Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and/or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and/or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.

Abstract: The present invention is directed to PVRIG polypeptides and their uses.

Abstract: An active form (BY-001) of a homomultimeric chimeric protein PD-L1/Fc-gammal may have a composition of 25% dimer, 30% tetramer and 45% hexamer. BY-001 consists of two distinct functional domains at the aggregated state, one is the extracellular domain of PD-L1 and another one is the IgG1 Fc region. Accordingly, the first functional domain of PD-L1 at its aggregated state is more effective in suppressing the activity of CD3+ and CD28+ T cells; while, on the other hand, the second functional domain of FC-gammal at its aggregated state exerts only the suppressive effects on the immune cell bearing the Fc-gamma receptors. Thus, the features provided in present invention indicate that BY-001 regulates the functions of immune cells subsets that are responsible for the peripheral immune tolerance, which makes BY-001 potential to help restore or maintain the peripheral immune tolerance in patients with autoimmune diseases or in recipients of allografts.

Abstract: The present disclosure provides antibodies, including antibody fusions, which specifically bind to human PD-L1 protein (huPD-L1) and are capable of decreasing, inhibiting, and/or fully-blocking immune regulatory effects mediated by PD-L1, such as binding to the immune checkpoint molecule PD-1 in the tumor microenvironment. Additionally, the antibodies include fusions with the cytokine inhibitory factor, IL10, which can replenish and/or activate CD8+ T-cell cytotoxicity in the tumor microenvironment. The present disclosure also provides methods of using the antibodies (and compositions thereof) to treat diseases and conditions responsive to decreasing, inhibiting and/or blocking immune regulatory function or activity mediated by PD1 binding to PD-L1.

Abstract: Disclosed herein are methods and compositions including antigen-binding polypeptides comprising a stalk region and a stalk extension region. In some cases, the antigen-binding compositions comprising the stalk extension region has increased expression on a cell surface and, in some cases, has increased antigen-binding efficiency. A subject antigen binding polypeptide can be a chimeric antigen receptor (CAR).

Abstract: B7-H5 costimulatory polypeptides, nucleic acids encoding such polypeptides, and methods for using the polypeptides and nucleic acids to enhance a T cell response are provided herein.

Abstract: The present invention is directed to a peptide, multimer, conjugate, analog, derivative or mimetic thereof that inhibits the activity of VISTA. The invention further contemplates therapeutic use of the VISTA antagonist peptide, multimer, conjugate, derivative or mimetic thereof, including treating or preventing cancer, bacterial infections, viral infections, parasitic infections and fungal infections, as well as research uses of the antagonist.

Abstract: The present invention relates, in part, to chimeric proteins that bind a non-cellular structure and their use as therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the chimeric proteins and their use in the treatment of various diseases.

Abstract: Methods and compounds for conferring site-specific or local immune privilege, such as targeting to a cell expressing MAdCAM.

Abstract: The invention provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and Lymphocyte activation 3 (LAG 3) mediated inhibition in a PD-1 and/or LAG3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and/or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3, thereby inhibiting PD-1 and/or LAG3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3.

Abstract: Disclosed are compounds for use in modulating immune responses. More particularly, the present invention discloses oligomeric forms of PD-L2 for use in modulating Th1 immune responses. The compounds of the present invention find utility in a range of Th1-mediated disorders including pathogenic infections and hyperproliferative disorders.

Abstract: The present invention relates to methods of treating hematologic cancers using a combination of inhibitors of PD-1 or PD-L1 and TIM-3, LAG-3 or CTLA4.

Abstract: PD1-41BBL fusion proteins are provided. Accordingly, there is provided a PD1-41BBL fusion protein comprising a single amino acid linker between the PD1 and the 41BBL. Also there is provided a PD1-41BBL fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-41BBL fusion protein, host-cells expressing the PD1-41BBL fusion protein and methods of use thereof.

Abstract: The present invention relates to a chimeric molecule useful in adoptive cell therapy (ACT), and cells comprising the same. The chimeric molecule can act as a modulator of cellular activity enhancing responses when an endogenous T-cell receptor (TCR) is engaged with its cognate antigen. The present invention also provides proteins, nucleic acids encoding the chimeric molecule and therapeutic uses thereof.

Abstract: The present invention provides antibodies that bind to the T cell co-inhibitor lymphocyte activation gene 3 (LAG3) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to LAG3. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing LAG3 activity, thus providing a means of treating a disease or disorder such as cancer or viral infection.

Abstract: Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.

Abstract: The invention provides antagonistic and agonistic anti-human VISTA antibodies and antibody fragments. These antagonist antibodies and antibody fragments may be used to inhibit or block VISTA's suppressive effects on T cell immunity and thereby promote T cell immunity. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These antagonist antibodies and antibody fragments are especially useful in the treatment of cancer and infectious conditions. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

Abstract: The present invention provides methods for increasing expression of ICOS on an effector T cell comprising contacting said effector T cell with an anti-PD-1 antibody. The present invention also provides methods for decreasing expression of ICOS on a regulatory T cell comprising contacting said regulatory T cell with an anti-PD-1 antibody. The present invention provides methods for increasing sensitivity to an agent directed to ICOS in a human comprising administering to the human an anti-PD1 antibody. The present invention also provides methods of treating cancer in a human in need thereof comprising administering an anti-PD-1 antibody and an anti-ICOS antibody to said human, wherein the anti-PD-1 antibody increases T cell sensitivity to the ICOS antibody.

Abstract: The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.

Abstract: Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of Fc?RI?. Notably, CAR constructs with an intracellular domain of Fc?RI? had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.