme, toxin, hormone, growth factor, drug, in which the variable region, or portion thereof, has been altered, substituted or exchanged with a variable region of a different or altered antigenic specificity. As used herein, "coding region" broadly refers to regions of the nucleotide sequence that contain codons translated into amino acid residues, while the term "non-coding region" refers to regions of the nucleotide sequence that are not translated into amino acids (eg, 5' and 3' untranslated regions). As used herein, "conservatively modified variants" apply to both amino acid and nucleic acid sequences and, with respect to a particular nucleic acid sequence, broadly refer to conservatively modified variants, referring to those nucleic acids encoding identical or substantially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, substantially identical sequences. Due to the degeneracy of the genetic code, a large number of functionally equivalent nucleic acids encode any given protein. "Silent changes" are a type of conservatively modified nucleic acid change. Each nucleic acid sequence encoding a polypeptide herein also describes every possible silent change of that nucleic acid. Those skilled in the art will recognize that each codon in a nucleic acid (except AUG (which is typically the only codon for methionine) and TGG (which is typically the only codon for tryptophan)) can be modified to produce a functionally equivalent molecule. As used herein, "complementarity determining region," "hypervariable region," or "CDR" refers broadly to one or more of the hypervariable or complementarity determining regions (CDRs) found in the variable region of the light or heavy chain of an antibody. See Kabat et al. (1987) Sequences of Proteins of Immunological Interest National Institutes of Health, Bethesda, Md. Such representations include those described by Kabat et al. (1983) Sequences Hypervariable regions or hypervariable loops in the three-dimensional structure of antibodies as defined by the US Department of Health and Human Services. Chothia and Lesk (1987) J. Mol. Biol. 196: 901-917. The CDRs in each chain are held in close proximity by the framework regions and contribute to the formation of the antigen binding site by the CDRs of the other chain. The amino acids selected in the CDRs have been described as selectivity determining regions (SDRs), which represent the key contact residues used by the CDRs in antibody-antigen interactions (Kashmiri et al. Methods36: 25-34(2005)). As used herein, "control amount" refers broadly to any amount or range of amounts of a marker compared to the test amount of the marker. For example, a control amount of a marker can be the amount of the marker in patients with a particular disease or condition, or in humans without the disease or condition. A control amount can be an absolute amount (e.g., micrograms / ml) or a relative amount (e.g., relative signal intensity). As used herein, "costimulatory receptors" broadly refer to receptors that transmit co-stimulatory signals to immune cells (e.g., CD28 or ICOS). As used herein, the term "inhibitory receptors" includes receptors that transmit negative signals to immune cells (e.g., T cells or NK cells). As used herein, "costimulation" broadly refers to the ability of a co-stimulatory molecule to provide a second non-activating receptor-mediated signal ("co-stimulatory signal") that induces proliferation or effector function. For example, a co-stimulatory signal can lead to cytokine secretion (e.g., in T cells that have received T cell receptor-mediated signals). Immune cells that have received cell receptor-mediated signals (e.g., via activating receptors) may be referred to herein as "activated immune cells." With regard to T cells, the transmission of co-stimulatory signals to T cells comprises a signal transduction pathway that is not inhibited by cyclosporine A. In addition, co-stimulatory signals can induce cytokine secretion (e.g., IL-2 and / or IL-10) in T cells and / or can prevent the induction of anergy to antigens, induce anergy, or induce cell death in T cells. A "costimulatory polypeptide" or "costimulatory molecule" as used herein refers to a polypeptide that modulates T cell responses following interaction with a cell surface molecule on a T cell. As used herein, "costimulatory signal transduction" is the signal transduction activity generated by the interaction of co-stimulatory polypeptides on antigen-presenting cells and their receptors on T cells during antigen-specific T cell responses. Without wishing to be limited by a single hypothesis, it is believed that antigen-specific T cell responses are mediated by two signals: 1) engagement of the T cell receptor (TCR) with the antigenic peptide presented in the context of MHC (signal 1), and 2) a second antigen-independent signal (signal 2) transmitted by contact between different co-stimulatory receptor / ligand pairs. Without wishing to be limited by a single hypothesis, this "second signal" is important for determining the type of T cell response (activation or inhibition) and the intensity and duration of the response, and is regulated by positive and negative signals from co-stimulatory molecules (such as proteins of the B7 family). "B7" polypeptides herein refer to members of the B7 protein family that costimulate T cells, including but not limited to B7-1, B7-2, B7-DC, B7-H5, B7-H1, B7-H2, B7-H3, B7-H4, B7-H6, B7-S3, and biologically active fragments and / or variants thereof. Representative biologically active fragments include the extracellular domain or fragments of the extracellular domain that costimulate T cells. As used herein, "cytoplasmic domain" refers broadly to the portion of a protein that extends into the cytoplasm of a cell. As used herein, "diagnostic" broadly refers to identifying the presence or nature of a pathological condition. Diagnostic methods differ in their sensitivity and specificity. The "sensitivity" of a diagnostic assay is the percentage of diseased individuals that test positive (the percentage of "true positives"). Diseased individuals that are not detected by the assay are "false negatives." Subjects who are not diseased and test negative in the assay are called "true negatives." The "specificity" of a diagnostic assay is 1 minus the false positive rate, where the "false positive rate" is defined as the proportion of non-disease-affected individuals that test positive. Although a particular diagnostic assay may not provide a definitive diagnosis of a condition, it satisfies the requirement if it provides a positive indication that contributes to the diagnosis. As used herein, "diagnosis" or "aiding diagnosis" broadly refers to classifying a disease or symptom, and / or determining the likelihood that an individual has a disease condition (e.g., based on the absence or presence of VISTA expression and / or increased or decreased expression by immune, matrix and / or putative diseased cells); determining the severity of the disease, monitoring the progression of the disease, predicting the outcome of the disease and / or the prospects for recovery. The term "detection" may also encompass any of the above situations, as appropriate. In some embodiments, diagnosing a disease according to the present invention may be affected by determining the level of a polynucleotide or polypeptide of the present invention in a biological sample obtained from a subject, wherein the level determined may be associated with a predisposition to the disease or the presence or absence of the disease. It should be noted that "biological samples obtained from a subject" may also, as appropriate, include samples that have not been physically removed from the subject. As used herein, an "effective amount" broadly refers to an amount of a compound, antibody, antigen, or cell that, when administered to a patient for the treatment of a disease, is sufficient to achieve such treatment of the disease. An effective amount can be an effective prophylactic amount and / or an effective preventive amount. An effective amount can be an amount that effectively reduces signs / symptoms, effectively prevents the occurrence of signs / symptoms, reduces the severity of the occurrence of signs / symptoms, eliminates the occurrence of signs / symptoms, slows the development of the occurrence of signs / symptoms, and / or affects the prevention or treatment of the occurrence of signs / symptoms. An "effective amount" can vary depending on the disease and its severity, as well as the age, weight, medical history, susceptibility, and pre-existing conditions of the patient to be treated. For the purposes of the present invention, the term "effective amount" is synonymous with "therapeutically effective amount." As used herein, "extracellular domain" or "ECD" refers broadly to the portion of a protein that extends from the cell surface. As used herein, "expression vector" broadly refers to any recombinant expression system used for the purpose of constitutively or inducibly expressing the nucleic acid sequences of the present invention in vitro or in vivo in any cell, including prokaryotic, yeast, fungal, plant, insect, or mammalian cells. The term includes linear or circular expression systems. The term includes expression systems that remain episomal or integrated into the host cell genome. Expression systems may or may not be capable of self-replication, i.e., drive only transient expression in the cell. The term includes recombinant expression cassettes that contain only the minimum elements required for transcription of the recombinant nucleic acid. As used herein, "family" refers broadly to polypeptides and nucleic acid molecules of the present invention, and is intended to mean two or more polypeptides or nucleic acid molecules that share a common structural domain or motif and sufficient amino acid or nucleotide sequence homology as defined herein. Family members can be naturally occurring or non-naturally occurring and can be from the same or different species. For example, a family can contain a first polypeptide of human origin and other different polypeptides of human origin, or can contain homologs of non-human origin (e.g., monkey polypeptides). Family members can also share common functional characteristics. As used herein, "Fc receptor" (FcR) broadly refers to the cell surface receptor for the Fc portion of the immunoglobulin (Ig) molecule. Fc receptors are found on a variety of cells involved in immune responses. The human FcRs identified to date are those that recognize IgG (designated FcγR), IgE (FceRI), IgA (FcaR), and polymeric IgM / A (FcεμR). FcRs are found on the following cell types: FceRI (mast cells), FceRII (various leukocytes), FcaR (neutrophils), and FcμR (glandular epithelium, hepatocytes). (Hogg Immunol. Today 9: 185-86 (1988)). The widely studied FcγR is central to cellular immune defense and is responsible for stimulating the release of inflammatory mediators and hydrolytic enzymes involved in the pathogenesis of autoimmune diseases. (Unkeless, Annu. Rev. Immunol. 6: 251-87 (1988)). FcγRs provide an important link between effector cells and Ig-secreting lymphocytes, as macrophage / monocyte, polymorphonuclear leukocyte, and natural killer (NK) cell FcγRs are essential for conferring specific recognition mediated by IgG. Human leukocytes possess at least three different types of FcγRs for IgG: hFcγRI (CD64) (found on monocytes / macrophages), hFcγRIIA or hFcγRIIB (CD32 or CD32A) (found on monocytes, neutrophils, eosinophils, platelets, possibly B cells, and the K562 cell line), and FcγRIIIA (CD16A) or FcγRIIIB (CD16B) (found on NK cells, neutrophils, eosinophils, and macrophages). As used herein, "framework region" or "FR" refers broadly to one or more of the framework regions within the variable regions of the light and heavy chains of an antibody. See Kabat et al., Sequences of Proteins of Immunological Interest National Institutes of Health, Bethesda, Md (1987). These sequences include those amino acid sequence regions intercalated between the CDRs within the variable regions of the light and heavy chains of antibodies. As used herein, "heterologous" refers broadly to a portion of a nucleic acid, indicating that the nucleic acid comprises two or more subsequences not found in the same relationship to each other. For example, nucleic acids are often recombinantly produced, having two or more sequences from unrelated genes arranged to form a new functional nucleic acid (e.g., a promoter from one source and a coding region from another source). Similarly, a heterologous protein indicates that the protein comprises two or more subsequences not found in the same relationship to each other (e.g., a fusion protein). As used herein, "high affinity" broadly refers to a protein that has at least 10 -6 M, better 10 -7 M, or even better at least 10 -8 M and even better at least 10 -9 M, 10 -10 M, 10 -11 M or 10 -12 The "high affinity" of an IgG antibody or fusion protein herein refers to an antibody or fusion protein with a KD of 10 M for the target antigen or receptor. -6 M or 10 -6 Below M, better 10 -7 M or 10 -7 Below M, preferably 10 -8 M or 10 -8 Below M, better 10 -9 M or 10 -9 Below M and even better 10 -10 M, 10 -11 M or 10 -12 M or 10 -12 For antibodies in particular, "high affinity" binding can be different for different antibody isotypes. For example, "high affinity" binding for an IgM isotype refers to an antibody with a KD of 10 -7M or 10 -7 Below M, better 10 -8 M or 10 -8 K below M D of antibodies. As used herein, "homology" broadly refers to the degree of similarity between a nucleic acid sequence and a reference nucleic acid sequence, or between a polypeptide sequence and a reference polypeptide sequence. Homology can be partial or complete. Complete homology indicates that the nucleic acid or amino acid sequences are identical. Partially homologous nucleic acid or amino acid sequences are nucleic acid or amino acid sequences that are not identical to the reference nucleic acid or amino acid sequence. The degree of homology can be determined by, for example, comparing sequences using BlastP software from the National Center for Biotechnology Information (NCBI) using default parameters. The term "sequence identity" can be used interchangeably with "homology." As used herein, "host cell" refers broadly to a cell into which a nucleic acid molecule of the present invention, such as a recombinant expression vector of the present invention, is introduced. Host cells can be prokaryotic cells (e.g., Escherichia coli) or eukaryotic cells, such as yeast, insect (e.g., SF9), amphibian, or mammalian cells, such as CHO, HeLa, HEK-293, for example, cultured cells, transplanted cells, and in vivo cells. The terms "host cell" and "recombinant host cell" are used interchangeably herein. It should be understood that these terms refer not only to the specific target cell, but also to the progeny or potential progeny of that cell. Because certain modifications may occur in the next generation due to mutations or environmental influences, the progeny are not actually identical to the parent cell, but are still included in the scope of the terms as used herein. A "human monoclonal antibody" refers to an antibody displaying a single binding specificity that has a variable region in which the framework and CDR regions are derived from human germline immunoglobulin sequences. In one embodiment, the human monoclonal antibody is produced by a hybridoma comprising B cells obtained from a transgenic non-human animal (e.g., a transgenic mouse) having a genome comprising human heavy and light chain transgenes fused to immortalized cells. This includes fully human monoclonal antibodies and conjugates and variants thereof, for example, when bound to an effector agent such as a therapeutic or diagnostic agent. As used herein, "humanized antibodies" are broadly meant to include antibodies made by non-human cells having variable and constant regions that have been altered to more closely resemble antibodies made by human cells. For example, by altering the amino acid sequence of a non-human antibody to incorporate amino acids found in human germline immunoglobulin sequences. The humanized antibodies of the present invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutagenesis in vivo), for example, in the CDRs. The term "humanized antibody" as used herein also includes antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. As used herein, "hybridization" broadly refers to the physical interaction of complementary (including partially complementary) polynucleotide chains when the chains are aligned antiparallel to each other through the formation of hydrogen bonds between complementary nucleotides. As used herein, "IgV domain" and "IgC domain" broadly refer to domains of Ig superfamily members. These domains correspond to structural units with a unique folding pattern called the Ig fold. The Ig fold comprises a sandwich of two β sheets, each composed of antiparallel β strands of 5 to 10 amino acids, with a conserved disulfide bond between the two sheets in most (but not all) domains. The IgC domains of Ig, TCR, and MHC molecules share the same type of sequence pattern and are referred to as the CI group in the Ig superfamily. Other IgC domains belong to other groups. IgV domains also share a sequence pattern and are referred to as group V domains. IgV domains are longer than C-domains and form another pair of β strands. As used herein, "immune cells" broadly refer to cells of hematopoietic origin that play a role in immune responses. Immune cells include, but are not limited to, lymphocytes, such as B cells and T cells; natural killer cells; dendritic cells; and myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes. As used herein, "immunoassay" broadly refers to an assay that uses an antibody to specifically bind an antigen. An immunoassay can be characterized by using the specific binding properties of a particular antibody to isolate, target, and / or quantify an antigen. As used herein, "immune-related disease (or disorder or condition)" should be understood to encompass any disease disorder or condition selected from the group including, but not limited to, autoimmune diseases, inflammatory disorders, and immune disorders associated with transplant rejection, such as acute and chronic rejection of organ transplants, allogeneic stem cell transplants, autologous stem cell transplants, bone marrow transplants, and graft-versus-host disease. As used herein, "immune response" refers broadly to T cell-mediated and / or B cell-mediated immune responses that are affected by T cell co-stimulation regulation. Exemplary immune responses include B cell responses (e.g., antibody production), T cell responses (e.g., cytokine production and cellular cytotoxicity), and activation of cytokine-responsive cells (e.g., macrophages). As used herein, the term "downregulation" with respect to an immune response includes eliminating any one or more immune responses, while the term "upregulation" with respect to an immune response includes increasing any one or more immune responses. It will be understood that raising one type of immune response may result in a corresponding downregulation of another type of immune response. For example, raising the production of certain cytokines (e.g., IL-10) may result in downregulation of a cellular immune response. An "immune" response, as used herein, refers to the development of humoral (antibody-mediated) and / or cellular (mediated by antigen-specific T cells or their secretory products) responses to a peptide in a recipient patient. The response may be an active response induced by administration of an immunogen or a passive response induced by administration of antibodies or primed T cells. Without wishing to be limited by a single hypothesis, the activation of antigen-specific CD4 T cells by presentation of polypeptide epitopes associated with class II or class I MHC molecules, respectively, is a process that is not limited to the activation of antigen-specific CD4 T cells. + T helper cells and / or CD8 + Cytotoxic T cells trigger a cellular immune response. The response may also include activation of monocytes, macrophages, NK cells, basophils, dendritic cells, astrocytes, microglia, eosinophils, activation or recruitment of neutrophils or other components of innate immunity. + The presence of a cell-mediated immune response can be determined by assays of T cells (T cells) or CTLs (cytotoxic T lymphocytes). The relative contributions of humoral and cellular responses to the protective or therapeutic effects of an immunogen can be determined by isolating antibodies and T cells separately from immunized isogenic animals and measuring the protective or therapeutic effects in a second subject. An "immunogenic agent" or "immunogen" is a moiety that is capable of eliciting an immune response against itself when administered to a mammal, optionally with an adjuvant. "Inflammatory disorders," "inflammatory conditions," and / or "inflammation," as used interchangeably herein, broadly refer to chronic or acute inflammatory diseases and specifically include inflammatory autoimmune diseases and inflammatory allergic conditions. For example, these conditions include inflammatory abnormalities characterized by a dysregulated immune response to noxious stimuli, such as pathogens, damaged cells, or irritants. Inflammatory disorders contribute to a variety of human diseases. Non-immune diseases with etiologic origins in inflammatory processes include cancer, atherosclerosis, and ischemic heart disease. Examples of conditions associated with inflammation include chronic prostatitis, glomerulonephritis, allergies, pelvic inflammatory disease, reperfusion injury, sarcoidosis, vasculitis, interstitial cystitis, normocomplementemic urticarial vasculitis, pericarditis, myositis, antisynthetase syndrome, scleritis, macrophage activation syndrome, Behçet's syndrome, PAPA syndrome, Blau's syndrome, gout, adult and juvenile Still's disease, cryropyrinopathy, Muckle-Wells syndrome, and inflammatory bowel disease. syndrome), familial cold-induced autoinflammatory syndrome, neonatal-onset multisystem inflammatory disease, familial Mediterranean fever, chronic infantile neurological, skin and joint syndrome, systemic juvenile idiopathic arthritis, hyper-IgD syndrome, Schnitzler's syndrome, TNF receptor-associated periodic syndrome (TRAPSP), gingivitis, periodontitis, hepatitis, cirrhosis, pancreatitis, myocarditis, vasculitis, gastritis, gout, gouty arthritis and inflammatory skin diseases selected from the group consisting of psoriasis, atopic dermatitis, eczema, rosacea, urticaria and acne. As used herein, "inhibitory signal" broadly refers to a signal transmitted through inhibitory receptor molecules on immune cells. Signals antagonize signals through activating receptors (e.g., through TCR, CD3, BCR, or Fc molecules) and can, for example, result in inhibition of second messenger production; proliferation; or effector functions in immune cells, such as reduced phagocytosis, antibody production, or cellular cytotoxicity, or result in the inability of immune cells to produce mediators (e.g., cytokines (e.g., IL-2) and / or mediators of allergic responses); or anergy. As used herein, "isolated" refers broadly to material that has been removed from its original environment in which it occurs in nature and has thus been altered by the hand of man from its natural environment and includes "recombinant" polypeptides. An isolated material can be, for example, an exogenous nucleic acid included in a vector system, an exogenous nucleic acid contained within a host cell, or any material that has been removed from its original environment and has thus been altered by the hand of man (e.g., an "isolated antibody"). For example, as used herein, "isolated" or "purified" refers broadly to a protein, DNA, antibody, RNA, or biologically active portion thereof that is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the biological material is derived, or substantially free of chemical precursors or other chemicals when chemically synthesized. As used herein, the term "isolated" refers to a compound of interest (e.g., a polynucleotide or polypeptide) in an environment different from that in which the compound occurs naturally, for example, separated from its natural environment such as by concentrating the peptide to a concentration that it does not occur in nature. "Isolated" includes compounds in samples that are substantially enriched for the compound of interest and / or in which the compound of interest is partially or substantially purified. As used herein, "isolated antibody" is intended to refer to an antibody that is substantially free of other antibodies with different antigenic specificities (e.g., an isolated antibody that specifically binds VISTA), and substantially free of antibodies that specifically bind antigens other than VISTA. In addition, the isolated antibody may be substantially free of other cellular materials and / or chemicals. "Isotype" herein refers to the antibody class (eg, IgM or IgG1) encoded by the heavy chain constant region genes. "K-assoc" or "Ka" as used herein refers broadly to the association rate of a particular antibody-antigen interaction, while the term "Kdiss" or "Kd" as used herein refers to the dissociation rate of a particular antibody-antigen interaction. As used herein, the term "K D " is intended to refer to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). K of an antibody D The values ​​can be determined using methods established in the art, such as BIAcore ® ), ELISA and KINEXA. Used to determine the K D The preferred method is by using surface plasmon resonance, preferably using a biosensor system such as BIAcore ®systems or by ELISA. These methods typically operate at 25°C or 37°C. Antibodies for therapeutic use will typically have a K of 50 nM or less, or more typically 1 nM or less, at 25°C or 37°C when measured by surface plasmon resonance. D . As used herein, "label" or "detectable moiety" refers broadly to a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. As used herein, "low stringency," "medium stringency," "high stringency," or "very high stringency conditions" refer broadly to conditions for nucleic acid hybridization and washing. Guidance for conducting hybridization reactions can be found in Ausubel et al., Short Protocols in Molecular Biology (5th Edition) John Wiley & Sons, NY (2002). Exemplary specific hybridization conditions include, but are not limited to: (1) low stringency hybridization conditions in 6X sodium chloride / sodium citrate (SSC) at about 45°C, followed by at least two washes in 0.2X SSC, 0.1% SDS at 50°C. (For low stringency conditions, the washing temperature can be increased to 55°C); (2) moderate stringency hybridization conditions in 6X SSC at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 60°C; (3) high stringency hybridization conditions in 6X SSC at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 65°C; and (4) very high stringency hybridization conditions are 0.5 M sodium phosphate, 7% SDS at 65°C, followed by one or more washes in 0.2X SSC and 1% SDS at 65°C. As used herein, "mammal" refers broadly to any and all warm-blooded vertebrates of the class Mammalia, including humans, characterized by hair covering the skin and, in females, milk-producing mammary glands for feeding their young. Examples of mammals include, but are not limited to, alpacas, armadillos, capybaras, cats, camels, chimpanzees, chinchillas, cows, dogs, goats, gorillas, hamsters, horses, humans, lemurs, llamas, mice, non-human primates, pigs, rats, sheep, shrews, squirrels, tapirs, and voles. Mammals include, but are not limited to, bovines, canines, equines, felines, murines, ovines, suicides, primates, and rodents. Mammals also include any and all mammals listed in the World's Mammal Species Index maintained by the Smithsonian Institution, National Museum of Natural History, Washington, D.C. "Multispecific antibodies" refer to antibodies that have two or more antigen-binding regions. This includes bispecific antibodies. These antigen-binding regions can bind to different antigens or different antigenic determinants of the same antigen. As used herein, "naturally occurring nucleic acid molecule" refers broadly to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (eg, encodes a natural protein). As used herein, "nucleic acid" or "nucleic acid sequence" refers broadly to deoxyribonucleotides or ribonucleotide oligonucleotides in single-stranded or double-stranded form. The term encompasses nucleic acids containing known analogs of natural nucleotides, i.e., oligonucleotides. The term also encompasses nucleic acid-like structures with synthetic backbones. Unless otherwise indicated, a particular nucleic acid sequence implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences as well as the explicitly indicated sequence. The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide. As used herein, "operably linked" broadly refers to when two DNA fragments are joined such that the amino acid sequences encoded by the two DNA fragments remain in frame. As used herein, "paratope" broadly refers to the portion of an antibody that recognizes an antigen (e.g., the antigen-binding site of an antibody). The paratope can be a small region of the Fv region of an antibody (e.g., 15 to 22 amino acids) and can contain portions of both the heavy and light chains of an antibody. See Goldsby et al., Antigens (Chapter 3) Immunology (5th ed.) New York: WH Freeman and Company, pp. 57-75. "Patient" or "subject" or "recipient," "individual," or "treated individual" are used interchangeably herein and refer broadly to any animal in need of treatment to alleviate a disease state or prevent the occurrence or recurrence of a disease state. Furthermore, "patient," as used herein, refers broadly to any animal that has risk factors, a history of disease, a susceptibility, symptoms and signs, has been previously diagnosed, is at risk for, or is a member of a patient population for a disease. A patient can be a clinical patient, such as a human, or a veterinary patient, such as a companion, domestic, livestock, exotic, or zoo animal. "Polypeptide," "peptide," and "protein" are used interchangeably and broadly to refer to polymers of amino acid residues of any length, regardless of modification (e.g., phosphorylation or glycosylation). The terms apply to amino acid polymers in which one or more amino acid residues is an analog or mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. The terms apply to amino acid polymers in which one or more amino acid residues is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. Polypeptides can be modified, for example, by the addition of carbohydrate residues to form glycoproteins. The terms "polypeptide," "peptide," and "protein" expressly include glycoproteins as well as non-glycoproteins. As used herein, "promoter" broadly refers to an array of nucleic acid sequences that directs the transcription of a nucleic acid. As used herein, a promoter includes essential nucleic acid sequences near the start site of transcription, such as the TATA element in the case of a polymerase II type promoter. A promoter may also optionally include distal enhancer or repressor elements, which may be located up to several thousand base pairs from the start site of transcription. A "constitutive" promoter is one that is active under most environmental and developmental conditions. An "inducible" promoter is one that is active under environmental or developmental regulation. As used herein, a "prophylactically effective amount" broadly refers to an amount of a compound that, when administered to a patient for the purpose of preventing a disease or preventing the recurrence of a disease, is sufficient to achieve such prevention of the disease or recurrence. A prophylactically effective amount may be an amount effective to prevent the occurrence of signs and / or symptoms. A "prophylactically effective amount" may vary depending on the disease and its severity, as well as the age, weight, medical history, susceptibility to the condition, and pre-existing conditions of the patient being treated. "Preventive vaccine" and / or "preventive vaccination" refers to a vaccine used to prevent illness or symptoms associated with a disease, such as cancer or an infectious condition. As used herein, "prevention" broadly refers to a course of treatment in which signs and / or symptoms are absent from a patient, are in remission, or were previously present in a patient. Prevention includes preventing a disease from developing in a patient after treatment for the disease has been administered. Additionally, prevention includes treating a patient who may develop the disease, particularly a patient who is susceptible to the disease (e.g., a patient who has risk factors or is a member of a patient population at risk for developing the disease). As used herein, "recombinant" with respect to a product refers broadly to a product, such as a cell or nucleic acid, protein, or vector, indicating that the cell, nucleic acid, protein, or vector has been modified by the introduction of a heterologous nucleic acid or protein or by the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, a recombinant cell expresses genes that are not found in the native (non-recombinant) form of the cell or expresses native genes that are abnormally expressed, underexpressed, or not expressed at all. As used herein, the term "recombinant human antibody" includes all human antibodies prepared, expressed, generated, or isolated by recombinant means, such as (a) antibodies isolated from animals (e.g., mice) that are transgenic or transchromosomal for human immunoglobulin genes or fusion tumors prepared therefrom (described further below), (b) antibodies isolated from host cells transformed to express human antibodies (e.g., from transfectomas), (c) antibodies isolated from recombinant combinatorial human antibody libraries, and (d) antibodies prepared, expressed, generated, or isolated by any other means involving splicing human immunoglobulin gene sequences to other DNA sequences. Such recombinant human antibodies have variable regions in which the framework and CDR regions are derived from human germline immunoglobulin sequences. However, in certain embodiments, such recombinant human antibodies may be subjected to in vitro mutagenesis (or in vivo somatic mutagenesis when an animal that is transgenic for human Ig sequences is used), and thus the V H and V L The amino acid sequences of the VH and VL regions, while derived from and related to human germline VH and VL sequences, do not naturally occur in the human antibody germline repertoire in vivo. As used herein, a "signal sequence" or "signal peptide" broadly refers to a peptide containing about 15 or more amino acids that appears at the N-terminus of a secreted, membrane-bound polypeptide and contains a large number of hydrophobic amino acid residues. For example, a signal sequence contains at least about 10 to 30 amino acid residues, preferably about 15 to 25 amino acid residues, more preferably about 18 to 20 amino acid residues, and even more preferably about 19 amino acid residues, and has at least about 35-65%, preferably about 38-50%, and more preferably about 40-45% hydrophobic amino acid residues (e.g., valine, leucine, isoleucine, or phenylalanine). A "signal sequence" (also referred to in the art as a "signal peptide") is used to direct a polypeptide containing the sequence to the lipid bilayer and to cleave it secretly. As used herein, "specifically (or selectively) binds" to an antibody or "specifically (or selectively) is immunoreactive with" or "specifically interacts or binds" refers broadly to a protein or peptide (or other antigenic determinant), and in some embodiments refers to a binding reaction that determines the presence of a protein in a heterogeneous population of proteins or other organisms. For example, under specified immunoassay conditions, a specified antibody binds to a specific protein at least two-fold greater than background (nonspecific signal) and does not bind to substantially any other proteins present in the sample. A specific or selective reaction will typically be at least two-fold greater than background signal or noise, and more typically greater than about 10-fold to 100-fold greater than background. As used herein, "specifically hybridizable" and "complementary" broadly refer to the ability of a nucleic acid to form hydrogen bonds with another nucleic acid sequence by traditional Watson-Crick or other non-traditional types. The binding free energy of a nucleic acid molecule and its complementary sequence is sufficient to allow the nucleic acid to perform its associated function, such as RNAi activity. Determination of the binding free energy of nucleic acid molecules is well known in the art. (See, e.g., Turner et al. CSH Symp. Quant. Biol. LII: 123-33 (1987); Frier et al. PNAS83: 9373-77 1986); Turner et al. J. Am. Chem. Soc. 109:3783-85 (1987). Percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule that can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., about at least 5, 6, 7, 8, 9, 10 out of 10, i.e., about at least 50%, 60%, 70%, 80%, 90%, and 100% complementary, inclusive). "Perfect complementarity" or 100% complementarity broadly refers to all contiguous residues in a nucleic acid sequence hydrogen bonded to the same number of contiguous residues in a second nucleic acid sequence. "Substantially complementary" refers to polynucleotide chains that exhibit approximately at least 90% complementarity, excluding regions of the polynucleotide chain that are selected to be non-complementary, such as overhangs. Specific binding requires a sufficient degree of complementarity to prevent non-specific binding of the oligomeric compound to non-target sequences under conditions where specific binding is desired (i.e., under physiological conditions in the case of in vivo assays or therapeutic treatments, or under assay conditions in the case of in vitro assays). Non-target sequences typically differ by at least 5 nucleotides. As used herein, "sign" of disease refers broadly to any abnormality detectable on examination of a patient that is indicative of disease; objective indications of disease as opposed to symptoms, which are subjective indications of disease. As used herein, "solid support," "support," and "substrate" refer broadly to any material that provides a solid or semisolid structure to which another material can be attached, including but not limited to smooth supports such as metal, glass, plastic, silicon, and ceramic surfaces, as well as textured and porous materials. As used herein, "soluble extracellular domain (ECD)" or "extracellular domain" or "soluble VISTA protein / molecule" of VISTA means a non-cell surface-bound VISTA molecule or any portion thereof, including but not limited to: a VISTA fusion protein or a VISTA ECD-Ig fusion protein (in which the extracellular domain of VISTA or a fragment thereof is fused to an immunoglobulin (Ig) portion, rendering the fusion molecule soluble), or fragments and derivatives thereof; a protein in which the extracellular domain of VISTA is fused or conjugated to a portion of a biologically or chemically active protein, such as the papillomavirus E7 gene product, the melanoma-associated antigen p97, or the HIV env protein, or fragments and derivatives thereof; a hybrid (chimeric) fusion protein (such as VISTA-Ig), or fragments and derivatives thereof. Such fusion proteins are described in more detail below. "Soluble VISTA proteins / molecules" herein also include VISTA molecules in which the transmembrane domain has been removed to render the protein soluble, or fragments and derivatives thereof; fragments, portions or derivatives thereof; and soluble VISTA mutant molecules. The soluble VISTA molecules used in the methods according to at least some embodiments of the present invention may or may not include a signal (leader) peptide sequence. In the context of treatment or diagnosis herein, "subject" or "patient" or "individual" includes any human or non-human animal. The term "non-human animal" includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc., that is, any one suitable for treatment according to the present invention, including (but not limited to) avian and mammalian subjects and preferably mammals. Any mammalian subject in need of treatment according to the present invention is suitable. Human subjects of both sexes and at any stage of development (i.e., neonates, infants, adolescents, puberty and adults) can be treated according to the present invention. The present invention can also be carried out in animal subjects, particularly mammalian subjects, such as mice, rats, dogs, cats, cows, goats, sheep and horses, for veterinary purposes and for drug screening and drug development purposes. "Subject" and "individual" and "patient" are used interchangeably. As used herein, "substantially free of chemical precursors or other chemicals" broadly refers to VISTA protein preparations in which the protein is separated from chemical precursors or other chemicals involved in protein synthesis. In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes VISTA protein preparations having less than about 30% (by dry weight) chemical precursors or non-VISTA chemicals, more preferably less than about 20% chemical precursors or non-VISTA chemicals, even more preferably less than about 10% chemical precursors or non-VISTA chemicals, and most preferably less than about 5% chemical precursors or non-VISTA chemicals. As used herein, "symptoms" of a disease refer broadly to any pathological phenomena or deviations from normal structure, function, or sensation experienced by a patient and indicative of the disease. As used herein, "T cells" broadly refer to CD4+ T cells and CD8+ T cells. The term T cell also includes T helper type 1 T cells and T helper type 2 T cells. As used herein, "therapy" refers broadly to treating a disease, arresting or reducing the progression of a disease or its clinical symptoms, and / or alleviating a disease, resulting in regression of the disease or its clinical symptoms. Treatment encompasses preventing, curing, remedying, reducing, alleviating, and / or alleviating a disease, signs, and / or symptoms of a disease. Treatment encompasses alleviating signs and / or symptoms in a patient experiencing ongoing signs and / or symptoms of a disease (e.g., inflammation, pain). Treatment also encompasses "prevention." The term "reduction," as used for therapeutic purposes, broadly refers to a clinically significant reduction in signs and / or symptoms. Treatment includes treating recurring or recurring signs and / or symptoms (e.g., inflammation, pain). Treatment encompasses, but is not limited to, eliminating the appearance of signs and / or symptoms at any time, as well as reducing existing signs and / or symptoms and eliminating existing signs and / or symptoms. Treatment includes treating chronic diseases ("maintenance") as well as acute diseases. For example, treatment includes treating or preventing the recurrence or recurrence of signs and / or symptoms (e.g., inflammation, pain). As used herein, "Treg cells" (sometimes also referred to as suppressor T cells or induced Treg cells or iTregs) refer to a subset of T cells that regulate the immune system and maintain tolerance to self-antigens and can terminate autoimmune diseases. + CD4 + CD25 + Regulatory T cells (Tregs) are important for maintaining peripheral tolerance under normal conditions. As used herein, "transmembrane domain" broadly refers to an amino acid sequence of about 15 amino acid residues in length that spans the plasma membrane. The transmembrane domain preferably comprises at least about 20, 25, 30, 35, 40 or 45 amino acid residues and spans the plasma membrane. The transmembrane domain is enriched in hydrophobic residues and typically has an α-helical structure. In one embodiment, at least 50%, 60%, 70%, 80%, 90%, 95% or more of the amino acids in the transmembrane domain are hydrophobic, such as leucine, isoleucine, tyrosine or tryptophan. The transmembrane domain is described, for example, in Zagotta et al. Described in Annu. Rev. Neurosci. 19:235-263 (1996). As used herein, "transgenic animal" broadly refers to a non-human animal, preferably a mammal, more preferably a mouse, in which one or more cells of the animal include a "transgene." The term "transgene" refers to exogenous DNA that is integrated into the genome of the cells that gave rise to the transgenic animal and is retained in the genome of the mature animal, for example, to direct the expression of the encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, "anergy" broadly refers to the refractoriness of immune cells to stimulation, for example, by activating receptors or cytokines. Anergy can occur, for example, as a result of exposure to immunosuppressants or high doses of antigen. As used herein, "variable region" or "VR" broadly refers to the domains in each pair of light and heavy chains of an antibody that are directly involved in binding the antibody to the antigen. Each heavy chain has a variable domain (V H ), followed by multiple constant domains. Each light chain has a variable domain (V L ) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain and the light chain variable domain is aligned with the variable domain of the heavy chain. As used herein, "vector" refers broadly to a nucleic acid molecule capable of transporting another nucleic acid molecule to which it is connected. One type of vector is a "plastid," which refers to a circular double-stranded DNA loop in which other DNA segments can be joined. Another type of vector is a viral vector, in which other DNA segments can be joined to the viral genome. Certain vectors are capable of autonomous replication in the host cell into which they are introduced (e.g., bacterial vectors and additional mammalian vectors with bacterial replication origin). Other vectors (e.g., non-additional mammalian vectors) are integrated into the genome of the host cell when introduced into the host cell, and are thereby replicated together with the host genome. In addition, certain vectors are capable of guiding the expression of genes to which they are operably connected. Vectors are referred to herein as "recombinant expression vectors" or simply "expression vectors." Generally speaking, expression vectors used in recombinant DNA technology are often in the form of plastids. In this specification, "plastids" and "vectors" are used interchangeably because plasmids are the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication-defective retroviruses, adenoviruses, and adeno-associated viruses), which serve equivalent functions. Such techniques and procedures are generally performed according to conventional methods well known in the art and as described in various general and more specific references cited and discussed throughout this specification. See, for example, Sambrook et al. Molec. Cloning: Lab. Manual [3rd ed.] Cold Spring Harbor Laboratory Press (2001). Standard techniques can be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Enzymatic reactions and purification techniques can be performed according to manufacturer's specifications or as commonly performed in the art or as described herein. While certain terms and phrases used in this application have been defined, the anti-VISTA antibodies and antigen-binding antibody fragments encompassed by the present invention, as well as methods for their production and uses, are further described below. The present invention relates to antibodies and antibody fragments comprising an antigen-binding region that binds to the V-domain Ig inhibitory factor of T cell activation (VISTA). VISTA is a checkpoint regulator that negatively inhibits immune responses. See Wang et al., “VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses,” J. Exp. Med., 208(3) 577-92 (2011). This protein is expressed on normal human neutrophils, monocytes, and T cell subsets. In addition, cynomolgus monkey cells express VISTA in a pattern similar to normal human cells. VISTA is also expressed in peripheral blood cells, such as those of cancer patients. According to the present invention, the binding of an antagonist anti-VISTA antibody or antibody fragment to VISTA will antagonize at least one effect of VISTA on immunity, thereby inhibiting the inhibitory effect of VISTA on immunity, such as T cell immunity and / or cytokine expression. In contrast, according to the present invention, the binding of an agonist anti-VISTA antibody or antibody fragment to VISTA will stimulate, elicit or simulate at least one effect of VISTA on immunity, thereby promoting at least one inhibitory effect of VISTA on immunity, such as inhibiting T cell immunity or inhibiting the expression of specific proinflammatory cytokines or its promoting effect on the expression of certain chemoattractants and chemokines. Such antibody fragments include, for example, Fab, F(ab') 2 and scFv antibody fragments. Such antibodies or antibody fragments may comprise an antibody constant region or a fragment or variant thereof. Such antibodies and antibody fragments include those that bind to VISTA proteins expressed on hematopoietic and other cells (e.g., bone marrow cells and / or lymphocytes, monocytes, neutrophils, T cells, natural killer (NK) cells, natural killer T (NKT) cells, tumor cells) and / or in the tumor microenvironment (TME). The tumor microenvironment is the cellular environment of the tumor. It may include surrounding immune cells, fibroblasts, blood vessels, other cells, signal transduction molecules, and extracellular matrix. Antibodies that block or inhibit the effects of VISTA can be used to enhance human immune responses, particularly against malignancies and infections. In contrast, molecules that stimulate VISTA (such as soluble VISTA) (e.g., VISTA-Ig) and the agonist anti-human VISTA antibodies and fragments of the present invention can be used to suppress unwanted human immune responses (such as autoimmunity, allergy, GVHD, sepsis) or adverse inflammatory immune responses. The present application provides novel antagonist and agonist anti-human VISTA antibodies, including those comprising the same CDRs as any anti-human VISTA antibody having the sequence shown in Figure 4. Although a variety of antagonist anti-human VISTA antibodies have been reported in the literature prior to the present invention, no agonist anti-human VISTA antibodies or antibody fragments have been reported. As disclosed in the Experimental Examples below, the present inventors initially generated two chimeric anti-human VISTA antibodies derived from a murine anti-human VISTA antibody (1E8 having the sequence in FIG4 ), each containing an unmodified IgG2 human constant region or an IgG2 constant region in which the cysteine ​​residue at position 127 of the kappa chain was changed to a serine residue. As shown in the Examples and Figures cited herein, both antibodies were found to stimulate or mimic the suppressive effects of VISTA on immunity, based at least on (i) their ability to reduce the expression of certain proinflammatory cytokines, such as IL-2, IL-4, IL-6, IL-17, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), as well as certain chemokines or chemoattractants, such as KC (keratinocyte-derived chemokine) or MIP-2 (macrophage inflammatory protein-2); (ii) suppress T cell activity in a GVHD model; and (iii) suppress CD3-driven T cell responses. In addition, after separating the two agonist antibodies, 10 additional chimeric agonist anti-human VISTA antibodies containing human IgG2 constant regions or Fc regions were obtained using similar methods. These antibodies are derived from antibodies referred to herein as GG8, VSTB95 (INX903), VSTB103 (INX904), VSTB53 (INX905), VSTB92 (INX908), VSTB50 (INX900), VSTB56 (INX901), VSTB63 (INX902), VSTB54 (INX906), and VSTB66 (INX907) (having the sequences in Figure 4). Specifically, the chimeric anti-human VISTA antibodies have the variable sequences and human IgG2 constant regions shown in Figure 4. As reported in Tables 1 and 2 below, when evaluated using antibody binning, the anti-human VISTA antibodies were found to bind to two different groups of antigenic determinants, designated Group 1 and Group 2. As shown in Figure 4, the antigenic determinants corresponding to Group 2 include residues in two different peptides present in human VISTA (i.e., NLTLLDSGL and VQTGKDAPSNC). As shown in Tables 1 and 2 below, these 12 different anti-human VISTA antibodies were found to be immunosuppressive in at least one immunosuppression model and multiple antibodies were immunosuppressive in several immunosuppression models. Specifically, INX905, INX908, INX901, INX902, and INX906 demonstrated immunosuppression in two different assay formats. Although all of these antibodies were immunosuppressive and appeared to elicit, promote, or stimulate the immunosuppressive effects of VISTA, INX901, INX902, INX906, and INX908 appeared to be the most immunosuppressive. In addition, other chimeric anti-human VISTA antibodies comprising human IgG2 constant domains containing the variable sequences of other anti-VISTA antibodies shown in Figure 4 will be screened according to their immunosuppressive properties and their ability to stimulate or simulate the immunosuppression and other effects of human VISTA. Based on the results obtained so far, this screening should identify other agonist anti-human VISTA antibodies, especially those antibodies that bind to the same antigenic determinants. In addition, agonist anti-human VISTA antibodies according to the present invention have been shown to be effective (immunosuppression) in a variety of autoimmune and inflammatory animal disease models, including arthritis, lupus or SLE, GVHD, inflammatory bowel disease (IBD) or colitis, chronic and acute infectious diseases or hepatotoxicity and psoriasis animal models. Based on the above, the anti-human VISTA agonist antibodies of the present invention should be suitable for therapeutic and prophylactic treatment of autoimmune, allergic and inflammatory conditions. As shown, chimeric IgG2 anti-human VISTA antibodies having the sequence shown in Figure 4 have been shown to be immunosuppressive in different immunosuppression models. In addition, these antibodies elicit these immunosuppressive effects in a specific immunomodulatory manner, rather than by achieving depletion of specific types of T cells or by depleting T cells in general. As further shown in the examples, chimeric IgG2 agonist anti-human VISTA antibodies containing mutations in the hinge region induce substantially the same inhibitory effect on immunity, that is, mutations in the IgG2 constant region do not seem to induce an enhancement of the inhibitory effect under the test experimental conditions. On the contrary, both IgG2A and IgG2 B forms and their mixtures induce the same immunosuppressive effect. In addition, based on the experiments disclosed in the examples, it seems that FcγR binding may contribute to the agonist properties of the anti-human VISTA antibodies of the present invention. In particular, it was found that the inclusion of a silent IgG2 constant region eliminated the immunosuppressive properties of the tested agonist antibodies. Based on these results, it is assumed that one or more FcγRs may affect the agonist properties of these antibodies and in particular it is assumed that FcγRIIA (CD32 or CD32A) or FcγRIIB (CD32B) binding may be involved in the agonist properties of the agonist antibodies of the present invention. Using these same methods, it is expected that other agonist anti-human VISTA IgG2 antibodies can be obtained, such as other antibodies derived from anti-human VISTA antibodies with the sequence shown in Figure 4. As mentioned, 12 agonist anti-human VISTA antibodies have been obtained to date, including those with the sequence contained in Figure 4. Based on these results, it is expected that other agonist anti-human VISTA antibodies can be produced and display immunosuppression. It is also expected that other agonist anti-human VISTA antibodies that bind to the same or overlapping antigenic determinants and / or compete with any antibody containing the sequence shown in Figure 4 can be produced. In an exemplary embodiment, these antibodies will bind to the antigenic determinants corresponding to Group 1 or Group 2 antibodies or will compete with these antibodies for binding to human VISTA. Methods for identifying specific antigenic determinants bound by antibodies are known in the art. In the operating examples, the applicant discloses an explanation of the antigenic determinants bound by a variety of anti-VISTA antibodies according to the present invention. Therefore, in exemplary embodiments, the agonist anti-human VISTA antibody according to the present invention will include an IgG2 constant region or fragment thereof in the A form, the B form, or a mixture thereof. In exemplary embodiments, the antibodies will bind to one or more FcγRs, for example, they will bind to an FcγR identical to a complete or wild-type human IgG2 Fc region. In other exemplary embodiments, the antibody will bind to CD32 (CD32A and / or CD32B). This can be achieved by using a wild-type or modified IgG2 constant region that binds to CD32 (CD32A and / or CD32B). In addition, the agonist antibody can be modified to incorporate another polypeptide, such as another Fc polypeptide or antigen binding region that binds to FcγR (such as CD32A and / or CD32B). The IgG2 Fc or constant region contained in the agonist anti-human VISTA antibody of the present invention may be modified as appropriate, for example, to change effector function, for example, to change FcR binding, FcRN binding, complement binding, glycosylation and the like. Specifically, the IgG2 Fc or constant region contained in the agonist anti-human VISTA antibody of the present invention may be modified by converting the cysteine ​​at position 27 or further optionally by converting another cysteine ​​residue or other residue in the hinge region to another amino acid (e.g., serine). Other possible Fc modifications are disclosed below. These VISTA agonist antibodies can be used to treat or prevent disease conditions or to treat, reduce, or alleviate pathological effects associated with such conditions (e.g., inflammation), in which suppressing T cell immunity or expression of pro-inflammatory cytokines and / or increasing expression of chemokines and chemoattractants is therapeutically or prophylactically beneficial. These conditions specifically include autoimmunity, allergies, inflammatory disorders, sepsis, GVHD, and for suppressing undesirable T cell immune responses against transplanted cells, tissues, or organs, such as CAR-T cells or gene therapy constructs or cells contained therein. As mentioned, exemplary conditions that can be treated therapeutically or prophylactically using the agonist anti-human VISTA antibodies according to the present invention include autoimmune conditions, allergic conditions, inflammatory conditions, GVHD, transplantation, and sepsis. As mentioned, the agonist anti-human VISTA antibodies according to the present invention have been shown to be therapeutically effective and immunosuppressive in a variety of animal disease models, including arthritis, inflammatory bowel disease (IBD), lupus, GVHD, chronic acute infection / hepatotoxicity, and psoriasis disease models. Therefore, the antibodies of the present invention should be well suited for treating conditions where suppressing immunity, especially T cell immunity, is therapeutically desirable. A. Use of agonistic or antagonistic anti-human VISTA antibodies and fragments in therapy and diagnosis The compositions containing agonists according to the present invention can be used to suppress T cell immunity and for treating conditions in which such compositions are beneficial for treatment, such as autoimmune, allergic or inflammatory conditions. Such compositions will include agonist antibodies or antibody fragments according to the present invention in an amount that effectively suppresses T cell activation or proliferation or VISTA's cytokine expression or other effects in a subject in need. Such autoimmune, inflammatory and allergic conditions include, for example, arthritis conditions, such as RA, psoriatic arthritis, psoriasis, scleroderma, multiple sclerosis, lupus, IBD, ITP, diabetes, GVHD, sarcoidosis, allergic asthma, hepatitis-related hepatotoxicity, and are used to suppress T cell immune responses that are not desirable for transplanted cells, tissues or organs, such as CAR-T cells or gene therapy constructs or cells contained therein and their analogs. Specific conditions in which the antibodies of the present invention can be used alone or in combination with other therapeutic agents (particularly other immunosuppressive molecules) include acquired immunodeficiency syndrome (AIDS), acquired splenic atrophy, acute anterior uveitis, acute disseminated encephalomyelitis (ADEM), acute gouty arthritis, acute necrotizing hemorrhagic leukoencephalitis, acute or chronic sinusitis, acute purulent meningitis (or other inflammatory disorders of the central nervous system), acute severe inflammation, Addison's disease ( disease), adrenalitis, adult-onset diabetes mellitus (type 2 diabetes), adult-onset idiopathic hypoparathyroidism (AOIH), agammaglobulinemia, agranulocytosis, vasculitis (including vasculitis, optionally large vessel vasculitis, optionally polymyalgia rheumatica and giant cell (Takayasu's) arthritis), allergic conditions, allergic contact dermatitis, allergic dermatitis, allergic granulomatosis with polyangiitis, allergic hypersensitivity disorders, allergic neuritis, anaphylactic reaction, alopecia areata, alopecia totalis, Alport's syndrome, alveolitis (optionally allergic alveolitis or fibrosing alveolitis), Alzheimer's disease, amyloidosis, amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease), disease), eosinophil-related disorders (optionally eosinophilia), allergic reactions, ankylosing spondylitis, vasodilation, antibody-mediated nephritis, anti-GBM / anti-TBM nephritis, antigen-antibody complex-mediated diseases, anti-glomerular basement membrane disease, antiphospholipid antibody syndrome, antiphospholipid syndrome (APS), aphthous ulcers, aphthous stomatitis, aplastic anemia, cardiac arrhythmias, arteriosclerosis, arteriosclerotic disorders, arthritis (optionally rheumatoid arthritis, such as acute arthritis or chronic rheumatoid arthritis), arthritis chronicaprogrediente), arthritis deformans, ascariasis, aspergilloma, granuloma containing eosinophils, aspergillosis, azoospermia (aspermiogenese), asthma (optionally bronchiolar asthma, bronchial asthma, or autoimmune asthma), telangiectasia, ataxia, atherosclerosis, autism, autoimmune angioedema, autoimmune aplastic anemia, autoimmune atrophic gastritis, autoimmune diabetes mellitus, autoimmune diseases of the testicles and ovary (including autoimmune orchitis and oophoritis), autoimmune disorders associated with collagen diseases, autoimmune autonomic nervous system disorders, autoimmune ear diseases (optionally autoimmune inner ear disease (A GED), autoimmune endocrine diseases (including thyroiditis such as autoimmune thyroiditis), autoimmune enteropathy syndrome, autoimmune glandular failure, autoimmune hearing loss, autoimmune hemolytic reaction, autoimmune hepatitis, autoimmune liver disease, autoimmune hyperlipidemia, autoimmune immune deficiency, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune neutropenia, autoimmune pancreatitis, autoimmune polyendocrinopathy, autoimmune type I polyglandular syndrome, autoimmune retinopathy, autoimmune thrombocytopenic purpura (ATP), autoimmune thyroid disease, autoimmune urticaria, autoimmune-mediated gastrointestinal diseases, axonal and neuronal neuropathies, Barlow's disease disease), Behçet's disease, benign familial and ischemic reperfusion injury, benign lymphocytic vasculitis, Berger's disease (IgA nephropathy), bird breeder's lung, blindness, Boeck's disease, bronchiolitis obliterans (non-transplant) associated with NSIP, bronchitis, bronchopulmonary aspergillosis, Bruton's syndrome, bullous pemphigoid, Caplan's syndrome, cardiomyopathy, cardiovascular ischemia, Castleman's syndrome, celiac disease, sprue (gluten enteropathy), cerebellar degeneration, cerebral ischemia and associated vascular disease, Chagas diseasedisease), channelopathies (optionally epilepsy, CNS channelopathies), chorioretinitis, choroiditis, autoimmune blood diseases, chronic active hepatitis or autoimmune chronic active hepatitis, chronic contact dermatitis, chronic eosinophilic pneumonia, chronic fatigue syndrome, chronic hepatitis, chronic hypersensitivity pneumonitis, chronic inflammatory arthritis, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic refractory inflammation, chronic mucocutaneous candidiasis, chronic neuropathy, optionally IgM polyneuropathy or IgM-mediated neuropathy, chronic obstructive airway disease, chronic inflammatory lung disease, chronic relapsing multifocal osteomyelitis (CRMO), chronic thyroiditis (Hashimoto's thyroiditis) or subacute thyroiditis, Churg-Strauss syndrome syndrome), cicatricial pemphigoid / benign mucous membrane pemphigoid, CNS inflammatory disorders, CNS vasculitis, celiac disease, Cogan's syndrome, cold agglutinin disease, polyposis colitis, colitis (such as ulcerative colitis), colitis ulcerosa, collagenous colitis, conditions involving T-cell infiltration and chronic inflammatory response, congenital heart block, congenital rubella infection, Coombs-positive anemia, coronary artery disease, Coxsackie myocarditis, CREST syndrome (calcification, Raynaud's phenomenon), Crohn's disease, cryoglobulinemia, Cushing's syndrome syndrome), cyclitis (chronic cyclitis, metachronous cyclitis, iridocyclitis, or Fuchs' cyclitis, depending on the context), cystic fibrosis, cytokine-induced toxicity, deafness, degenerative arthritis, demyelinating disease (autoimmune demyelinating disease, demyelinating neuropathy, depending on the context), dengue disease, dermatitis herpetiformis and atopic dermatitis, dermatitis (including contact dermatitis), dermatomyositis, skin diseases with an acute inflammatory component, Devic's disease (neuromyelitis optica), diabetic aorta disease, diabetic nephropathy, diabetic retinopathy, congenital pure red cell aplasia (Diamond Blackfan anemia), diffuse interstitial pulmonary fibrosis, dilated cardiomyopathy, discoid lupus, diseases involving leukocytic diapedesis, Dressler's syndrome, Dupuytren'scontracture), echovirus infection, eczema (including allergic or atopic eczema), encephalitis (such as Rasmussen's encephalitis and limbic and / or brainstem encephalitis), encephalomyelitis (optionally allergic encephalomyelitis or encephalomyelitis allergy and experimental allergic encephalomyelitis (EAE)), intraarterial hyperplasia, endocarditis, endocrine eye disease, endometriosis, endomyocardial fibrosis, endophthalmitis phacoanaphylactica, endophthalmitis, allergic enteritis, eosinophilia-myalgia syndrome, eosinophilic fasciitis, epidemic keratoconjunctivitis, acquired epidermolysis bullosa (EBA), episcleritis, episcleritis, Epstein-Barr virus infection infection), erythema protuberans, erythema multiforme, erythema nodosum leprosum, erythema nodosum, fetal erythroblastosis, esophageal dysmotility, essential mixed cryoglobulinemia, ethmoid bone, Evan's syndrome, experimental allergic encephalomyelitis (EAE), factor VIII deficiency, farmer's lung, fever myalgia, Felty's syndrome, fibromyalgia, fibrosing alveolitis, filariasis, focal segmental glomerulosclerosis (FSGS), food poisoning, forehead, gastric atrophy, giant cell arthritis (temporal arthritis), giant cell hepatitis, giant cell polymyalgia, glomerulonephritis, glomerulonephritis (GN) with and without nephrotic syndromes such as chronic or acute glomerulonephritis (e.g., primary GN), Goodpasture's syndrome syndrome), gouty arthritis, granulomatous transfusion syndrome, granulomatous diseases (including lymphomatoid granulomatosis, granulomatosis with polyangiitis (GPA), and granulomatous uveitis), Grave's disease, Guillain-Barré syndrome, guttate psoriasis, hemoglobinuria paroxysmatica, Hamman-Rich's disease, Hashimoto's disease, Hashimoto's encephalitis, Hashimoto's thyroiditis, hemochromatosis, hemolytic anemia or immune hemolytic anemia (including autoimmune hemolytic anemia (AIHA)), hemolytic anemia, hemophilia A, Henoch-Schönlein purpurapurpura), herpes gestationis, human immunodeficiency virus (HIV) infection, hyperalgesia, hypogammaglobulinemia, hypogonadism, hypoparathyroidism, idiopathic diabetes insipidus, idiopathic facial palsy, idiopathic hypothyroidism, idiopathic IgA nephropathy, idiopathic membranous GN or idiopathic membranous nephropathy, idiopathic renal syndrome, idiopathic pulmonary fibrosis, idiopathic sprue, idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, IgE-mediated diseases (as appropriate, anaphylaxis and allergic or atopic rhinitis), IgG4-related sclerosis, regional ileitis, immune complex nephritis, immune reactions associated with acute and delayed hypersensitivity mediated by cytokines and T-lymphocytes , immune-mediated GN, immunomodulatory lipoproteins (including adult-onset or acute respiratory distress syndrome (ARDS)), inclusion body myositis, infectious arthritis, infertility due to antisperm antibodies, inflammation of the entire or partial uveal tract, inflammatory bowel disease (IBD), inflammatory hyperproliferative skin diseases, inflammatory myopathy, insulin-dependent diabetes mellitus (type 1), insulitis, interstitial cystitis, interstitial lung disease, interstitial pulmonary fibrosis, iritis, ischemic reperfusion syndrome, arthritis, juvenile arthritis, juvenile dermatomyositis, juvenile diabetes mellitus, juvenile-onset (type 1) diabetes mellitus (including insulin-dependent diabetes mellitus (IDDM) in children), juvenile-onset rheumatoid arthritis, Kawasaki syndrome syndrome), keratoconjunctivitis sicca, kypanosomiasis, Lambert-Eaton syndrome, leishmaniasis, leprosy, leukopenia, leukocyte adhesion deficiency, leukocytoclastic vasculitis, leukopenia, lichen planus, lichen sclerosus, woody conjunctivitis, linear IgA dermatosis, linear IgA disease (LAD), Loffler's syndrome, lupus hepatitis, lupus (including nephritis, encephalitis, pediatric, nonrenal, extrarenal, discoid, and alopecia), systemic lupus erythematosus (SLE), disseminated lupus erythematosus, Lyme arthritis, Lyme disease, lymphocytic interstitial pneumonia, malaria, male and female autoimmune infertility, maxillary, medium-vessel vasculitis (including Kawasaki disease and polyarteritis nodosa), membranous or membranous proliferative glomerulonephritis (MPGN) (including types I and II and rapidly progressive GN), membranous GN (membranous nephropathy), Meniere's disease, meningitis, microscopic colitis, microscopic polyangiitis, migraine, minimal change disease, mixed connective tissue disease (MCTD), infectious mononucleosis, Mooren's corneal ulcerulcer), Mucha-Habermann disease, multifocal motor neuropathy, multiple endocrine insufficiency, multiple organ injury syndrome (such as those secondary to sepsis, trauma, or hemorrhage), multiple organ injury syndrome, multiple sclerosis (MS) (such as spinal-ocular MS), multiple sclerosis, mumps, muscle disorders, myasthenia gravis (such as thymoma-associated myasthenia gravis), myasthenia gravis, myocarditis, myositis, narcolepsy, necrotizing enterocolitis and transmural colitis and autoimmune inflammatory bowel disease, necrotizing, cutaneous, or allergic vasculitis, neonatal lupus erythematosus (NLE), renal nephrotic syndrome, neuropathy, neuromyelitis optica (Devic's disease), neuromyelitis optica, neuromyotonia, neutropenia, noncancerous lymphocytosis, nongranulomatous uveitis, nonmalignant thymoma, inflammatory conditions of the eye and orbit, ocular cicatricial pemphigoid, oophoritis, sympathetic ophthalmia, opsoclonus-myoclonus syndrome (OMS), opsoclonus or opsoclonus-myoclonus syndrome (OMS) and sensory neuropathy, optic neuritis or granulomatous cheilitis, osteoarthritis, relapsing rheumatic disease, pancreatitis, pancytopenia, PANDAS (a pediatric autoimmune neuropsychiatric disorder associated with streptococci), paraplastic cerebellar degeneration, paraplastic syndrome, paraplastic syndrome (including neurologic paraplastic syndromes, Lambert-Eaton myasthenic syndrome or Eaton-Lambert syndrome, as appropriate), parasitic diseases (such as leishmaniasis), paroxysmal nocturnal hemoglobinuria (PNH), Parry-Romberg syndrome, pars planitis (peripheral uveitis), Parsonnage-Turner syndrome syndrome), parvovirus infection, pemphigoid (such as bullous pemphigoid and cutaneous pemphigoid), pemphigus (including pemphigus vulgaris), pemphigus erythematosus, pemphigus foliaceus, pemphigus mucomembranous pemphigoid, pemphigus, peptic ulcer, periodic paralysis, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia / anemia perniciosa), pernicious anemia, lens antigen uveitis, cirrhosis, POEMS syndrome, polyarteritis nodosa (types I, II, and III), primary chronic polyarthritis, polychondritis (e.g., refractory or relapsing polychondritis), polyendocrine autoimmune disease, polyendocrine insufficiency, polyglandular syndrome (optionally, autoimmune polyglandular syndrome (or polyglandular endocrine disorder syndrome), polymyalgia rheumatica, polymyositis, polymyositis / dermatomyositis, polyneuropathy, acute polyradiculitisacuta), postcardiotomy syndrome, posterior uveitis or autoimmune uveitis, post-myocardial infarction syndrome, postpericardiotomy syndrome, poststreptococcal nephritis, postvaccination syndrome, Alzheimer's disease, primary biliary cirrhosis, primary hypothyroidism, primary idiopathic mucinous adenoma, primary lymphocytosis (including monoclonal B-cell lymphocytosis, optionally benign monoclonal gammopathy, and monoclonal gammopathy of undetermined significance), MGUS, primary mucinous adenoma, primary progressive MS (PPMS), and relapsing-remitting MS (RRMS), primary sclerosing cholangitis, progesterone-induced dermatitis, progressive systemic sclerosis, proliferative arthritis, psoriasis (such as plaque psoriasis), psoriasis, psoriatic arthritis, pulmonary alveolar proteinosis, pulmonary infiltrate with eosinophilia, pure red cell anemia or aplasia (PRCA), pure red cell aplasia, suppurative or non-purulent sinusitis, pustular psoriasis and nail psoriasis, pyelitis, pyoderma gangrenosum, Quervain's thyroiditis, Raynaud's phenomenon, reactive arthritis, recurrent miscarriage, hypotensive reflexia, sympathetic dysreflexia, refractory sprue, Reiter's disease or syndrome syndrome), relapsing polychondritis, myocardial or other tissue reperfusion injury, reperfusion injury, respiratory distress syndrome, restless legs syndrome, retinal autoimmunity, retroperitoneal fibrosis, Raynaud's syndrome, rheumatic diseases, rheumatic fever, rheumatism, rheumatoid arthritis, rheumatoid spondylitis, rubella virus infection, Sampter's syndrome, sarcoidosis, schistosomiasis, Schmidt syndrome, SCID and Epstein-Barr virus-associated disease, sclerosis, scleritis, digital scleroderma, scleroderma (optionally systemic scleroderma), sclerosing cholangitis, disseminated sclerosis, sclerosis (such as systemic sclerosis), sensorineural hearing loss, blood-negative spondyloarthropathy, Sheehan's syndrome, Shulman's syndrome syndrome), silicosis, Sjögren's syndrome, semen and testicular autoimmunity, sphenoid sinusitis, Stevens-Johnson syndrome, stiff-man or stiff-person syndrome, subacute bacterial endocarditis (SBE), subacute cutaneous lupus erythematosus, sudden hearing loss, Susac's syndrome, Sydenham's choreachorea), sympathetic ophthalmia, systemic lupus erythematosus (SLE) or systemic lupus erythematodes, cutaneous SLE, systemic necrotizing vasculitis, ANCA-associated vasculitis (Czag-Strauss vasculitis or syndrome (CSS) as appropriate), tabes dorsalis, Takayasu's arteritis, telangiectasia, temporal arteritis / giant cell arteritis, thromboangiitis obliterans, thrombocytopenia (including thrombotic thrombocytopenic purpura (TTP) and autoimmune or immune-mediated thrombocytopenia, such as idiopathic thrombocytopenic purpura (ITP), including chronic or acute ITP and thrombocytopenic purpura (TTP)), thyrotoxicosis, tissue injury, Tolosa-Hunt syndrome (TLP), and other inflammatory bowel diseases. syndrome), toxic epidermal necrolysis, toxic shock syndrome, transfusion reaction, transient hypogammaglobulinemia of infancy, transverse myelitis (traverse myelitis), tropical pulmonary eosinophilia, pulmonary tuberculosis, ulcerative colitis, undifferentiated connective tissue disease (UCTD), urticaria (chronic allergic urticaria and chronic idiopathic urticaria, including chronic autoimmune urticaria, as appropriate), uveitis, anterior uveitis, uveoretinitis, valvulitis, vascular dysfunction, vasculitis, vertebral osteoarthritis, cystic dermatosis, vitiligo, Wegener's granulomatosis (granulomatosis with polyangiitis (GPA)), Wiskott-Aldrich syndrome, or X-linked hyper-IgM syndrome. In contrast, compositions containing VISTA antagonist antibodies according to the present invention can be used to promote T cell immunity and treat conditions in which such compositions are beneficial, such as cancer and infectious conditions, such as viral, bacterial, yeast, fungal, protozoan and parasitic infections. Such compositions will contain an antagonist according to the present invention in an amount effective to promote T cell activation or proliferation or cytokine expression or other effects of VISTA in a subject in need. Such cancer conditions include, for example, blood cancers and solid tumors, such as leukemia, lymphoma, myelodysplasia syndrome, myeloma, lung cancer, and other cancers identified herein. It is to be understood that the disease states identified herein are intended to be illustrative and not exhaustive. The agonists and antagonists of the present invention may be combined with other therapeutic agents that may be administered at the same or different times in the same or different compositions. For example, the agonists of the present invention may be administered in a treatment regimen that includes administration of a PD-1 or PD-L1 agonist, CTLA4-Ig, a cytokine, a cytokine agonist or antagonist, or another receptor agonist or antagonist. Raising or enhancing the inhibitory function of the VISTA polypeptide can be used to lower the immune response. Lowering can be in the form of suppressing or blocking an immune response already in development, or can encompass preventing the induction of an immune response. The function of activated immune cells can be suppressed by lowering the immune cell response or by inducing specific anergy in immune cells or by these two ways. For example, a VISTA agonist antibody can bind to the VISTA polypeptide expressed on various immune cells and thereby lower the immune response. This agonist antibody can be monospecific or multispecific, for example, it can include a bispecific antibody, such as BiTE. For example, such an antibody can include a VISTA antigen binding portion and another antigen binding portion, such as an antigen binding portion of a cell surface receptor on a target immune cell (e.g., a T cell, a B cell, or a bone marrow cell). In addition to comprising a VISTA antigen binding site, such an antibody can include a binding site that binds to a B cell antigen receptor, a T cell antigen receptor, or an Fc or other receptor, thereby targeting the molecule to a specific cell population. Selecting this second antigen for a bispecific antibody provides flexibility in selecting a cell population to be targeted. VISTA agonist antibodies that promote or mimic VISTA activity can enhance the interaction between VISTA and its natural binding partners. As disclosed herein, other human VISTA activating or agonist antibodies can be identified by their ability to inhibit T cell activity or proliferation and / or based on their in vitro immunosuppressive effects or inflammatory, allergic, or autoimmune disease models. A variety of cell activation readings identified in this technology can be used to measure, for example, cell proliferation or effector function (e.g., antibody production, cytokine production, phagocytosis) in the presence of an activator. The ability of the test antibody to stimulate or promote the effect of human VISTA and thus block this activation can be easily determined by measuring the ability of the agent to affect the measured proliferation or effector function reduction. Therefore, the ability of the test antibody to have immunosuppressive properties and to block immune activation can be determined by measuring cytokine production and / or proliferation at different concentrations of antigen. Tolerance to specific antigens can be induced by co-administering an antigen with a VISTA agonist antibody according to the present invention. For example, tolerance to the immune response of a specific polypeptide to an allergen or foreign polypeptide can be induced, and an adverse immune response can be suppressed. For example, patients receiving factor VIII often produce antibodies against this coagulation factor. Co-administration of a VISTA agonist antibody that stimulates or simulates VISTA activity or interacts with its natural binding partner according to the present invention with recombinant factor VIII can suppress this adverse immune response. The VISTA agonist antibodies according to the present invention can be used in combination with another agent that blocks the activity of a co-stimulatory receptor on immune cells or agonizes the activity of another immunosuppressive receptor or ligand expressed on immune cells to downregulate the immune response. Exemplary molecules include: PD-1, PDL-1 agonists, soluble forms of CTLA-4, anti-B7-1 antibodies, anti-B7-2 antibodies, antagonistic antibodies targeting one or more of LAG-3, TIM-3, BTLA, B7-H4, B7H3, etc., and / or agonistic antibodies targeting one or more of CD40, CD137, OX40, GITR, CD27, CD28, or ICOS, or a combination thereof. These moieties can be combined in a single composition or compound, such as a bispecific antibody containing a VISTA agonist antibody according to the present invention and further comprising another immunosuppressive antibody, or a fusion polypeptide containing a VISTA agonist antibody according to the present invention fused to another immunosuppressive polypeptide or other active agent. Alternatively, the moieties may be administered as separate or discrete entities (simultaneously or sequentially) in the same or different compositions to downregulate an immune response mediated by immune cells in a subject. Examples of specific immunosuppressive molecules that can be combined with the VISTA agonist antibodies according to the present invention include antibodies that block co-stimulatory signals (e.g., against CD28 or ICOS), antibodies that inhibit signals through CTLA4 activation and / or antibodies against other immune cell markers (e.g., against CD40, CD40 ligand or cytokines), fusion proteins (e.g., CTLA4-Fc or PD-1-Fc), and immunosuppressive drugs (e.g., rapamycin, cyclosporine A or FK506). In another embodiment, the bispecific antibody containing the VISTA agonist antibody according to the present invention is suitable for targeting specific cell populations, for example, using markers found only on certain types of cells (such as B lymphocytes, monocytes, dendritic cells or Langerhans cells). By activating VISTA activity or VISTA-immune cell interactions to downregulate the immune response (and thus stimulate the negative signal transduction function of VISTA), it is suitable for, for example, tissue, skin and organ transplantation, in graft-versus-host disease (GVHD) or allergies or in the case of autoimmune and inflammatory diseases such as systemic lupus erythematosus, IBD, RA, psoriasis and multiple sclerosis to downregulate the immune response. For example, blocking immune cell function leads to reduced tissue destruction in tissue transplantation. Typically in tissue transplantation, it is recognized as a foreigner by immune cells and causes the rejection of the transplant, followed by the immune response that destroys the transplant. Before transplantation or during transplantation, alone or in combination with another downregulator, the molecule that promotes the activity of VISTA or the interaction of VISTA with its natural binding partner can suppress the generation of costimulatory signals. Furthermore, boosting VISTA activity may be sufficient to provide energy to immune cells, thereby inducing tolerance in the subject. In order to achieve adequate immunosuppression or tolerance in certain diseases or certain subjects, it is necessary to block the co-stimulatory function of other molecules. For example, it may be necessary to block the function of B7-1 and B7-2 by administering a soluble form of a peptide combination before or at the time of transplantation, wherein the peptide combination has the activity of these antigens or blocking antibodies against each of these antigens (alone or together in a single composition). Alternatively, it may be necessary to promote the inhibitory activity of VISTA and further inhibit the co-stimulatory activity of B7-1 and / or B7-2. The anti-human VISTA agonist antibodies of the present invention are particularly suitable for treating autoimmune diseases. Many autoimmune disorders are the result of improper activation of immune cells that are reactive against their own tissues and promote the production of cytokines and autoantibodies involved in the pathology of the disease. Preventing the activation of autoreactive immune cells can reduce or eliminate disease symptoms. Administration of anti-human VISTA agonist antibodies that promote VISTA activity or the interaction of VISTA with its natural binding partner of the present invention can induce antigen-specific tolerance of autoreactive immune cells, which can lead to long-term relief of the disease. In addition, co-administration of agents and co-stimulatory receptors that block immune cell co-stimulation by destroying the receptor-ligand interaction of B7 molecules can be used to inhibit immune cell activation, thereby preventing the production of autoantibodies or cytokines that may be involved in the disease process. Downregulating the immune response by stimulating VISTA activity or the interaction of VISTA with its natural binding partner using the anti-human VISTA agonist antibodies of the present invention may also be applicable to the treatment of autoimmune invasion of autologous tissues. Thus, conditions caused or exacerbated by autoimmune invasion (e.g., heart disease, myocardial infarction, or atherosclerosis) can be improved or modified by increasing VISTA activity or the binding of VISTA to its natural binding partner. Therefore, it is within the scope of the present invention to regulate conditions exacerbated by autoimmune invasion, such as autoimmune disorders (as well as conditions such as heart disease, myocardial infarction, and atherosclerosis) by using the anti-human VISTA agonist antibodies of the present invention to stimulate VISTA activity or the interaction of VISTA with its anti-receptors. As mentioned above, the efficacy of the agonist anti-human VISTA antibodies according to the present invention for preventing or alleviating autoimmune and inflammatory disorders can be determined using a variety of well-characterized animal models of human autoimmune and inflammatory diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythematosus in MRL / lpr / lpr mice or NZB heterozygous mice, murine autoimmune collagen arthritis, diabetes in NOD mice and BB rats, and murine experimental myasthenia gravis. See Paul, ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 840–856. Inhibiting immune cell activation is further therapeutically useful for treating allergies and allergic reactions, for example by inhibiting IgE production. The anti-human VISTA agonist antibodies of the present invention that promote or simulate VISTA activity or the interaction between VISTA and its natural binding partner can be administered to allergic subjects to inhibit allergic reactions mediated by immune cells in the subject. Stimulating VISTA activity or interaction with its natural binding partner can be accompanied by exposure to allergens and appropriate MHC molecules. Depending on the entry route of the allergen and the deposition pattern of IgE on mast cells or basophils, allergic reactions can be systemic or local in nature. Therefore, immune cell-mediated allergic reactions can be suppressed locally or systemically by administering anti-human VISTA agonist antibodies of the present invention. Select anti-VISTA antibodies that bind to the same antigenic determinant In certain embodiments, the agonistic anti-VISTA antibodies according to the present invention have the desired functional properties, such as regulating immune stimulation and related functions. As shown in Figure 4 and disclosed in the operating examples, the antigenic determinant specificity of a variety of anti-human VISTA agonist antibodies according to the present invention has been illustrated. Since it has been found that a variety of antibodies showing binding to the same antigenic determinant have immunosuppression, it is expected that other VISTA agonist antibodies can be identified that are bound to the same or overlapping antigenic determinants, that is, they will interact with one or more of the amino acid residues of the human VISTA polypeptides bound by the exemplary VISTA agonist antibodies. Other antibodies with the same antigenic determinant specificity and / or those antibodies with the ability to cross-compete with the desired antibody to bind to the VISTA antigen can be selected. For example, overlapping peptide libraries comprising complete VISTA polypeptides (e.g., 15 polymers) or overlapping peptide libraries constituting a portion of the desired antigenic determinant containing VISTA can be used to determine the antigenic determinant specificity of the desired antibody, and antibodies bound to the same peptide or one or more residues thereof in the library are determined to be bound to the same linear or conformational antigenic determinants. In one embodiment, Pepscan, which can recognize linear and conformational epitopes, was used. ® Methods for determining antigenic determinant specificity. Modification of agonist antibodies according to the present invention In addition or as an alternative to modifications made within the framework or CDR regions, antibodies according to at least some embodiments of the present invention may be engineered to include modifications within the Fc region, typically to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding, and / or antigen-dependent cellular cytotoxicity. In addition, antibodies according to at least some embodiments of the present invention may be chemically modified (e.g., one or more chemical moieties may be attached to the antibody) or modified to alter their glycosylation, again altering one or more functional properties of the antibody. Such embodiments are further described below. The residue numbering in the Fc region is that of the EU index of Kabat. In one embodiment, the hinge region of CHI is modified such that the number of cysteine ​​residues in the hinge region is altered, for example, increased or decreased. This approach is further described by Bodmer et al. in U.S. Patent No. 5,677,425. The number of cysteine ​​residues in the hinge region of CHI is altered to, for example, facilitate assembly of the light and heavy chains or to increase or decrease antibody stability. In another embodiment, the Fc hinge region of an antibody is mutated to reduce the biological half-life of the antibody. More specifically, one or more amino acid mutations are introduced into the CH2-CH3 domain interface of the Fc-hinge fragment to render the antibody impaired in Staphylococcal protein A (SpA) binding relative to SpA binding by the native Fc-hinge domain. This approach is further described in detail by Ward et al. in U.S. Patent No. 6,165,745. In another embodiment, the antibody is modified to increase its biological half-life. Various methods are possible. For example, one or more of the following mutations can be introduced: T252L, T254S, and T256F as described by Ward in U.S. Patent No. 6,277,375. Alternatively, to increase biological half-life, the antibody in the CHI or CL region can be altered to contain salvage receptor binding epitopes from two loops of the CH2 domain of the Fc region of IgG, as described by Presta et al. in U.S. Patent Nos. 5,869,046 and 6,121,022. In yet other embodiments, the Fc region is altered by replacing at least one amino acid residue with a different amino acid residue, thereby altering the effector function of the antibody. For example, one or more amino acids selected from amino acid residues 234, 235, 236, 237, 297, 318, 320, and 322 can be replaced with a different amino acid residue to alter the antibody's affinity for an effector ligand while retaining the antigen-binding ability of the parent antibody. The effector ligand with altered affinity can, for example, be an Fc receptor or the C1 component of complement. This method is further described in detail by Winter et al. in U.S. Patent Nos. 5,624,821 and 5,648,260. In another example, one or more amino acids selected from amino acid residues 329, 331, and 322 can be substituted with different amino acid residues to result in an antibody with altered C1q binding and / or reduced or abolished complement-dependent cytotoxicity (CDC). This approach is described in further detail by Idusogie et al., U.S. Patent No. 6,194,551. In another example, one or more of amino acid residues at amino acid positions 231 and 239 can be altered to thereby alter the ability of the antibody to fix complement. This approach is further described by Bodmer et al. in PCT Publication WO 94 / 29351. In another example, the Fc region is modified to increase the affinity of the antibody for the Fγ receptor by modifying one or more amino acids at the following positions: 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296 , 298, 301, 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, ​​388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439. This approach is further described by Presta in PCT publication WO 00 / 42072. In addition, the binding sites on human IgG1 for FcγRI, FcγRII, FcγRIII and FcRn have been mapped and variants with improved binding have been described (see Shields, RL et al. (2001)). J. Biol. Chem. 276:6591-6604). Specific mutations at positions 256, 290, 298, 333, 334, and 339 showed improved binding to FcγRIII. In addition, the following combination mutants showed improved FcγRIII binding: T256A / S298A, S298A / E333A, S298A / K224A, and S298A / E333A / K334A. Furthermore, mutations such as M252Y / S254T / T256E or M428L / N434S improved binding to FcRn and increased antibody circulation half-life (see Chan CA and Carter PJ (2010)). Nature Rev Immunol 10:301-316). In another embodiment, antibodies can be modified to eliminate in vivo Fab arm exchange. Specifically, this process encompasses the exchange of IgG4 half molecules (one heavy chain plus one light chain) between other IgG4 antibodies, which effectively generates functional monovalent b-specific antibodies. Mutations in the hinge region and constant domains of the heavy chain can eliminate this exchange (see Aalberse, RC, Schuurman J., 2002, Immunology 105:9-19). In another embodiment, the glycosylation of the antibody is modified. For example, an aglycosylated antibody (i.e., an antibody lacking glycosylation) can be produced. Glycosylation can be altered to, for example, increase the affinity of the antibody for the antigen. Such carbohydrate modifications can be achieved, for example, by changing one or more glycosylation sites within the antibody sequence. For example, one or more amino acid substitutions can be made, resulting in the elimination of one or more variable region framework glycosylation sites, thereby eliminating glycosylation at this site. This aglycosylation effect can increase the affinity of the antibody for the antigen. This method is further described in detail by Co et al. in U.S. Patent Nos. 5,714,350 and 6,350,861. Additionally or alternatively, antibodies with altered types of glycosylation can be produced, such as hypofucosylated antibodies with a reduced amount of fucosyl residues or antibodies with an increase in bisecting GlcNac structures. Such altered glycosylation patterns have been shown to increase the ADCC ability of antibodies. Such carbohydrate modifications can be achieved, for example, by expressing the antibody in a host cell with an altered glycosylation machinery. Cells with altered glycosylation machinery have been described in the art and can be used as host cells in which to express recombinant antibodies according to at least some embodiments of the present invention to produce antibodies with altered glycosylation. For example, cell lines Ms704, Ms705, and Ms709 lack the fucosyltransferase gene FUT8 (a (1,6) fucosyltransferase), such that antibodies expressed in Ms704, Ms705, and Ms709 cell lines lack fucose on their carbohydrates. Ms704, Ms705, and Ms709 FUT8 cell lines were generated by targeted disruption of the FUT8 gene in CHO / DG44 cells using two replacement vectors (see U.S. Patent Publication No. 20040110704 by Yamane et al. and Yamane-Ohnuki et al. (2004)). Biotechnol Bioeng 87:614-22). As another example, EP 1,176,195 by Hanai et al. describes a cell line with a functionally disrupted FUT8 gene encoding a fucosyltransferase, such that antibodies expressed in the cell line exhibit hypofucosylation by reducing or eliminating the 1,6-linked enzyme. Hanai et al. also describe cell lines that have low or no enzymatic activity for the addition of fucose to N-acetylglucosamine bound to the Fc region of an antibody, such as the rat myeloma cell line YB2 / 0 (ATCC CRL 1662). PCT publication WO 03 / 035835 by Presta describes a variant CHO cell line, Lec13 cells, that has reduced ability to attach fucose to Asn(297)-linked carbohydrates, also resulting in hypofucosylation of antibodies expressed in this host cell (see also Shields, RL et al. (2002)). J. Biol. Chem. 277:26733-26740). PCT Publication WO 99 / 54342 by Umana et al. describes a cell line engineered to express a glycosyltransferase that modifies glycoproteins, such as β(1,4)-N-acetylglucosaminyltransferase III (GnTIII), such that antibodies expressed in the engineered cell line display increased bisecting GlcNac structures, which results in increased ADCC activity of the antibody (see also Umana et al. (1999)). Nat. Biotech. 17: 176-180). Alternatively, fucosidase can be used to cleave the fucose residues of the antibody. For example, fucosidase α-L-fucosidase removes fucosyl residues from antibodies (Tarentino, AL et al. (1975) Biochem. 14: 5516-23). Another modification of antibodies herein encompassed by the present invention is pegylation or the addition of other water-soluble moieties (typically polymers), for example to enhance half-life. Antibodies can be pegylated to, for example, increase the biological (e.g., serum) half-life of the antibody. To pegylate an antibody, the antibody or fragment thereof is typically reacted with polyethylene glycol (PEG), such as a reactive ester or aldehyde derivative of PEG, under conditions where one or more PEG groups are attached to the antibody or antibody fragment. Pegylation is preferably performed via an acylation reaction or an alkylation reaction with a reactive PEG molecule (or a similar reactive water-soluble polymer). As used herein, the term "polyethylene glycol" is intended to encompass any form of PEG that has been used to derivatize other proteins, such as mono(Ci-Cio)alkoxy- or aryloxy-polyethylene glycol or polyethylene glycol-maleimide. In certain embodiments, the antibody to be pegylated is a non-glycosylated antibody. Methods for pegylation of proteins are known in the art and can be applied to antibodies according to at least some embodiments of the present invention. See, for example, EP 0 154 316 by Nishimura et al. and EP 0 401 384 by Ishikawa et al. Methods of Engineering Antibodies In certain embodiments, the invention has V H and V L Agonist anti-VISTA antibodies can be modified by modifying V H and / or V LSequence or constant region connected thereto and be used to produce new anti-VISTA antibodies respectively. Therefore, in another aspect according to at least some embodiments of the present invention, the structural features of the anti-VISTA antibodies according to at least some embodiments of the present invention are used to produce structurally related anti-VISTA antibodies that retain at least one functional characteristic of the antibody according to at least some embodiments of the present invention (such as binding to human VISTA). For example, as discussed above, one or more CDR regions of a VISTA antibody or a mutation thereof can be recombined with known framework regions and / or other CDRs to produce other recombinantly engineered anti-VISTA antibodies according to at least some embodiments of the present invention. Other types of modifications include those described in the aforementioned sections. The starting material for the engineering method is V provided herein. H and / or V L To generate an engineered antibody, it is not necessary to actually prepare (i.e., express as a protein) a V sequence as provided herein. H and / or V L Instead, the information contained in the sequence is used as starting material to generate "second generation" sequences derived from the initial sequence, and these "second generation" sequences are subsequently prepared and expressed as proteins. Standard molecular biology techniques can be used to prepare and express the altered antibody sequences. The anti-VISTA antibodies encoded by the altered antibody sequences are preferably antibodies that retain one, some or all of the functional properties of the anti-VISTA antibodies produced by the methods herein and having the sequences provided herein, including specific K D Level or below this K D The invention relates to a method for selectively binding to a VISTA antigen and / or modulating an immune response and / or selectively binding to a desired target cell expressing a VISTA antigen. The functional properties of the altered antibodies can be assessed using standard assays available in the art and / or described herein. In certain embodiments of the methods of engineering antibodies according to at least some embodiments of the present invention, mutations can be introduced randomly or selectively along with all or part of the anti-VISTA antibody coding sequence, and the resulting modified anti-VISTA antibodies can be screened for binding activity and / or other desired functional properties. Mutation methods have been described in the art. For example, PCT Publication WO 02 / 092780 by Short describes methods for generating and screening antibody mutations using saturation mutagenesis, synthetic ligation assembly, or a combination thereof. Alternatively, PCT Publication WO 03 / 074679 by Lazar et al. describes methods for optimizing the physicochemical properties of antibodies using computer screening methods. Nucleic acid molecules encoding antibodies The present invention further provides nucleic acids encoding anti-VISTA antibodies according to the present invention, or fragments thereof, or conjugates thereof. Such nucleic acids may be present in intact cells, cell lysates, or in partially purified or substantially pure form. Nucleic acids are “isolated” or “rendered substantially pure” when purified to remove other cellular components or other contaminants (e.g., other cellular nucleic acids or proteins) by standard techniques, including alkali / SDS treatment, CsCl banding, column chromatography, agarose gel electrophoresis, and other techniques well known in the art. See F. Ausubel et al. (1987). Current Protocols in Molecular Biology, Greene Publishing and Wiley Interscience, New York. Nucleic acids according to at least some embodiments of the present invention can be, for example, DNA or RNA, and may or may not contain intronic sequences. In a preferred embodiment, the nucleic acid is a cDNA molecule. Nucleic acids according to at least some embodiments of the present invention can be obtained using standard molecular biology techniques. For antibodies expressed by hybridomas (e.g., hybridomas produced from transgenic mice carrying human immunoglobulin genes, as further described below), cDNAs encoding the light and heavy chains of the antibodies produced by the hybridomas can be obtained by standard PCR amplification or cDNA cloning techniques. For antibodies obtained from an immunoglobulin gene library (e.g., using phage display technology), nucleic acids encoding the antibodies can be recovered from the library. Once the code V is obtained H and V L The DNA fragments of the segment can be further manipulated by standard recombinant DNA technology, for example, to convert the variable region gene into a full-length antibody chain gene, into a Fab fragment gene, or into a scFv gene. L - or V H- A DNA fragment encoding a protein is operably linked to another DNA fragment encoding another protein, such as an antibody constant region or a flexible linker. As defined above, "operably linked" means that the two DNA fragments are joined so that the amino acid sequences encoded by the two DNA fragments remain in frame. By encoding V H The DNA encoding the heavy chain constant region (CH1, CH2 and CH3) can be operably linked to another DNA molecule encoding the V H The isolated DNA of the heavy chain constant region is converted into full-length heavy chain genes. The sequences of human heavy chain constant region genes are known in the art (see, e.g., Kabat, EA et al. (1991)). Sequences of Proteins of Immunological Interest, 5th Edition, US Department of Health and Human Services, NIH Publication No. 91-3242) and DNA fragments comprising these regions can be obtained by standard PCR amplification. The heavy chain constant region can be IgG1, IgG2, IgG3, IgG4, IgA, IgE, IgM, or IgD constant region, but is most preferably IgG1, IgG2, or IgG4 constant region. For the Fab fragment heavy chain gene, the VH encoding DNA can be operably linked to a heavy chain C encoding only DNA fragment. H1 Another DNA molecule containing the constant region. By encoding V L The DNA encoding the V constant region can be operably linked to another DNA molecule encoding the light chain constant region to L The isolated DNA of the region was converted into full-length light chain gene (and Fab light chain gene), human light chain constant region gene C L - sequences are known in the art (see, e.g., Kabat, EA et al. (1991) Sequences of Proteins of Immunological Interest, 5th Edition, US Department of Health and Human Services, NIH Publication No. 91-3242) and DNA fragments comprising these regions can be obtained by standard PCR amplification. The light chain constant region can be a kappa or lambda constant region, but is most preferably a kappa constant region. To generate scFv genes, the V H and V L The DNA fragment encoding the flexible linker can be operably linked to another fragment encoding the amino acid sequence (eg, (Gly4-Ser)3) so that V H and V L The sequence can be expressed as a continuous single-chain protein, in which V L With V H The regions are joined by a flexible linker (see, e.g., Bird et al. (1988) Science 242:423-426; Huston et al. (1988) Proc. Natl. Acad. Sci., USA85:5879-5883; McCafferty et al. (1990) Nature 348:552-554). Production of anti-VISTA monoclonal antibodies Anti-VISTA monoclonal antibodies (mAbs) and antigen-binding fragments according to the present invention can be produced by various techniques, including conventional monoclonal antibody methods, such as the standard somatic cell hybridization technique of Kohler and Milstein (1975). Nature 256: 495. Although somatic cell hybridization procedures are preferred, other techniques for generating monoclonal antibodies can in principle be employed, such as viral or oncogenic transformation of B lymphocytes. A preferred animal system for preparing fusion tumors is the murine system. Producing fusion tumors in mice is a very complete procedure. Immunological experimental protocols and techniques for isolating immune spleen cells for fusion are known in the art. Fusion partners (e.g., murine myeloma cells) and fusion procedures are also known. Chimeric or humanized antibodies of the present invention can be prepared based on the sequence of the murine monoclonal antibody prepared as described above. DNA encoding heavy and light chain immunoglobulins can be obtained from the murine fusion tumor of interest using standard molecular biological techniques and engineered to contain non-murine (e.g., human) immunoglobulin sequences. For example, to produce chimeric antibodies, murine variable regions can be linked to human constant regions using methods known in the art (see, e.g., U.S. Patent No. 4,816,567 to Cabilly et al.). To create humanized antibodies, the murine CDR regions can be inserted into a human framework using methods known in the art (see, e.g., U.S. Pat. No. 5,225,539 to Winter and U.S. Pat. Nos. 5,530,101, 5,585,089, 5,693,762, and 6,180,370 to Queen et al.). According to at least some embodiments of the present invention, the antibodies are human monoclonal antibodies. Such human monoclonal antibodies against VISTA can be produced using transgenic or transchromosomal mice that carry parts of the human immune system rather than the mouse system. Such transgenic and transchromosomal mice include those referred to herein as HuMAb Mouse ™ and KM Mouse ™ HuMAb Mouse ™ (Medarex Inc.) contains a human immunoglobulin gene miniloci encoding unrearranged human heavy μ and gamma and kappa light chain immunoglobulin sequences, and targeted mutations that inactivate the endogenous μ and kappa chain loci (see, e.g., Lonberg et al. (1994) Nature 368(6474): 856-859). As a result, the mice exhibit reduced expression of mouse IgM or κ and respond to immunization with the introduced human heavy and light chain transgenes undergo class switching and somatic mutation to generate high-affinity human IgG κ monoclonals (Lonberg, N. et al. (1994), supra; in Lonberg, N. (1994) Handbook of Experimental Pharmacology 113:49-101; Lonberg, N. and Huszar, D. (1995) Intern. Rev. Immunol. 13: 65-93 and Harding, F. and Lonberg, N. (1995) Ann. NY Acad. Sci. 764:536-546). HuMab Mouse ® The preparation and use of mice and the genetic modification carried by them are described in Taylor, L. et al. (1992) Nucleic Acids Research 20:6287-6295; Chen, J. et al. (1993) International Immunology 5:647-656; Tuaillon et al. (1993) Proc. Natl. Acad. Sci. USA 90:3720-3724; Choi et al. (1993) Nature Genetics 4: 117-123; Chen, J. et al. (1993) EMBO J. 12: 821-830; Tuaillon et al. (1994) J. Immunol. 152:2912-2920; Taylor, L. et al. (1994) International Immunology 6:579-591; and Fishwild, D. et al. (1996) Further described in Nature Biotechnology 14: 845-851, all of which is specifically incorporated herein by reference in its entirety. See further U.S. Patent Nos. 5,545,806, 5,569,825, 5,625,126, 5,633,425, 5,789,650, 5,877,397, 5,661,016, 5,814,318, 5,874,299, and 5,770,429, all to Lonberg and Kay; U.S. Patent No. 5,545,807 to Surani et al.; PCT Publication Nos. WO 92 / 03918, WO 93 / 12227, WO 94 / 25585, WO 97 / 13852, WO 98 / 24884, and WO No. 99 / 45962, all to Lonberg and Kay; and PCT Publication No. WO 01 / 14424 to Korman et al. In another embodiment, mice carrying human immunoglobulin sequences on transgenes and transchromosomes, such as mice carrying a human heavy chain transgene and a human light chain transchromosome, can be used to generate human antibodies according to at least some embodiments of the present invention. ™ Such mice are described in detail in PCT Publication WO 02 / 43478 by Ishida et al. Still further, alternative transgenic animal systems expressing human immunoglobulin genes are available in the art and can be used to produce anti-VISTA antibodies according to at least some embodiments of the present invention. For example, an alternative transgenic system called Xenomouse (Abgenix, Inc.) can be used; such mice are described, for example, in U.S. Patent Nos. 5,939,598, 6,075,181, 6,114,598, 6,150,584, and 6,162,963 to Kucherlapati et al. In addition, alternative transchromosomal animal systems expressing human immunoglobulin genes are available in the art and can be used to generate anti-VISTA antibodies according to at least some embodiments of the present invention. For example, mice carrying human heavy chain transchromosomes and human light chain transchromosomes, referred to as "TC mice," can be used; these mice were described in Tomizuka et al. (2000). Proc. Natl. Acad Sci. USA 97: 722-727. In addition, cows carrying human heavy and light chain transchromosomes have been described in the art (Kuroiwa et al. (2002) Nature Biotechnology 20:889-894) and which can be used to generate anti-VISTA antibodies according to at least some embodiments of the invention. Human monoclonal antibodies according to at least some embodiments of the present invention can also be prepared using phage display methods for screening human immunoglobulin gene libraries. Such phage display methods for isolating human antibodies are well established in the art. See, for example, U.S. Patents 5,223,409, 5,403,484, and 5,571,698 to Ladner et al.; U.S. Patents 5,427,908 and 5,580,717 to Dower et al.; U.S. Patents 5,969,108 and 6,172,197 to McCafferty et al.; and U.S. Patents 5,885,793, 6,521,404, 6,544,731, 6,555,313, 6,582,915, and 6,593,081 to Griffiths et al. Human monoclonal antibodies according to at least some embodiments of the present invention can also be prepared using SCID mice in which human immune cells have been reconstituted so that they can produce a human antibody response upon immunization. Such mice are described, for example, in Wilson et al., U.S. Patent Nos. 5,476,996 and 5,698,767. In some embodiments, as described by Lonberg, N. et al. (1994) Nature 368(6474): 856-859; Fishwild, D. et al. (1996) Nature Biotechnology 14: 845-851; and PCT Publications WO 98 / 24884 and WO 01 / 14424, human Ig mice are used, for example, to produce human anti-VISTA antibodies according to the present invention by immunizing such mice with purified or enriched preparations of VISTA antigen and / or recombinant VISTA or VISTA fusion proteins. After the first infusion, the mice are preferably 6 to 16 weeks old. For example, purified or recombinant preparations of VISTA antigen (dosage range of 0.5 to 500 μg) can be used to immunize human Ig mice intraperitoneally. In general, when the initial antigen in complete Freund's adjuvant (complete Freund's adjuvant) is immunized intraperitoneally (IP), and then every other week with the antigen in incomplete Freund's adjuvant IP immunization (up to a total of 6 times), the transgenic mice react. However, it was found that adjuvants other than Freund's adjuvant are also effective. In addition, it was found that intact cells are highly immunogenic in the absence of adjuvant. During the immune protocol, plasma samples obtained from retroorbital bleeding can be used to manipulate the immune response. Plasma can be screened by ELISA (as described below) and mice with anti-VISTA human immunoglobulins of sufficient titer can be used for fusion. Three days before sacrifice and removal of the spleen, mice can be reinforced with antigens intravenously. It is expected that 2 to 3 fusions may be required for each immunization. For each antigen, mice between 6 and 24 are usually immunized. Two strains, HCo7 and HCo12, are commonly used. Alternatively, the HCo7 and HCo12 transgenes can be bred together into a single mouse with two different human heavy chain transgenes (HCo7 / HCo12). Alternatively or additionally, the KM Mouse ™ In an exemplary embodiment, the mice will be engineered to selectively produce human IgG2 antibodies. Generation of fusion tumors producing human monoclonal antibodies In certain embodiments, fusion tumors producing human monoclonal anti-VISTA antibodies according to the present invention can be produced using spleen cells and / or lymph node cells from immunized mice can be isolated and fused with appropriate immortalized cell lines (such as mouse myeloma cell lines). The resulting fusion tumors can be screened for the production of antigen-specific antibodies. For example, a single cell suspension of spleen lymphocytes from immunized mice can be fused with one-sixth the number of P3X63-Ag8.653 non-secreting mouse myeloma cells (ATCC, CRL 1580) and 50% PEG. The cells are cultured at approximately 2×10 5Plate cells in flat-bottomed microtiter plates and incubate for two weeks in selective medium containing 20% ​​fetal serum, 18% 653-conditioned medium, 5% origen (IGEN), 4 mM L-glutamine, 1 mM sodium pyruvate, 5 mM HEPES, 0.055 mM 2-mercaptoethanol, 50 units / ml penicillin, 50 mg / ml streptomycin, 50 mg / ml gentamycin, and 1X HAT (Sigma; HAT added 24 hours after fusion). Approximately two weeks later, cells can be cultured in medium in which HAT is replaced with HT. Individual wells can then be screened by ELISA for human monoclonal IgM and IgG antibodies. Once substantial fusion tumor growth has occurred, the culture medium can typically be monitored after 10 to 14 days. Antibody-secreting hybridomas can be replated, screened again, and if still positive for human IgG, the monoclonal antibodies can be subcloned at least twice by limiting dilution. Stable subclones can then be cultured in vitro to produce small amounts of antibody in tissue culture medium for characterization. To purify human monoclonal antibodies, selected hybridomas can be grown in 2-liter spinner flasks for monoclonal antibody purification. The supernatant can be filtered and concentrated before affinity chromatography on protein A-agarose (Pharmacia, Piscataway, NJ). The eluted IgG is checked by gel electrophoresis and high-performance liquid chromatography to ensure purity. The buffer solution can be exchanged into PBS and the concentration can be determined by OD280 using an extinction coefficient of 1.43. The monoclonal antibodies can be aliquoted and stored at -80°C. Generation of transfectomas producing monoclonal antibodies In certain embodiments, for example, a combination of recombinant DNA technology and gene transfection methods, such as those well known in the art, may be used (e.g., Morrison, S. (1985) Science229: 1202), anti-VISTA antibodies according to the present invention are produced in host cell transfectomas. For example, to express antibodies or antibody fragments thereof, DNA encoding partial or full-length light and heavy chains can be obtained by standard molecular biotechnology (e.g., using a fusion tumor expressing an antibody of interest for PCR amplification or cDNA cloning), and the DNA can be inserted into an expression vector so that the gene is operably linked to transcription and translation control sequences. In this context, the term "operably linked" is intended to mean that the antibody gene is joined to a vector so that the transcription and translation control sequences within the vector exert their intended functions of regulating the transcription and translation of the antibody gene. Expression vectors and expression control sequences compatible with the expression host cells used are selected. The antibody light chain gene and the antibody heavy chain gene can be inserted into a separate vector, or more generally, the two genes are inserted into the same expression vector. The antibody gene is inserted into the expression vector by standard methods (e.g., the junction of complementary restriction sites on the antibody gene fragment and the vector, or blunt-end junction if no restriction sites are present). The light and heavy chain variable regions of the antibodies described herein can be used to generate full-length antibody genes of any antibody isotype by inserting them into expression vectors encoding the heavy and light chain constant regions of the desired isotype, such that V H The segment is operably linked to the C H Segment and V L The segment is operably linked to the C L Additionally or alternatively, the recombinant expression vector may encode a signal peptide that promotes secretion of the antibody chain from the host cell. The antibody chain gene may be cloned into the vector so that the signal peptide is linked in-frame to the amino terminus of the antibody chain gene. The signal peptide may be an immunoglobulin signal peptide or a heterologous signal peptide (i.e., a signal peptide from a non-immunoglobulin protein). Characterization of Antibodies Bound to Antigens In certain embodiments, the binding specificity of the agonist anti-VISTA antibodies according to the present invention is determined by known antibody binding analysis techniques (such as ELISA). In an exemplary ELISA, a microtiter plate is coated with purified antigen, here 0.25 μg / ml of VISTA in PBS, and then blocked with 5% bovine serum albumin in PBS. An antibody dilution (e.g., a plasma dilution from an immunized mouse) is added to each well and incubated at 37 ° C for 1 to 2 hours. The culture plate is washed with PBS / Tween and then incubated at 37 ° C for 1 hour with a secondary reagent conjugated to alkaline phosphatase (e.g., goat-anti-human IgG Fc-specific polyclonal reagent for human antibodies). After washing, the culture plate is developed with pNPP substrate (1 mg / ml) and analyzed at an OD of 405 to 650. The mouse that produces the highest titer is preferably used for fusion. ELISA analysis as described above can also be used to screen for fusion tumors that show positive reactivity with the VISTA immunogen. Fusion tumors that bind to VISTA with high affinity are subcloned and further characterized. One clone from each fusion tumor that retains the reactivity of the parental cells (by ELISA) can be selected for the production of 5 to 10 vial cell banks stored at -140°C and for antibody purification. To purify anti-VISTA antibodies, selected hybridomas can be grown in 2-liter spinner flasks for monoclonal antibody purification. The supernatant can be filtered and concentrated, followed by affinity chromatography with protein A-agarose (Pharmacia, Piscataway, NJ). The eluted IgG is checked by gel electrophoresis and high-performance liquid chromatography to ensure purity. The buffer solution can be exchanged into PBS and the concentration can be determined by using an OD280 with an extinction coefficient of 1.43. The monoclonal antibody can be aliquoted and stored at -80°C. To determine whether the selected anti-VISTA monoclonal antibody binds to a unique antigenic determinant, commercially available reagents (Pierce, Rockford, 11.) can be used to biotinylate each antibody. Competition studies using unlabeled monoclonal antibodies and biotinylated monoclonal antibodies can be performed using VISTA-coated ELISA plates as described above. Biotinylated mAb binding can be detected by a streptavidin-alkaline phosphatase probe. To determine the isotype of the purified antibody, an isotype ELISA can be performed using a reagent specific for antibodies of a particular isotype (e.g., IgG2). For example, to determine the isotype of a human monoclonal antibody, the wells of a microtiter plate can be coated overnight with 2 μg / ml of anti-human immunoglobulin at 4°C. After blocking with 1% BSA, the plate is reacted with 1 μg / ml or less of the test monoclonal antibody or purified isotype control at ambient temperature for one to two hours. Each well can then be reacted with a probe conjugated to human IgG1 or human IgM-specific alkaline phosphatase. The plate is developed and analyzed as described above. The reactivity of anti-VISTA human IgG and VISTA antigen can be further tested separately by Western blotting. Briefly, VISTA antigen can be prepared and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. After electrophoresis, the separated antigen is transferred to a nitrocellulose membrane, blocked with 10% fetal bovine serum and probed with the monoclonal antibody to be tested. Human IgG binding can be detected using anti-human IgG alkaline phosphatase and developed with BCIP / NBT substrate tablets (Sigma Chem. Co., St. Louis, Mo.). In another aspect, the present invention features an antibody-drug conjugate (ADC) consisting of an antibody (or antibody fragment, such as a single-chain variable fragment (scFv)) linked to a payload drug (usually a cytotoxic drug). The antibody causes the ADC to bind to the target cancer cell. The ADC is then often internalized by the cell and the drug is released into the cell. Due to the target, side effects are lower and a wider therapeutic window is created. A hydrophilic linker (e.g., PEG4Mal) helps prevent the drug from being drawn out of the cancer-fighting cells via MDR (multidrug resistance) transporters. In another aspect, the present invention features an immunoconjugate comprising an anti-VISTA antibody or fragment thereof conjugated to a therapeutic agent, such as a cytotoxin, a drug (e.g., an immunosuppressant), or a radiotoxin. Such conjugates are referred to herein as "immunoconjugates." Immunoconjugates that include one or more cytotoxins are referred to as "immunotoxins." Cytotoxins or cytotoxic agents include any agent that is detrimental to cells (e.g., kills cells). Examples include Taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin, and analogs or homologs thereof. Therapeutic agents also include, for example, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thiotepa, chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclophosphamide (cyclophosphamide), busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclines such as daunomycin (formerly known as daunomycin) and doxorubicin, antibiotics such as dactinomycin (formerly known as actinomycin), bleomycin, mithramycin, and anthramycin (AMC), and antimitotics such as vincristine and vinblastine. Other examples of therapeutic cytotoxins that can be conjugated to antibodies according to at least some embodiments of the present invention include duocarmycin, calicheamicin, maytansine, and auristatin and their derivatives. An example of a calicheamicin antibody conjugate is commercially available (Mylotarg ™ Wyeth). Cytotoxins can be conjugated to antibodies according to at least some embodiments of the present invention using linker technology available in the art. Examples of linker types that have been used to conjugate cytotoxins to antibodies include, but are not limited to, linkers containing hydrazones, thioethers, esters, disulfides, and peptides. Linkers can be selected, for example, that are readily cleaved by the low pH within the lysosomal compartment or that are readily cleaved by proteases, such as proteases preferentially expressed in tumor tissue, such as cathepsins (e.g., cathepsins B, C, D). See also Saito, G. et al. (2003) for further discussion of cytotoxin types, linkers, and methods for conjugating therapeutic agents to antibodies. Adv. Drug Deliv. Rev. 55: 199-215; Trail, PA et al. (2003) Cancer Immunol. Immunother. 52:328-337; Payne, G. (2003) Cancer Cell3:207-212; Allen, TM (2002) Nat. Rev. Cancer2:750-763; Pastan, I. and Kreitman, RJ (2002) Curr. Opin. Investig. Drugs 3: 1089-1091; Senter, PD and Springer, CJ (2001) Adv. Drug Deliv. Rev. 53:247-264. The antibodies of the present invention may also be conjugated to radioactive isotopes to produce cytotoxic radiopharmaceuticals, also known as radioimmunoconjugates. Examples of radioisotopes that can be conjugated to antibodies for diagnostic or therapeutic purposes include, but are not limited to, iodine-131, indium-111, yttrium-90, and lutetium-177. Methods for preparing radioimmunoconjugates are well established in the art. Radioimmunoconjugates are commercially available, including Zevalin. ® (BiogenlDEC) and Bexxar ® (Corixa Pharmaceuticals) and similar methods can be used to prepare radioimmunoconjugates using antibodies according to at least some embodiments of the present invention. Agonist anti-human VISTA antibodies and conjugates containing the same according to at least some embodiments of the present invention can be used to modify a given biological response, and the drug moiety is not to be construed as limited to classical chemotherapeutic agents. For example, the drug moiety can be a protein or polypeptide having a desired biological activity. Such proteins can include, for example, enzymatically active toxins or active fragments thereof, such as abrin, ricin A, Pseudomonas exotoxin, or diphtheria toxin; proteins such as tumor necrosis factor or interferon-γ; or biological response modifiers such as lymphokines, interleukin-1 ("IL-1"), interleukin-2 ("IL-2"), interleukin-6 ("IL-6"), granulocyte-macrophage colony-stimulating factor ("GM-CSF"), granulocyte-macrophage colony-stimulating factor ("G-CSF"), or other growth factors. Techniques for conjugating therapeutic moieties to antibodies are well known; see, for example, Arnon et al., "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy," in In Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243–56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery,” in In Controlled Drug Delivery (2nd ed.), Robinson et al. (eds.), pp. 623–53 (Marcel Dekker, Inc. 1987); Thorpe, “Carriers of Cytotoxic Agents in Cancer Therapy: A Review,” in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); "Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy", in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985) and Thorpe et al., "The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates", Immunol. Rev., 62: 119-58 (1982). Bispecific molecules According to at least some embodiments, the present invention also encompasses multispecific anti-VISTA agonist antibodies. Multispecific antibodies are monoclonal antibodies that have binding specificity for at least two different sites. In another aspect, the present invention features bispecific molecules comprising anti-VISTA antibodies or fragments thereof according to at least some embodiments of the present invention. The antibody or antigen-binding portion thereof according to at least some embodiments of the present invention can be derivatized or linked to another functional molecule, such as another peptide or protein (e.g., another antibody or ligand for a receptor) to produce a bispecific molecule that binds to at least two different binding sites or target molecules. The antibody according to at least some embodiments of the present invention can actually be derivatized or linked to more than one other functional molecule to produce a multispecific molecule that binds to more than two different binding sites and / or target molecules; the term "bispecific molecule" as used herein is also intended to encompass such multispecific molecules. To produce bispecific molecules according to at least some embodiments of the present invention, the antibody can be functionally linked (e.g., by chemical coupling, genetic fusion, non-covalent association or other means) to one or more other binding molecules, such as another antibody, antibody fragment, peptide or binding mimetic, in order to produce a bispecific molecule. In certain embodiments, one of the binding specificities of a bispecific antibody is for VISTA and the other is for any other antigen. In certain embodiments, a bispecific antibody can bind to two different antigenic determinants of VISTA. Bispecific antibodies can also be used to localize cytotoxic agents to cells expressing VISTA. Bispecific antibodies can be prepared as full-length antibodies or antibody fragments. Bispecific antibodies according to at least some embodiments of the present invention are antibodies that simultaneously bind to two targets having different structures. Bispecific antibodies (bsAbs) and bispecific antibody fragments (bsFabs) according to at least some embodiments of the present invention have at least one arm that specifically binds to a B cell antigen or antigenic determinant and at least one other arm that specifically binds to a targetable binding agent. According to at least some embodiments, the present invention also encompasses fusion antibody proteins, which are recombinantly produced antigen-binding molecules in which two or more different single-chain antibodies or antibody fragment segments with the same or different specificities are connected. Various bispecific fusion antibody proteins can be produced using molecular engineering. In one form, the bispecific fusion antibody protein is monovalent, for example, consisting of a fragment having a single binding site for one antigen and a Fab fragment having a single binding site for a second antigen. In another form, the bispecific fusion antibody protein is divalent, for example, consisting of an IgG having two binding sites for one antigen and two scFvs having two binding sites for a second antigen. The present invention further encompasses engineered antibodies with three or more functional antigen-binding sites, including "octopus antibodies" (see, e.g., US 2006 / 0025576A1) and "dual-acting FAb" or "DAF" antibodies comprising antigen-binding sites that bind to VISTA and another, different antigen (see, e.g., US 2008 / 0069820). Thus, the present invention includes bispecific molecules comprising at least one first binding specificity for VISTA and a second binding specificity for a second target epitope. According to at least some embodiments of the present invention, the second target epitope is an Fc receptor, such as human FcγRI (CD64) or human FcαR receptor (CD89). Thus, the present invention includes bispecific molecules capable of binding to FcγR, FcαR, or FcsR-expressing effector cells (e.g., monocytes, macrophages, or polymorphonuclear cells (PMNs)), respectively, and to target cells expressing VISTA. These bispecific molecules target VISTA-expressing cells to effector cells and trigger Fc receptor-mediated effector cell activities, such as phagocytosis of VISTA-expressing cells, antibody-dependent cell-mediated cytotoxicity (ADCC), cytokine release, or superoxide anion generation. According to at least some embodiments of the present invention, wherein the bispecific molecule is multispecific, the molecule may further include a third binding specificity in addition to the anti-Fc binding specificity. In one embodiment, the third binding specificity is an anti-enhancement factor (EF) portion, such as a molecule that binds to a surface protein involved in cytotoxic activity and thereby increases the immune response against the target cell. An "anti-enhancement factor portion" can be an antibody, functional antibody fragment, or ligand that binds to a given molecule (e.g., an antigen or receptor) and thereby results in an enhancement of the effect of the binding determinant on an Fc receptor or target cell antigen. An "anti-enhancement factor portion" can bind to an Fc receptor or target cell antigen. Alternatively, the anti-enhancement factor portion can bind to an entity that is different from the entity bound by the first and second binding specificities. For example, the anti-enhancement factor portion can bind to a cytotoxic T cell (e.g., via CD2, CD3, CD8, CD28, CD4, CD40, ICAM-1, or other immune cell that results in an increased immune response against the target cell). According to at least some embodiments of the present invention, the bispecific molecule comprises at least one antibody or antibody fragment thereof (including, for example, Fab, Fab', F(ab')2, Fv, or single-chain Fv) as a binding specificity. The antibody may also be a light chain or heavy chain dimer, or any minimal fragment thereof, such as an Fv or single-chain construct, as described in U.S. Patent No. 4,946,778 to Ladner et al., the contents of which are expressly incorporated herein by reference. In one embodiment, binding specificity for an Fcγ receptor is provided by a monoclonal antibody whose binding is not blocked by human immunoglobulin G (IgG). As used herein, the term "IgG receptor" refers to any of the eight gamma-chain genes located on chromosome 1. These genes encode a total of twelve transmembrane or soluble receptor isoforms, grouped into three classes of Fcγ receptors: FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16). In a preferred embodiment, the Fcγ receptor is human high-affinity FcγRI. Human FcγRI is a 72 kDa molecule that exhibits high affinity for monomeric IgG. The generation and characterization of certain preferred anti-Fcγ monoclonal antibodies are described by Fanger et al. in PCT Publication WO 88 / 00052 and U.S. Patent No. 4,954,617, the teachings of which are incorporated herein by reference in their entirety. These antibodies bind to an antigenic determinant of FcγRI, FcγRII or FcγRIII at a site distinct from the Fcγ binding site of the receptor, and therefore their binding is not substantially blocked by physiological levels of IgG. Known anti-FcγRI antibodies include mAb 22, mAb 32, mAb 44, mAb 62, and mAb 197. mAb 32 produced by the hybridoma can be purchased from the American Type Culture Collection, ATCC accession number HB9469. In other embodiments, the anti-Fcγ receptor antibody is a humanized form of monoclonal antibody 22 (H22). The generation and characterization of the H22 antibody are described in Graziano, RF et al. (1995). J. Immunol. 155 (10): 4996-5002 and described in PCT Publication WO 94 / 10332. The cell line producing the H22 antibody is deposited with the American Type Culture Collection under the name HA022CLI and has accession number CRL 11177. In yet other embodiments, binding specificity for an Fc receptor is provided by an antibody that binds to a human IgA receptor, such as the Fc-α receptor (Fc αRI (CD89)), whose binding is preferably not blocked by human immunoglobulin A (IgA). The term "IgA receptor" is intended to include the gene product of an α-gene (Fc α RI) located on chromosome 19. This gene is known to encode several alternatively spliced ​​transmembrane isoforms of 55 to 10 kDa. Fc α RI (CD89) is constitutively expressed on monocytes / macrophages, eosinophils, and neutrophils, but not on non-effector cell populations. Fc α RI has an intermediate affinity for both IgA1 and IgA2 (approximately 5×10 -7 M -1 ), which increases upon exposure to cytokines such as G-CSF or GM-CSF (Morton, HC et al. (1996) Critical Reviews in Immunology 16:423-440). Four FcαRI-specific monoclonal antibodies identified as A3, A59, A62, and A77 have been described that bind to FcαRI outside the IgA ligand binding domain (Monteiro, RC et al. (1992) J. Immunol. 148: 1764). Although human monoclonal antibodies are preferred, other antibodies that can be used in the bispecific molecules according to at least some embodiments of the present invention are murine, chimeric and humanized monoclonal antibodies. Methods known in the art can be used to prepare the bispecific molecules of the present invention by combining constitutive binding specificities (e.g., anti-FcR and anti-VISTA binding specificities). For example, the binding specificity of each bispecific molecule can be generated separately and then combined with each other. When the binding specificity is a protein or peptide, various coupling agents or cross-linking agents can be used for covalent binding. Examples of cross-linking agents include protein A, carbodiimide, N-succinimidyl-S-acetyl-thioacetate (SATA), 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB), o-phenylenedimaleimide (oPDM), N-succinimidyl-3-(2-pyridyl-dithiopropionate) (SPDP), and sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC) (see, e.g., Karpovsky et al. (1984)). J. Exp. Med. 160: 1686; Liu, MA et al. (1985) Proc. Natl. Acad. Sci. USA 82:8648). Other methods include those described by Paulus (1985) Behring Ins. Mitt. No. 78, 118-132; Brennan et al. (1985) Science 229:81-83) and Glennie et al. (1987) J. Immunol. 139: 2367-2375). Preferred binding agents are SATA and sulfo-SMCC, both available from Pierce Chemical Co. (Rockford, IL). When the binding moiety is an antibody, it can be bound via sulfhydryl bonding at the C-terminal hinge regions of the two heavy chains. In a particularly preferred embodiment, the hinge region is modified to contain an odd number of sulfhydryl residues, preferably one, prior to binding. Alternatively, the two binding specificities can be encoded in the same vector and expressed and assembled in the same host cell. This method is particularly suitable when the bispecific molecule is a mAbXmAb, mAbXFab, FabXF(ab')2 or ligandXFab fusion protein. The bispecific molecule according to at least some embodiments of the present invention may be a single-chain molecule comprising a single-chain antibody and a binding determinant or a single-chain bispecific molecule comprising two binding determinants. The bispecific molecule may comprise at least two single-chain molecules. Methods for preparing bispecific molecules are described, for example, in U.S. Patent No. 5,260,203, U.S. Patent No. 5,455,030, U.S. Patent No. 4,881,175, U.S. Patent No. 5,132,405, U.S. Patent No. 5,091,513, U.S. Patent No. 5,476,786, U.S. Patent No. 5,013,653, U.S. Patent No. 5,258,498 and U.S. Patent No. 5,482,858. Techniques for preparing multispecific antibodies include, but are not limited to, recombinant co-expression of two immunoglobulin heavy chain-light chain pairs with different specificity sites (see Milstein and Cuello, Nature 305: 537 (1983)), WO 93 / 08829 and Traunecker et al., EMBO J. 10: 3655 (1991)) and "knob-in-hole" engineering (see, for example, U.S. Patent No. 5,731,168). Multispecific antibodies can also be prepared by engineering electrostatic steering to produce antibody Fc-heterodimer molecules (WO 2009 / 089004A1); controlled Fab-arm exchange (see Labrijn et al., Proc. Natl. Acad. Sci. USA 110(13):5145-50 (2013)); cross-linking two or more antibodies or fragments (see, for example, U.S. Pat. No. 4,676,980 and Brennan et al., Science, 229: 81 (1985)); the use of leucine zippers to generate bispecific antibodies (see, e.g., Kostelny et al., J. Immunol., 148(5): 1547-1553 (1992)); the use of "diabody" technology for the preparation of bispecific antibody fragments (see, e.g., Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993); and using single-chain Fv (sFv) dimers (see, e.g., Gruber et al., J. Immunol., 152:5368 (1994)); and as, for example, Tutt et al. The trispecific antibodies were prepared as described in J. Immunol. 147: 60 (1991). For example, the binding of a bispecific molecule to its specific target can be confirmed by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), FACS analysis, bioassay (e.g., growth inhibition), or Western blot analysis. Each of these assays typically detects the presence of a protein-antibody complex of particular interest by employing a labeled reagent (e.g., an antibody) that is specific for the complex of interest. For example, an FcR-antibody complex can be detected using, for example, an enzyme-linked antibody or antibody fragment that recognizes and specifically binds to the antibody-FcR complex. Alternatively, the complex can be detected using any of a variety of other immunoassays. For example, an antibody can be radiolabeled and used in a radioimmunoassay (RIA) (see, e.g., Weintraub, B., et al., 2002). Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated herein by reference.) Radioisotopes can be detected, for example, using a gamma counter or scintillation counter or by autoradiography. Uses of antagonist antibodies and pharmaceutical compositions containing the same for cancer immunotherapy Unlike targeted tumor therapies, which aim to inhibit molecular pathways important for tumor growth and progression and / or deplete tumor cells, cancer immunotherapy aims to stimulate the patient's own immune system to eliminate cancer cells, providing long-term tumor destruction. Various approaches can be used in cancer immunotherapy, particularly therapeutic cancer vaccines to induce tumor-specific T cell responses and immunostimulatory antibodies (i.e., antagonists of inhibitory receptors = immune checkpoints) to remove immune inhibitory pathways. Clinical responses to targeted therapies, or conventional anticancer therapies, tend to be temporary as cancer cells develop resistance and tumors relapse. However, the clinical use of cancer immunotherapy over the past few years has demonstrated that this type of therapy can produce durable clinical responses, demonstrating a dramatic impact on long-term survival. However, despite these long-term responses, only a small number of patients respond (in contrast to conventional or targeted therapies, where a large number of patients respond, but responses are temporary). By the time tumors are clinically detected, they have already evaded the immune defense system by acquiring immune tolerance and immunosuppressive properties, creating an immunosuppressive tumor microenvironment through various mechanisms and immune cell types. Therefore, in cancer immunotherapy, it is becoming increasingly clear that combination therapies are necessary for clinical efficacy. A combination approach is needed and is expected to increase the number of patients who benefit from immunotherapy and expand the number and type of responsive cancers, expanding the potential cancer indications of checkpoint agents to more than the initial indications currently showing the efficacy of immune checkpoint blockade as a single therapy. The combination of immunomodulatory methods is intended to maximize the results and overcome the tolerance mechanisms of most tumors to single methods. Therefore, tumors that are traditionally considered non-immunogenic may become immunogenic and respond to immunotherapy, despite the co-administration of pro-immunogenic therapies designed to increase the patient's anti-tumor immune response. Possible triggers are described in detail below. The scientific rationale underlying the dramatic increase in efficacy of combination therapies posits that immune checkpoint blockade as a monotherapy will induce tumor regression only when a robust anti-tumor immune response pre-exists that is "unleashed" at the time of pathway blockade. According to at least some embodiments of the present invention, VISTA-specific antibodies, antibody fragments, conjugates, and compositions comprising the same are used to treat all types of cancer via cancer immunotherapy in combination therapies. As used herein, the term "treat" refers to both therapeutic treatment and prophylactic or preventative measures, in this case, regarding the treatment of inflammatory side effects of cancer. However, as described below, the use of antibodies and pharmaceutical compositions for the treatment of infectious diseases, sepsis, and / or autoimmune conditions and / or for suppressing undesirable immune activation following gene therapy is also provided. Those in need of treatment include those already suffering from cancer as well as those in whom cancer is to be prevented. Thus, mammals to be treated herein may have been diagnosed with cancer or may be predisposed to or susceptible to cancer. As used herein, the term "treat" refers to preventing, delaying the onset, curing, reversing, attenuating, alleviating, minimizing, suppressing, halting, or stabilizing the adverse effects of the aforementioned cancerous disease, disorder, or condition. Management of cancer, as described above, is also encompassed. "Management" means reducing the severity of the disease, reducing the frequency of disease attacks, reducing the duration of such attacks, reducing the severity of such attacks, slowing / reducing cancer cell growth or proliferation, slowing the progression of at least one symptom, improving at least one measurable physical parameter, and the like. For example, immunostimulatory anti-VISTA antibodies should promote T cell or NK or cytokine immunity against target cells (e.g., cancer cells, infected cells, or pathogen cells), and thereby treat cancer or infectious diseases by depleting cells involved in the disease condition. Potent anti-VISTA antibodies should reduce T cell or NK activity and / or secretion of proinflammatory cytokines involved in the disease pathology of certain immune diseases (such as autoimmune, inflammatory, or allergic conditions), and thereby treat or alleviate the disease pathology and tissue destruction associated with such conditions (e.g., joint destruction associated with rheumatoid arthritis conditions). For therapeutic purposes, "mammal" refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals such as dogs, horses, cats, cows, etc. The mammal is preferably a human. The mammal is preferably a human diagnosed with one of the diseases, disorders, or conditions described above, or a human predisposed to at least one cancer. A "therapeutically effective amount" refers to an amount of an agent according to the present invention that is effective in treating a disease or condition in a mammal. The therapeutic agents of the present invention can be provided to a subject alone or as part of a pharmaceutical composition in which they are mixed with a pharmaceutically acceptable carrier. According to at least some embodiments of the present invention, the anti-VISTA antibodies, fragments, conjugates thereof, and / or pharmaceutical compositions comprising the same as described herein may also be administered in combination therapy, i.e., in combination with other potentiating agents and / or other treatments. According to at least some embodiments, the anti-VISTA antibodies may be used in combination with any of the standard cancer treatment regimens known in the art (e.g., as found at http: / / www.cancer.gov / cancertopics). For example, combination therapies may include an anti-VISTA antibody, fragment, conjugate thereof, and / or pharmaceutical composition comprising the same, in combination with at least one other therapeutic agent or immunomodulatory agent, other compound, or immunotherapy or immunostimulatory strategy as described herein. Antagonistic anti-VISTA antibodies can be used in combination with agonistic antibodies targeting immune checkpoints, including anti-CTLA4 mAbs, such as ipilimumab and tremelimumab; anti-PD-1, such as nivolumab, BMS-936558 / MDX-1106 / ONO-4538, AMP224, CT-011, and MK-3475; anti-PDL-1 antagonists, such as BMS-936559 / MDX-1105, MEDI4736, and RG-7446 / MPDL3280A; anti-LAG-3, such as IMP-321, anti-TIM-3, anti-BTLA, anti-B7-H4, and anti-B7-H3; and agonistic antibodies targeting immunostimulatory proteins, including anti-CD40. mAbs such as CP-870, 893, lucatumumab, dacetuzumab; anti-CD137 mAbs such as BMS-663513, urelumab, PF-05082566; anti-OX40 mAbs such as anti-OX40; anti-GITR mAbs such as TRX518; anti-CD27 mAbs such as CDX-1127; and anti-ICOS mAbs. Cytokines are molecular messengers that allow cells of the immune system to communicate with each other to produce a coordinated, strong, but self-limiting response to a target antigen. Cytokine-based therapies specifically attempt to directly stimulate the patient's own immune system to reject cancer. The past two decades have seen a growing interest in harnessing the immune system to eradicate cancer, accompanied by intense efforts to characterize cytokines and exploit their vast signal transduction networks to develop cancer treatments. Cytokines directly stimulate immune effector cells and stromal cells at the tumor site and enhance the recognition of tumor cells by cytotoxic effector cells. Numerous studies in animal tumor models have demonstrated that cytokines have broad anti-tumor activity and this has translated into a variety of cytokine-based approaches for cancer treatment (Lee and Margolin 2011, Cancers 3(4):3856-93). Many cytokines are in preclinical or clinical development as potential anti-tumor immune response agents for cancer immunotherapy, including, in particular, IL-2, IL-7, IL-12, IL-15, IL-17, IL-18, IL-21, IL-23, IL-27, GM-CSF, IFNα (interferon α), IFNβ, and IFNγ. Antagonist anti-VISTA antibodies and pharmaceutical compositions containing the same can also be administered in combination with other compounds or immunotherapies. For example, combination therapies may include a compound of the invention in combination with at least one other therapeutic agent or immunomodulatory agent or immunostimulatory strategy, including but not limited to, tumor vaccines, receptive T cell therapy, Treg depletion, antibodies (e.g., bevacizumab, Erbitux), peptides, peptibodies, small molecules, chemotherapeutic agents (such as cytotoxic and cell proliferation inhibitors, e.g., paclitaxel, cisplatin, vinorelbine, docetaxel, gemcitabine, temozolomide, irinotecan, 5FU, carboplatin), immune modifiers (such as interferons and interleukins), immunostimulatory antibodies, growth hormone or other cytokines, folic acid, vitamins, minerals, aromatase inhibitors, RNAi, histone deacetylase inhibitors, proteasome inhibitors, and the like. According to at least some embodiments, immune cells (preferably T cells) can be contacted with the therapeutic agent of the present invention in vivo or in vitro to modulate the immune response. The T cells contacted with the therapeutic agent may be any cells expressing T cell receptors (including α / β and γ / δ T cell receptors). T cells include all cells expressing CD3, including T cell subsets that also express CD4 and CD4. T cells include untreated and memory cells and effector cells, such as CTL. T cells also include cells such as Th1, Tel, Th2, Th2, Th3, Th17, Th22, Treg and Tr1 cells. T cells also include NKT cells and similar unique categories of T cell lineages. Use of agonistic anti-VISTA antibodies and pharmaceutical compositions containing the same for the treatment of autoimmune diseases According to at least some embodiments, anti-VISTA antibodies, fragments, conjugates thereof, or pharmaceutical compositions comprising the same that act as VISTA stimulatory therapeutics as described herein can be used to treat immune system-related diseases. Immune system related conditions optionally include immune related conditions, autoimmune diseases such as those cited herein, transplant rejection and graft-versus-host disease and / or for blocking or promoting VISTA-mediated immune stimulation, immune related diseases such as those cited herein and / or for immunotherapy (promoting or suppressing immune stimulation). The immune condition is optionally selected from an autoimmune disease, transplant rejection, an inflammatory disease, an allergic condition, or graft-versus-host disease. The treatment is optionally combined with another moiety suitable for treating an immune-related condition. Thus, treatment of multiple sclerosis using agents according to at least some embodiments of the present invention can be combined, for example, with any known therapeutic agent or method for treating multiple sclerosis, as optionally described herein. Thus, treatment of rheumatoid arthritis or other arthritic conditions using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating rheumatoid arthritis, as optionally described herein. Thus, treatment of IBD using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating IBD, as optionally described herein. Thus, treatment of psoriasis using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating psoriasis, as optionally described herein. Thus, treatment of type 1 diabetes using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating type 1 diabetes, as optionally described herein. Thus, treatment of uveitis using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating uveitis, as optionally described herein. Thus, treatment of psoriasis using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating psoriasis, as optionally described herein. Thus, treatment of Sjögren's syndrome using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating Sjögren's syndrome, as optionally described herein. Thus, treatment of systemic lupus erythematosus using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating systemic lupus erythematosus, as optionally described herein. Thus, treatment of GVHD using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating GVHD, as optionally described herein. Thus, treatment of chronic or acute infection and / or hepatotoxicity associated therewith (e.g., hepatitis) using the agonist antibodies of the invention can be combined, for example, with any known therapeutic agent or method for treating chronic or acute infection and / or hepatotoxicity associated therewith, as optionally described herein. In the above treatments, a subject suffering from one of the above or other autoimmune or inflammatory conditions is preferably administered an immunosuppressive anti-VISTA antibody disclosed herein or an antigen-binding fragment according to the present invention, which mimics or stimulates at least one VISTA-mediated effect on immunity, such as inhibition of cytotoxic T cell or NK activity and / or production of proinflammatory cytokines involved in disease pathology, thereby preventing or ameliorating disease symptoms and potentially leading to long-term remission, for example due to induction of Tregs that induce T cell tolerance or prolonged immunosuppression. According to at least some embodiments of the present invention, the therapeutic agents and / or pharmaceutical compositions comprising the same as recited herein can be administered as the sole active ingredient or in combination with other drugs or other anti-inflammatory agents in an immunomodulatory regimen, for example, to treat or prevent acute or chronic rejection of allogeneic or xenografts or inflammatory or autoimmune disorders or to induce tolerance. Use of agonistic anti-VISTA antibodies and pharmaceutical compositions containing the same for the treatment of sepsis According to at least some embodiments, the VISTA antibodies, fragments, conjugates thereof and / or pharmaceutical compositions described herein can be used to treat sepsis. Sepsis is a potentially life-threatening complication of infection. Sepsis represents a complex clinical syndrome that occurs when the initial host response to infection is inappropriately amplified and dysregulated, resulting in a host-harmful condition. The initial hyperinflammatory phase ("cytokine storm") in sepsis is followed by an immunosuppressive state (Hotchkiss et al. 2013). Lancet Infect. Dis. 13:260-268). This late stage of impaired immunity (also known as "immune paralysis") is characterized by an inability to identify the initial infection, reactivated viruses (such as HSV and cytomegalovirus), and the development of new secondary infections, whose organisms are often not particularly virulent to immunocompetent patients. Most sepsis patients now survive the initial hyperinflammatory episode, only to die in the intensive care unit in the days or weeks following sepsis-induced multi-organ dysfunction. Sepsis-induced immunosuppression is increasingly recognized as the primary immune dysfunction in these vulnerable patients. Impaired pathogen clearance after primary infection and / or susceptibility to secondary infections contribute to the high morbidity and mortality associated with sepsis. According to at least some embodiments of the present invention, there is provided use of the therapeutic agents and / or pharmaceutical compositions comprising the same as recited herein in combination with known therapeutic agents for the effective treatment of sepsis. According to at least some embodiments of the present invention, combinations of therapeutic agents and / or pharmaceutical compositions comprising the same as recited herein are provided in combination with standard of care or novel treatments for sepsis, with treatments that block the cytokine storm during the initial hyperinflammatory phase of sepsis, and / or with therapies with immunostimulatory effects to overcome the immunosuppressive phase induced by sepsis. Standard of care treatment combinations for sepsis, such as the International Guidelines for Management of Severe Sepsis and Septic Shock (Dellinger et al. 2013 Intensive Care Med 39: 165-228), some of which are described below. 1. Broad-spectrum antibiotics active against all possible pathogens (bacteria and / or fungi - treatment is started when sepsis is diagnosed but no specific pathogen has been identified) - an example is cefotaxime (Claforan ® ), Ticarcillin and clavulanate (Timentin ® ), piperacillin and tazobactam (Zosyn ® ), Imipenem and cilastatin (Primaxin ® ), Meropenem (Meropenem ® ), Clindamycin (Cleocin), Metronidazole (Flagyl ® ), Ceftriaxone (Rocephin ® ), Ciprofloxacin (Cipro ® ), Cefepime (Maxipime ® ), Levofloxacin (Levaquin ®), vancomycin or any combination of the listed drugs. 2. Vasopressors: Examples are norepinephrine, dopamine, epinephrine, vasopressin 3. Steroids: Examples: hydrocortisone, dexamethasone or fludrocortisone, intravenous or other treatments that affect muscle contractility: an example is dobutamine for septic patients with myocardial dysfunction 4. Recombinant human activated protein C (rhAPC), such as drotrecogin α (activated) (DrotAA). 5. Beta-blockers that additionally reduce local and systemic inflammation. 6. Metabolic interventions, such as pyruvate, succinate or high-dose insulin substitution. Use of anti-VISTA antibodies and pharmaceutical compositions containing the same for reducing adverse immune activation after gene or cell therapy or transplantation As used herein, the term "gene therapy" encompasses any type of gene therapy, vector-mediated gene therapy, gene transfer, viral-mediated gene transfer and further encompasses certain cell therapies, such as CAR T and CAR NK cell therapies. According to at least some embodiments of the present invention, VISTA antibodies, fragments, conjugates thereof and / or pharmaceutical compositions that target VISTA and have inhibitory activity on immune responses as described herein can be used as therapeutic agents for reducing adverse immune activation after gene or cell therapy for the treatment of various genetic diseases. Without wishing to be limited by a single hypothesis, these antibodies have VISTA-like inhibitory activity on immune responses and / or optionally enhance VISTA immunosuppressive activity by suppressing pathogen T cells and / or NK cells. A variety of gene therapy products for the treatment of genetic diseases are currently in clinical trials. Recent studies have documented the successful treatment of several genetic diseases using gene therapy vectors. Gene therapy strategies are characterized by three important factors: the gene to be transferred, the target tissue into which the gene will be introduced, and the vector (gene delivery vehicle) used to facilitate the entry of the gene into the target tissue. Most gene therapy clinical trials have used viral vectors as very effective delivery vehicles, including retroviruses, benzylviruses, adenoviruses, adeno-associated viruses, pseudotyped viruses, and herpes simplex viruses. However, the interaction between the human immune system and all components of the gene therapy vector appears to represent one of the major limitations to long-term therapeutic efficacy. Human studies have demonstrated a high likelihood of host immune responses to viral vectors. Such immune responses to the virus or transgenic product itself, leading to the formation of neutralizing antibodies and / or destruction of transduced cells by cytotoxic cells, can greatly interfere with the efficacy of treatment (Seregin and Amalfitano 2010). Viruses2:2013; Mingozzi and High 2013 Blood 122:23; Masat et al. 2013 Discov Med. 15:379). Therefore, developing strategies to circumvent immune responses and promote long-term expression of transgenic therapeutic proteins is one of the major challenges for the success of gene therapy in the clinic. Factors that influence the immune response to transgenic proteins encoded by viral vectors include route of administration, vector dose, immunogenicity of the transgenic protein, host inflammatory state, and capsid serotype. These factors are thought to influence immunogenicity by triggering innate immunity, cytokine production, APC maturation, antigen presentation, and ultimately priming of functional effector naive T lymphocytes (Mingozzi and High 2013). Blood 122:23). Therefore, the concept of inhibiting immune activation by interfering with these mechanisms has emerged in order to induce short-term immunosuppression, avoid the induction of early immunity after administration of the vector, and promote long-term tolerance. As a strategy to suppress adverse immune activation after gene therapy, especially after multiple injections, immunomodulatory therapies that target two non-redundant checkpoints of the immune response during vector delivery are tested in animal models. Studies of vector-mediated immune responses on adenoviral vectors instilled into the lungs of mice or monkeys confirmed that brief treatment with anti-CD40L antibodies resulted in suppression of adenovirus-induced immune responses; therefore, the animals should be re-administered with adenoviral vectors. Short-term treatment with Abs thus resulted in long-term effects on immune function and prolonged the suppression of adenovirus-specific humoral responses beyond the time when the Ab effect was no longer significant, indicating the therapeutic potential of blocking this co-stimulatory pathway as an immunomodulatory approach for administering gene transfer vectors (Scaria et al. 1997 Gene Ther. 4: 611; Chirmule et al. 2000 J. Virol. 74: 3345). Other studies have demonstrated that co-administration of CTLA4-Ig and anti-CD40L Ab with the primary vector reduces the immune response to the vector, prolongs long-term adenovirus-mediated gene expression, and allows secondary adenovirus-mediated gene transfer even after the immunosuppressive effects of these agents are no longer present, suggesting that it may be possible to achieve persistence and secondary adenovirus-mediated gene transfer with transient immunosuppressive therapy (Kay et al. 1997). Proc. Natl. Acad. Sci. USA 94:4686). In another study, similar administration of CTLA4-Ig and anti-CD40L Ab abolished the formation of neutralizing Abs against the vector and allowed gene transfer to occur, with the limitation that treatment was administered during each gene transfer injection (Lorain et al. 2008 Molecular Therapy 16:541). In addition, administration of CTLA4-Ig to mice (even a single dose) resulted in suppression of the immune response at early time points and prolonged transgene expression (Adriouch et al. 2011 Front. Microbiol. 2: 199). However, CTLA4-Ig alone is insufficient to permanently eliminate immune responses to transgene products. Combination therapy targeting two immune checkpoints with CTLA4-Ig and PD-L1 or PDL-2 resulted in synergistic improvements in transgene tolerance at later time points, potentially targeting two non-redundant mechanisms of immune regulation, leading to long-term transgene persistence and expression (Adriouch et al. 2011). Front. Microbiol. 2: 199). According to at least some embodiments of the present invention, the agonists of the present invention can be used to overcome the limitations of immune responses on gene therapy and can be used to reduce adverse immune activation after gene therapy alone or with other active substances. Current methods include excluding patients with antibodies to the delivery vector, administering high doses of vector, using empty capsids to absorb anti-vector antibodies to allow subsequent vector transduction, and repeated plasma exchange (plasmapheresis) cycles to absorb immunoglobulins and reduce anti-vector antibody titers. Novel approaches attempting to overcome these limitations can be divided into two main categories: selective modification of the Ad vector itself and pre-immune conditioning of the host (Seregin and Amalfitano 2010). Viruses 2:2013). The first category encompasses several innovative strategies, including: (1) Ad-capsid presentation of specific inhibitors or ligands; (2) covalent modification of the complete Ad vector capsid; (3) use of tissue-specific promoters and localized administration routes; (4) use of genome-modified Ad; and (5) development of chimeric or alternative serotype Ad. The second approach involves the use of immunosuppressive drugs or specific compounds to block important immune pathways known to be induced by viral vectors. Immunosuppressive agents have been tested in preclinical studies and shown to be effective in preventing or eradicating immune responses to the transfer vector and transgene product. These agents include general immunosuppressants such as cyclosporine A; cyclophosphamide; FK506; glucocorticoids or steroids such as dexamethasone; TLR9 blockers such as the TLR9 antagonist oligonucleotide ODN-2088; TNF-α blockers with anti-TNF-α antibodies or TNFR-Ig antibodies, Erk and other signal transduction inhibitors such as U0126. In a clinical setting, the administration of glucocorticoids has been successfully used to blunt T cell responses to viral capsids by hepatic gene transfer of adenovirus-associated virus (AAV) vectors expressing a human factor IX transgene to patients with severe hemophilia B (Nathwani et al. 2011). N. Engl. J. Med. 365:2357). In contrast to previous approaches that used drugs that tended to be "global" and non-specific in their ability to immunosuppress the host, more selective immunosuppressive approaches have been developed. These include the use of agents that block positive co-stimulatory interactions such as those between CD40 and CD154, ICOS and ICOSL, CD28 and CD80 or CD86 (including CTLA4-Ig), NKG2D and its ligands, LFA-1 and ICAM, LFA-3 and CD2, 4-1BB and 4-1BBL, OX40 and OX40L, and GITR and GITRL, as well as agents that stimulate negative co-stimulatory receptors such as CTLA-4, PD-1, BTLA, LAG-3, TIM-1, TEVI-3, KIRs, and receptors for B7-H4 and B7-H3. Some of these agents have been used in preclinical or clinical transplant studies (Pilat et al. 2011). Sem. Immunol. 23:293). In the above-mentioned gene or cell therapy or in the treatment of transplant indications, it is preferred to administer the immunosuppressive anti-VISTA antibodies disclosed herein or the antigen-binding fragments according to the present invention to a subject who has received or is to receive cell or gene therapy or to a transplanted tissue or organ. The antibody enhances, stimulates or simulates at least one VISTA-mediated effect on immunity, such as its inhibitory effect on cytotoxic T cells or NK activity and / or its inhibitory effect on the production of proinflammatory cytokines, or its stimulatory effect on Treg, thereby preventing or reducing the host immune response to the cells or genes used in the therapy or an adverse immune response to transplanted cells, organs or tissues. Treatment will preferably induce prolonged immune tolerance to transplanted or perfused cells, tissues or organs. In certain cases, such as in the case of transplanted cells, tissues or organs containing immune cells, the immunosuppressive anti-VISTA antibodies or antigen-binding fragments disclosed herein may be contacted with cells, tissues or organs before infusion or transplantation, and / or may be contacted with the immune cells of the transplant recipient to tolerate the immune cells and possibly prevent adverse immune reactions or GVHD immune reactions. Pharmaceutical compositions In another aspect, the present invention provides a composition, such as a pharmaceutical composition, containing one or a combination of anti-human VISTA antibodies according to the present invention and, optionally, another immunosuppressant or other active agent. Thus, the present invention is characterized in that a pharmaceutical composition comprising a therapeutically effective amount of an anti-human VISTA antibody according to at least some embodiments of the present invention. In particular, the present invention is characterized in that a pharmaceutical composition comprising a therapeutically effective [immunosuppressive] amount of at least one agonist anti-human VISTA antibody or antibody fragment according to the present invention. The pharmaceutical compositions according to at least some embodiments of the present invention [i.e., in the case of the VISTA antagonist antibodies disclosed herein] can be used to treat cancer, where the cancer is non-metastatic, invasive or metastatic and / or for the treatment of immune-related disorders, autoimmunity, allergy, GVHD, inflammation or hepatotoxicity associated with infectious disorders and / or sepsis [i.e., in the case of the VISTA agonist antibodies disclosed herein]. "Treatment" refers to therapeutic treatment and preventive or prophylactic measures. Those in need of treatment include those who already have the disease and those for whom the disease is to be prevented. Thus, the mammal to be treated herein may have been diagnosed with the disease or may be predisposed to the disease or susceptible to the disease. "Mammal" for therapeutic purposes refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports or pet animals, such as dogs, horses, cats, cows, etc. The mammal is preferably a human. The term "therapeutically effective amount" refers to an amount of an agent according to the present invention that is effective for treating a disease or condition in a mammal. The therapeutic agents of the present invention can be provided to a subject alone or as part of a pharmaceutical composition in which they are mixed with a pharmaceutically acceptable carrier. In many cases, agonist or antagonist anti-VISTA antibodies according to the present invention will be used in combination with other immunotherapeutics or other therapeutic agents suitable for treating a particular condition. A composition is considered to be a "pharmaceutically acceptable carrier" if its administration is tolerated by the recipient patient. As used herein, "pharmaceutically acceptable carriers" include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Preferably, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal, or epidermal administration (e.g., by injection or infusion). Such compositions include sterile water, buffered saline (e.g., Tris-HCl, acetate, phosphate), pH and ionic strength, and optionally additives such as detergents and solubilizers (e.g., polysorbate 20, polysorbate 80), antioxidants (e.g., ascorbic acid, sodium metabisulfite), preservatives (e.g., thimerosal, benzyl alcohol), and bulking substances (e.g., lactose, mannitol). Non-aqueous solvents or vehicles may also be used, as described in detail below. Examples of suitable aqueous and non-aqueous carriers that can be used in pharmaceutical compositions according to at least some embodiments of the present invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like) and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters (such as ethyl oleate). For example, appropriate fluidity can be maintained by using a coating material (such as lecithin), by maintaining the desired particle size in the case of a dispersion, and by using a surfactant. Depending on the route of administration, the active compound that specifically binds to either the VISTA protein or the bispecific molecule (i.e., a single or multiple antibodies and antigen-binding fragments and conjugates containing the same and / or different natural skeletons) can be coated in a material to protect the compound from the effects of acids and other natural conditions that can inactivate the compound. The pharmaceutical compound according to at least some embodiments of the present invention may include one or more pharmaceutically acceptable salts. "Pharmaceutically acceptable salts" are salts that retain the desired biological activity of the parent compound and do not impart any adverse toxicological effects (see, e.g., Berge, SM et al. (1977) J. Pharm. Sci. 66: 1-19). Examples of such salts include acid addition salts and base addition salts. Acid addition salts include those derived from non-toxic inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphorous acid, and the like, and those derived from non-toxic organic acids such as aliphatic monocarboxylic acids and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and the like. Base addition salts include those derived from alkaline earth metals such as sodium, potassium, magnesium, calcium, and the like, and those derived from non-toxic organic amines such as N,N'-dibenzylethylenediamine, N-methylglucamine, chloroprocaine, choline, diethanolamine, ethylenediamine, procaine, and the like. Pharmaceutical compositions according to at least some embodiments of the present invention may also include a pharmaceutically acceptable antioxidant. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, and the like; (2) oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, and the like; and (3) metal chelators such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Such compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers, and dispersants. Prevention of the presence of microorganisms can be ensured by the sterilization procedures described above or by the inclusion of various antibacterial and antifungal agents (e.g., parabens, chlorobutanol, phenol, sorbic acid, and the like). It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like in the composition. Furthermore, prolonged adsorption of injectable pharmaceutical forms can be achieved by the inclusion of agents that delay adsorption (e.g., aluminum monostearate and gelatin). Pharmaceutically acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. The use of such media and agents for pharmaceutically active substances is known in the art. Unless any conventional media or agents are incompatible with the active compound, their use in pharmaceutical compositions according to at least some embodiments of the present invention is contemplated. Supplementary active compounds may also be incorporated into the compositions. Therapeutic compositions generally must be sterile and stable under the conditions of manufacture and storage. Compositions can be formulated as solutions, microemulsions, liposomes, or other ordered structures suitable for high drug concentrations. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, a polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol and the like), and suitable mixtures thereof. Suitable fluidity can be maintained, for example, by the use of a coating (such as lecithin), by maintaining the desired particle size in the case of a dispersion, or by the use of a surfactant. In many cases, it is preferred to include an isotonic agent, such as a sugar, a polyol such as mannitol, sorbitol, or sodium chloride, in the composition. Prolonged adsorption of injectable compositions can be achieved by including an agent that delays adsorption (e.g., monostearate and gelatin) in the composition. Sterile injectable solutions can be prepared by incorporating the desired amount of the active compound in an appropriate solvent with one or a combination of the above-mentioned ingredients, as needed, followed by sterile microfiltration. Dispersions are generally prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the required other ingredients from those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying (lyophilization), which yield a powder of the active ingredient plus any other desired ingredients from a previously sterile-filtered solution thereof. Sterile injectable solutions can be prepared by incorporating the desired amount of the active compound in an appropriate solvent with one or a combination of the above-mentioned ingredients, followed by sterile microfiltration. Dispersions are typically prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the desired other ingredients from those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are vacuum drying and freeze drying (lyophilization), which produce a powder of the active ingredient plus any other desired ingredients from its previously sterile filtered solution. The compositions of the present invention can be administered using one or more of the various methods known in the art via one or more routes of administration. As will be appreciated by those skilled in the art, route of administration and / or mode will vary depending on the desired result. For the therapeutic agent according to at least some embodiments of the present invention, preferred routes of administration include intravenous delivery (e.g., injection or infusion), intravenous, intramuscular, intradermal, intraperitoneal, subcutaneous, spinal, oral, enteral, rectal, pulmonary (e.g., inhalation), nasal, local (including transdermal, buccal, and sublingual), intravesical, intravitreal, intraperitoneal, vaginal, brain delivery (e.g., intraventricular, intracerebral, and convection-enhanced diffusion), CNS delivery (e.g., intrathecal, perimedullar, and spinal) or parenteral (including subcutaneous, intramuscular, intravenous, and intradermal), transmucosal (e.g., sublingual administration), administration or via implantation or other parenteral administration routes, such as by injection or infusion or other delivery routes and / or known administration forms in the art. As used herein, the phrase "parenteral administration" means modes of administration other than enteral and topical administration, usually by injection and includes, but is not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, epidural, and intrasternal injection and infusion. In a specific embodiment, a protein, therapeutic agent, or pharmaceutical composition according to at least some embodiments of the present invention may be administered intraperitoneally or intravenously. Alternatively, the VISTA-specific antibodies according to the present invention can be administered via a non-parenteral route, such as a topical, epidermal or mucosal administration route, for example, intranasally, orally, vaginally, rectally, sublingually or topically. The active compound can be prepared with a carrier that protects the compound from rapid release, such as a controlled release formulation, including implants, transdermal patches, and microencapsulated delivery systems. Biodegradable, biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid can be used. Various methods for preparing such formulations are patented or generally known to those skilled in the art. See, for example, Sustained and Controlled Release Drug Delivery Systems, edited by JR Robinson, Marcel Dekker, Inc., New York, 1978. The therapeutic composition can be administered by medical devices known in the art. For example, in a preferred embodiment, the therapeutic composition according to at least some embodiments of the present invention can be administered by a hypodermic needle injection device, such as the devices disclosed in U.S. Patent Nos. 5,399,163, 5,383,851, 5,312,335, 5,064,413, 4,941,880, 4,790,824, or 4,596,556. Examples of well-known implants and modules suitable for use in the present invention include: U.S. Patent No. 4,487,603, which discloses an implantable microinfusion pump for dispensing drugs at a controlled rate; U.S. Patent No. 4,486,194, which discloses a therapeutic device for transdermal drug administration; U.S. Patent No. 4,447,233, which discloses a drug infusion pump for delivering drugs at a precise infusion rate; U.S. Patent No. 4,447,224, which discloses a variable flow implantable infusion device for continuous drug delivery; U.S. Patent No. 4,439,196, which discloses an osmotic drug delivery system with multiple chamber compartments; and U.S. Patent No. 4,475,196, which discloses an osmotic drug delivery system. These patents are incorporated herein by reference. Many other such implants, delivery systems, and modules are known to those skilled in the art. In certain embodiments, anti-VISTA antibodies can be formulated to ensure proper distribution in vivo. For example, the blood-brain barrier (BBB) ​​excludes a variety of highly hydrophilic compounds. To ensure that the therapeutic compound according to at least some embodiments of the present invention crosses the BBB (if necessary), it can be formulated in liposomes, for example. For methods of making liposomes, see, for example, U.S. Patents 4,522,811, 5,374,548, and 5,399,331. Liposomes may include one or more moieties that are selectively delivered to specific cells or organs, thereby enhancing targeted drug delivery (see, for example, VV Ranade (1989)). J. Clin. Pharmacol. 29:685). Exemplary targeting moieties include folate or biotin (see, e.g., U.S. Pat. No. 5,416,016 to Low et al.); mannose (Umezawa et al., (1988) Biochem. Biophys. Res. Commun. 153: 1038); antibodies (PG Bloeman et al. (1995) FEBS Lett. 357: 140; M. Owais et al. (1995) Antimicrob. Agents Chemother. 39: 180); surfactant protein A receptor (Briscoe et al. (1995) Am. J Physiol. 1233: 134); pl20 (Schreier et al. (1994) J. Biol. Chem. 269:9090); see also K. Keinanen; ML Laukkanen (1994) FEBS Lett. 346: 123; JJ Killion; and IJ Fidler (1994) Immunomethods4:273. In another embodiment, the immunoconjugates of the present invention can be used to target compounds (e.g., therapeutic agents, labels, cytotoxins, radiotoxins, immunosuppressants, etc.) to cells with VISTA cell surface receptors by linking them to antibodies disclosed herein. Therefore, the present invention also provides methods for locating cells expressing VISTA in vitro or in vivo (e.g., by detectable labels, such as radioisotopes, fluorescent compounds, enzymes, or enzyme cofactors). Alternatively, the immunoconjugates can be used to kill cells with VISTA cell surface receptors by targeting cytotoxins or radiotoxins to VISTA antigens. As used herein, "pharmaceutically acceptable carriers" include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents and adsorption delaying agents and the like that are physiologically compatible. The carrier is preferably suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). Depending on the route of administration, the active compound (i.e., a soluble polypeptide conjugate containing the extracellular domain of the VISTA antigen, an antibody, an immunoconjugate, an alternative skeleton and / or a bispecific molecule) may be coated in a material to protect the compound from the action of acids and other natural conditions that may inactivate the compound. The pharmaceutical compounds according to at least some embodiments of the present invention may include one or more pharmaceutically acceptable salts. "Pharmaceutically acceptable salts" refers to salts that retain the desired biological activity of the parent compound and do not impart any adverse toxicological effects (see, for example, Berge, SM et al. (1977) J. Pharm. Sci. 66: 1-19). Examples of such salts include acid addition salts and base addition salts. Acid addition salts include those derived from non-toxic inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphorous acid, and the like, and those derived from non-toxic organic acids such as aliphatic monocarboxylic acids and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and the like. Base addition salts include those derived from alkaline earth metals such as sodium, potassium, magnesium, calcium, and the like, and those derived from non-toxic organic amines such as N,N'-dibenzylethylenediamine, N-methylglucamine, chloroprocaine, choline, diethanolamine, ethylenediamine, procaine, and the like. Pharmaceutical compositions according to at least some embodiments of the present invention may also include a pharmaceutically acceptable antioxidant. Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, and the like; (2) oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, and the like; and (3) metal chelators such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. Examples of suitable aqueous and non-aqueous carriers that can be employed in pharmaceutical compositions according to at least some embodiments of the present invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters (such as ethyl oleate). Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. Such compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers, and dispersants. Prevention of the presence of microorganisms can be ensured by the sterilization procedures described above and by the inclusion of various antibacterial and antifungal agents (e.g., parabens, chlorobutanol, phenol, sorbic acid, and the like). It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like in the composition. Furthermore, prolonged adsorption of injectable pharmaceutical forms can be achieved by the inclusion of agents that delay adsorption (e.g., aluminum monostearate and gelatin). Pharmaceutically acceptable carriers include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. The use of such media and agents for pharmaceutically active substances is known in the art. Unless any conventional media or agents are incompatible with the active compound, their use in pharmaceutical compositions according to at least some embodiments of the present invention is contemplated. Supplementary active compounds may also be incorporated into the compositions. Therapeutic compositions generally must be sterile and stable under the conditions of manufacture and storage. Compositions can be formulated as solutions, microemulsions, liposomes, or other ordered structures suitable for high drug concentrations. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, a polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol and the like), and suitable mixtures thereof. Suitable fluidity can be maintained, for example, by the use of a coating (such as lecithin), by maintaining the desired particle size in the case of a dispersion, or by the use of a surfactant. In many cases, it is preferred to include an isotonic agent, such as a sugar, a polyol such as mannitol, sorbitol, or sodium chloride, in the composition. Prolonged adsorption of injectable compositions can be achieved by including an agent that delays adsorption (e.g., monostearate and gelatin) in the composition. Sterile injectable solutions can be prepared by incorporating the desired amount of the active compound in an appropriate solvent with one or a combination of the above-mentioned ingredients, as needed, followed by sterile microfiltration. Dispersions are generally prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the required other ingredients from those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying (lyophilization), which yield a powder of the active ingredient plus any other desired ingredients from a previously sterile-filtered solution thereof. Sterile injectable solutions can be prepared by incorporating the desired amount of the active compound in an appropriate solvent with one or a combination of the above-mentioned ingredients, followed by sterile microfiltration. Dispersions are typically prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the desired other ingredients from those described above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred preparation methods are vacuum drying and freeze drying (lyophilization), which produce a powder of the active ingredient plus any other desired ingredients from its previously sterile filtered solution. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the subject being treated and the specific mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the composition that produces a therapeutic effect. Typically, within a hundred percent, this amount will be in the range of about 0.01% to about 99% active ingredient, preferably about 0.1% to about 70%, and most preferably about 1% to about 30% active ingredient in combination with a pharmaceutically acceptable carrier. The dosage regimen is adjusted to provide the optimal desired response (e.g., a therapeutic response). For example, a single bolus may be administered, several divided doses may be administered over time, or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is particularly advantageous to formulate parenteral compositions in unit dosage form for ease of administration and uniformity of dosage. As used herein, a unit dosage form refers to a physically discrete unit suitable for use in unit dosage form for a subject to be treated; each unit contains a predetermined amount of active compound calculated to produce the desired therapeutic effect in combination with the required pharmaceutical carrier. The specifications of the unit dosage forms according to at least some embodiments of the present invention are dictated by and directly depend on (a) the unique characteristics of the active compound and the specific therapeutic effect to be achieved and (b) the limitations inherent in the art regarding compounding the active compound for treating individual sensitivities. For administration of the VISTA antibodies disclosed herein, the dosage is in the range of about 0.0001 to 100 mg / kg and more typically 0.01 to 5 mg / kg of host body weight. For example, the dosage may be 0.3 mg / kg body weight, 1 mg / kg body weight, 3 mg / kg body weight, 5 mg / kg body weight, or 10 mg / kg body weight, or in the range of 1-10 mg / kg. An exemplary treatment regimen requires administration once a week, once every two weeks, once every three weeks, once every four weeks, once a month, once every three months, or once every three to six months. For the antibodies disclosed herein according to at least some embodiments of the present invention, a preferred dosing regimen includes 1 mg / kg body weight or 3 mg / kg body weight via intravenous administration, wherein the antibodies disclosed herein are administered using one of the following dosing schedules: (i) once every four weeks for six doses, followed by dosing once every three months; (ii) once every three months; (iii) 3 mg / kg body weight administered once, followed by 1 mg / kg body weight administered once every three weeks. In some methods, two or more monoclonal antibodies with different binding specificities are administered simultaneously, in which case the dosage of each antibody disclosed herein is within the ranges shown. The antibodies disclosed herein are typically administered in a variety of situations. The intervals between single administrations may be, for example, daily, weekly, monthly, every three months, or annually. Intervals may also be irregular, as indicated by measuring blood levels of antibodies to the target antigen in the patient. In some methods, the dosage is adjusted to achieve a plasma antibody concentration of about 1-1000 μg / ml, and in some methods, about 25-300 μg / ml. Alternatively, the therapeutic agent can be administered as a sustained release formulation, in which case less frequent administration is required. The dosage and frequency vary depending on the half-life of the therapeutic agent in the patient. Generally speaking, human antibodies exhibit the longest half-life, followed by humanized antibodies, chimeric antibodies, and non-human antibodies. The half-life of fusion proteins can vary widely. The dosage and frequency of administration can vary depending on whether the treatment is preventive or therapeutic. In preventive applications, a relatively low dosage is administered at relatively infrequent intervals over a long period of time. Some patients continue to receive treatment for the rest of their lives. In therapeutic applications, relatively high doses at relatively short intervals are sometimes required until the disease process is reduced or terminated and preferably until the patient shows partial or complete relief of the symptoms of the disease. Thereafter, a preventive regimen can be administered to the patient. Actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention may be varied to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient. The selected dosage level will depend on a variety of pharmacokinetic factors, including the activity of the particular composition employed in the present invention, or its ester, salt, or amide, the route of administration, the time of administration, the rate of excretion of the particular compound employed, the duration of treatment, other drugs, compounds, and / or materials used in combination with the particular composition employed, the age, sex, weight, condition, general health, and previous medical history of the patient being treated, and similar factors well known in the medical arts. Having described the present invention, the following examples are provided to further illustrate the present invention and its inherent advantages. Examples Example 1: Screening of Immunosuppressive Anti-Mouse VISTA Abs Using the Assay The present inventors developed various assays to screen for hypothetical agonistic anti-mouse VISTA antibodies. As shown in Figure 1, in vitro and in vivo screening assays were used to identify immunosuppressive anti-VISTA mAbs. In the experiment in Figure 1A, purified T cells were coated on top of anti-CD3 for 72 hours in the presence of the mAb shown. Proliferation was measured by H3 merging. In the experiment in Figure 1B, purified DO11.10 T cells were stimulated by ISQ pulsed APC for 6 days in the presence of the antibody shown. Proliferation was measured by using CTV diluted dye. In the experiment in Figure 1C, GVHD was induced by transferring C57BL / 6 cells into irradiated BALB / c recipients. Mice were injected intraperitoneally (IP) with 200 μg of antibody on day 0, day 2, and day 4 after transfer, and survival was analyzed. In the experiment in FIG. 1D , mice were treated with 10 mpk of the indicated antibodies 3 hours prior to administration of ConA (15 mpk), and IL-2 was analyzed in plasma by Luminex at 6 . More specifically, in the first analysis, CD4 +T cells were cultured with Ab1, Ab2 or Ab3 and then added to anti-CD3 coated culture dishes. After 3 days of culture, cells were pulsed with tritiated thymidine, which was incorporated by causing cell proliferation. It should be noted that both Ab1 and Ab2 induced a significant reduction in the proliferation rate of T cells, while Ab3 was useless (Figure 1). In a similar analysis in which antigen-pulsed APCs were used to stimulate transgenic T cells, T cell activation was measured by dilution of the proliferation dye. Similar to the anti-CD3 analysis, Ab1 inhibited approximately 50% of antigen-specific T cell proliferation (Figure 1B). These data show that Ab3 mAb blocks mVISTA function (i.e., enhances immune response), while Ab1 and Ab3 stimulate mVISTA function and downregulate important immune responses. We also determined whether Ab3 and Ab1 can be distinguished using an in vivo animal model, especially in GVHD and ConA hepatitis models. Mice with GVHD treated with a control antibody (Ham Ig) suffered from progressive disease and needed to be euthanized 4 weeks after transplantation as expected (Fig. 1C). Mice treated with Ab3 were also susceptible to GVHD, and in fact most mice died before the control treatment group, indicating that Ab3 can worsen the disease. On the contrary, all mice treated with Ab1 did not show obvious GVHD symptoms and almost all remained healthy for at least 40 days. Especially in these experiments, mice with GVHD treated with a control antibody (Ham Ig) suffered from progressive disease and needed to be euthanized 4 weeks after transplantation as expected (Fig. 1C). Mice treated with Ab3 were also susceptible to GVHD, and in fact most mice died before the control treatment group, indicating that Ab3 can worsen the disease. On the contrary, all mice treated with Ab1 did not show obvious GVHD symptoms and almost all remained healthy for at least 40 days. In the ConA model, the inventors tested whether each VISTA antibody affects the well-characterized T cell cytokine response to ConA. It should be noted that Ab1 induces reduced plasma cytokine levels of IL-2, but Ab3 does not ( FIG. 1D ). Specifically, in the ConA model, the inventors further tested whether each VISTA antibody affects the well-characterized T cell cytokine response to ConA. It should be noted that Ab1 induces reduced plasma cytokine levels of IL-2, but Ab3 does not ( FIG. 1D ). Therefore, these results show that anti-VISTA mAb (Ab1 and Ab2) is immunosuppressive and it has also been confirmed that these immunosuppressive anti-mouse VISTA antibodies can be distinguished from inflammatory immunosuppressive anti-mouse VISTA antibodies (Ab3). As shown in Figure 1, Ab1 is effective (immunosuppressive) in a variety of inflammatory models, including GVHD, NZB / W F1 lupus-like glomerulonephritis, concanavalin A (ConA)-induced hepatitis, collagen antibody-induced arthritis (CAIA) and imiquimod-induced psoriasis. In each of these diseases, administration of Ab1 during the course of the disease greatly reduces symptoms and / or mortality. Each model listed has unique requirements for T cells used for disease progression. Both GVHD and ConA are driven by Th1 T cell responses. Example 2: Identification of anti-VISTA Abs that suppress autoimmunity in different autoimmune disease models In the experiments in Figures 2A-F, the effects of different anti-mouse VISTA Abs in different disease models were compared again. In the experiment in Figure 2A, NZB / W F1 mice were treated with Ab1 or Ham Ig (200 μg) 3 times a week starting from week 25 until the end of the experiment. "X" indicates the time point when all the control treatment groups were sacrificed. In the experiment in Figure 2B, mice were treated with 200 μg of antibody 3 hours before administration of 15 mg / kg (mpk) ConA and survival was tracked for 80 hours. In the experiment in Figure 2C, mice were treated with collagen II mAb followed by LPS and arthritis was measured by measuring paw swelling. In these experiments, Ab1 and Ham-Ig (200 μg) were administered 3 times every other day. In the experiment in Figure 2D, imiquimod was applied to the mouse ears every day. On day 14, Ab1 or Ham-Ig (200 μg) was administered every other day and ear thickness was measured with a caliper. In the same experiment in Figure 2E-F, imiquimod was applied daily to the back of the mice. On day 9, the mice were euthanized and the skin was sectioned and stained for CD3 expression by IHC. As shown in Figures 2A-F, in each of these experimental models, administration of Ab1 during the course of a particular disease greatly reduced morbidity and / or mortality. Each model listed has unique requirements for the T cells used for disease progression. Both GVHD and ConA are driven by a Th1 T cell response. Imiquimod-induced psoriasis is an IL-17 / 23 driven disease in which T cells are recruited to the dermis. Ab1 activates CD3 +The cell number was drastically reduced (Figure 2E and F), but there was no effect on the T cell population in the spleen (data not shown), indicating that this anti-mouse VISTA Ab preferentially suppressed immunity in inflamed lesions. NZB / W F1 lupus is a multifactorial disease with contributing factors from B cells, T cells, and myeloid cells. In this model, therapeutic administration of Ab1 reduced proteinuria levels, indicating reduced damage to the kidneys. Finally, CAIA does not involve adaptive immunity, but is instead driven by macrophages and granulocytes. The inhibitory effect of anti-VISTA in this model may also affect the bone marrow compartment. Therefore, the inhibitory VISTA mAb appears to mediate the effects on T cells and the innate immune compartment. Therefore, as shown in Figures 1 and 2, single hamster anti-mouse VISTA Abs Ab1 and AB2 induced a significant decrease in the proliferation rate of T cells, while Ab3 was useless (Figure 1). In a similar analysis of transgenic T cells stimulated with antigen-pulsed APC, T cell activation was measured by proliferation dye dilution. Similar to the anti-CD3 analysis, Ab1 inhibited approximately 50% of antigen-specific T cell proliferation (Figure 1B). These data show that Ab1 and Ab2 stimulate VISTA function and thereby downregulate important immune responses. Specifically, Ab1 (a hamster anti-mouse VISTA antibody) is effective in a variety of inflammatory models, including GVHD, NZB / W F1 lupus-like glomerulonephritis, concanavalin A (ConA)-induced hepatitis, collagen antibody-induced arthritis (CAIA), and imiquimod-induced psoriasis (Figures 1 and 2). In each of these diseases, administration of Ab1 during the course of the disease greatly reduces symptoms and / or mortality. Each of the models listed has unique requirements for T cells used for disease progression. Both GVHD and ConA are driven by Th1 T cell responses. As mentioned above, imiquimod-induced psoriasis is a disease driven by IL-17 / 23, in which T cells are recruited to the dermis of the skin. Therefore, the inhibitory effect of Ab1 in this specific autoimmune model indicates that this antibody can also affect the bone marrow compartment. Therefore, these immunosuppressive anti-mouse VISTA mAbs appear to mediate effects on T cells and innate immune compartments. Example 3: Development of human VISTA knock-in mice for screening agonistic anti-human VISTA Abs Previous examples were about the isolation and characterization of agonistic anti-mouse VISTA Abs. No agonistic anti-human VISTA Abs have been reported in the literature to date. Nevertheless, the assignee of the present invention and other groups have identified a large number of antagonistic anti-human VISTA antibodies. Therefore, before the present invention, it was not certain whether agonistic anti-human VISTA antibodies would be identified. Such antibodies will be highly beneficial because there are currently no approved human therapeutics that use the natural function of NCR to suppress immune responses. Although Orencia (CTLA4-Ig) is effective, it only works by blocking the CD28-B7 interaction and pathway, and does not work by stimulating the downregulation pathway. As illustrated by the effective immunosuppressive effects of two different agonist anti-VISTA mAbs shown in the Examples below, the involvement of this pathway may prove to be a revolution in the management of different human autoimmune diseases. In addition, the immunosuppressive effects of anti-VISTA on adaptive and innate autoimmune effector mechanisms make it different from many other anti-inflammatory agents. With respect to the above, it is assumed that the necessary and required reagent in screening for agonistic anti-human VISTA Abs is human VISTA knock-in mice. The assignee of the present invention has produced human VISTA knock-in mice ("hV-KI mice"). These hV-KI mice express human VISTA instead of mouse VISTA. Specifically, as shown in FIG3 , CD4 + T cells, CD8 + T cells, Treg (CD4 + FoxP3 + ) and monocytes, CD11b + 、Ly6C + 、Ly6G - Lymph nodes from WT and VISTA KI mice were isolated and stained with αVISTA antibodies against mouse or human proteins, respectively. The expression pattern of hV-KI was the same as that seen in WT mice, as CD4 + and CD8 + T cells, regulatory T cells, and monocytes expressed consistent amounts of surface protein between the two strains (see Figure 3). In addition, hV-KI mice did not develop any signs of inflammatory disease observed in VISTA KO mice, indicating that hVISTA is fully functional in the mouse immune system (treatment not shown). Therefore, this mouse model can be used for different analyses to screen immunosuppressive mAbs. Example 4: Synthesis of hypothetical agonistic anti-human VISTA antibodies Figure 4 contains the sequences of different anti-human VISTA antibodies. These antibodies specifically bind to human VISTA (e.g., VSTB49-VSTB116) and possess VISTA antagonist properties, i.e., when in IgG1 format, these antibodies inhibit the inhibitory effect of VISTA on immunity, e.g., when the antibodies comprise a wild-type IgG1 Fc region, i.e., unmodified. The antibody identified in Figure 4 is specifically 1E8. This murine anti-human VISTA antibody comprises the variable heavy and light chain polypeptides listed below and was converted by the inventors into two human chimeric forms. The first chimeric antibody, referred to herein as INX800, was obtained by linking human IgG2 heavy and light chain constant region polypeptides to 1E8 variable heavy and light chain polypeptides. In this first chimeric antibody, no amino acid residues within the IgG2 constant region were modified. A second chimeric antibody, referred to herein as INX801, was similarly obtained by linking human IgG2 heavy and light chain constant region polypeptides to 1E8 variable heavy and light chain polypeptides. In this second chimeric antibody, the cysteine ​​residue at position 127 in the human IgG2 kappa chain was converted to serine. In addition, no amino acid residues in the IgG2 constant region were modified. H Polypeptide EVKLLESGGGLVQPGGSLKLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEVYPDSSTINYTPSLKDKFIISRDNAKNTLYLQMIKVRSEDTALYYCARGRGDYWGQGTSVTVSS(SEQ ID NO:57) IE8 V L Polypeptide DIQMTQSPASLSASVGETVTITCRASGNIHNYLSWYHQKQGKSPQLLVYNAKTLADGVPSRFSGSGSGTQYSLKINSLQPEDFGSYYCQNFWSTPFTFGSGTKLEIKR. (SEQ ID NO: 58) Example 5: Evaluation of putative agonistic anti-human VISTA antibodies in the ConA animal model The effects of a chimeric IgG2 antibody and a control antibody were compared in a concanavalin A hepatitis model. In this in vivo model, different animals were pre-administered with 10 mg / kg of a chimeric IgG2 antibody (INX800 or INX801) or a control antibody 3 hours prior to concanavalin A administration. Three hours after antibody administration, mice were subsequently administered ConA at 12 mg / kg. Blood was then collected from these animals and controls 6 hours after ConA administration by cardiac puncture. All animals performed well, with no significant morbidity or mortality. The blood was then analyzed for cytokine expression. Specifically, a 32-plex was run using plasma obtained from collected blood samples using conventional methods and a conventional cytokine test kit for cytokine analysis. As shown in Figure 5, the expression of several proinflammatory cytokines in animals administered with INX800 or INX801 antibodies was significantly suppressed compared to control animals. Specifically, GM-CSF, IL-2, IL-4, IL-6, IL-17, and TNF-α levels in animals treated with INX800 or INX801 were all significantly lower compared to controls. The [reduction] expression of these cytokines was substantially the same in animals treated with INX800 or INX801. Furthermore, the expression of certain chemokines (keratinocyte-derived chemokine or "KC") and macrophage inflammatory protein 2 (MIP-2) was substantially increased in animals treated with INX800 or INX801 compared to controls. Furthermore, the [increased] expression of these proteins was substantially the same in animals treated with INX800 or INX801. Based on these results, both INX800 and INX801 appear to be effective VISTA agonists as they appear to elicit similar immunosuppressive effects as VISTA elicits on the expression of various inflammatory cytokines. Example 6: Evaluation of putative agonistic anti-human VISTA antibodies in an animal model of graft-versus-host disease (GVHD) The effects of the same hypothetical agonistic anti-human VISTA antibodies, INX800 and INX801, were also compared in a graft-versus-host disease (GVHD) animal model compared to untreated animals or controls treated with unrelated antibodies. In this animal model, T cells are transferred into irradiated hosts and body weight is measured as a readout of the disease. Based on the GVHD disease process, all control mice (8 / 8) had to be euthanized. The results of these animal studies are shown in Figure 6. As shown, none of the mice treated with INX800 or INX801 [0 / 8] needed to be euthanized because GVHD was suppressed to a considerable extent due to treatment with INX800 or INX801 antibodies. Based on these results, INX800 and INX801 appear to be effective VISTA agonists because they appear to effectively suppress the GVHD immune response. Example 7: Effects of hypothetical ago...

Claims

1. An isolated or recombinant human or humanized antibody comprising an antigen-binding region specifically binding to a human V domain Ig repressor factor (human VISTA) activated on T cells, wherein the antibody antagonizes or blocks the immunosuppressive effect of VISTA on pro-inflammatory cytokine expression or T cell proliferation, and wherein the antibody comprises a human IgG1 Fc or constant region, wherein the isolated or recombinant human or humanized antibody comprises the VH CDR of SEQ ID NO:200, 201 and 202 and the VL CDR (INX904 or VSTB103) of SEQ ID NO:203, 204 and 205.

2. The isolated or recombinant human or humanized antibody as claimed in claim 1, comprising the VH polypeptide of SEQ ID NO:206 and the VL polypeptide of SEQ ID NO:

208.

3. The isolated or recombinant human or humanized antibody as claimed in claim 1 or 2, wherein the human IgG1 Fc or constant region contains a mutation that impairs FcR binding.

4. A pharmaceutical composition comprising at least one isolated or recombinant human or humanized antibody as claimed in any one of claims 1 to 3.

5. Use of at least one of the isolated or recombinant human or humanized antibodies of any one of claims 1 to 3 in the preparation of a medicament for the treatment of cancer or infection.

6. As claimed in claim 5, wherein the drug comprises another immunomodulatory antibody or an immunomodulatory fusion protein.

7. As claimed in claim 5 or 6, wherein the drug is used in combination with another drug that comprises another immunomodulatory antibody or an immunomodulatory fusion protein.

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