Abstract: The present invention provides a bispecific biologic comprising a ligand specific for CTLA-4 and a ligand specific for a pMHC complex.

Abstract: In some embodiments, described herein is a method of tumor treatment or tumor vaccination. The method generally comprises applying to a human being in need thereof a tumor therapeutic composition or tumor vaccine defined herein. The tumor therapeutic composition or tumor vaccine can be produced by protein transfer of glycosyl-phosphatidylinositol (GPI)-anchored immunostimulatory or costimulatory molecules.

Abstract: Disclosed soluble PD-1 (sPD-1) proteins and nucleic acids, and therapeutic compositions comprising sPD-1 proteins and nucleic acids, for enhancing immunity of a subject against coronavirus infection. Disclosed are soluble PD-1 fusion proteins that include a soluble PD-1 protein fragment and an antigenic protein fragment, preferably where the antigenic protein fragment comprises a coronavirus protein fragment. In some forms, the coronavirus protein fragment is derived from a coronavirus receptor binding domain (RBD) or a coronavirus nucleoprotein (N). In some forms, the sPD-1 proteins, nucleic acids, and compositions are formulated as a vaccine composition. Also disclosed are methods for treating a subject at risk of or suffering a coronavirus infection.

Abstract: Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.

Abstract: The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Abstract: Disclosed are compositions and methods for targeted treatment of CD123-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CD123-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CD123-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Provided is a fusion protein dimer using an antibody Fc region as the backbone, comprising a first and a second polypeptide chain. The first polypeptide chain comprises a first antibody Fc region and one or more single-domain antibodies fused to the first antibody Fc region. The second polypeptide chain comprises a second antibody Fc region and one or more single domain antibodies fused to the second antibody Fc region. The first polypeptide chain and/or the second polypeptide chain further comprise a cytokine fused to the Fc region of the respective antibody. Further provided is use of the fusion protein dimer in preparing an immunotherapeutic drug for treating tumors. The Fc fusion protein heterodimer not only increases the activity of a single domain antibody, but also significantly improves the biological activity of a cytokine.

Abstract: The present invention relates to humanized antibodies that specifically bind to human BTN3A and their use in treating cancer and infectious disorders.

Abstract: Genetically engineered hematopoietic cells such as hematopoietic stem cells having one or more genetically edited genes of lineage-specific cell-surface proteins and therapeutic uses thereof, either alone or in combination with immune therapy that targets the lineage-specific cell-surface proteins.

Abstract: Provided are constructs comprising a single-domain antibody (sdAb) moiety that specifically recognizes TIGIT. Also provided are methods of making and using these constructs.

Abstract: It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Abstract: Methods are provided for predicting a response to an anti-PD-1 antibody or anti-PD-L1 antibody therapy based on a new biomarker and for evaluating a malignancy of cancer. The method for predicting a response of a subject to an anti-PD-1 antibody or anti-PD-L1 antibody therapy includes measuring an expression level of LAT1 in a sample collected from a cancer tissue of the subject; and predicting a response of the subject to the anti-PD-1 antibody or anti-PD-L1 antibody therapy based on the expression level of LAT1. The method for evaluating a malignancy of cancer in a subject includes staining a sample collected from a cancer tissue of the subject with an anti-LAT1 antibody and an anti-PD-L1 antibody; and evaluating a malignancy of the cancer in the subject based on a presence or absence of a LAT1-positive and PD-L1-positive site.

Abstract: The present disclosure relates to the finding that the ratio of circulating (i.e., peripheral blood) central memory T cells to circulating effector T cells in a cancer patient can predict whether a tumor has an inflammatory milieu or not. In addition, since having an inflammatory milieu (“hot tumor”) is a positive factor for responding to checkpoint inhibitors, e.g., PD-1 antagonists, this assay on peripheral blood can also be used to predict a response to a checkpoint inhibitor, e.g., an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity or an antibody or an antigen binding portion thereof that binds specifically to PD-1 ligand 1 (PD-L1) and inhibits PD-L1 activity.

Abstract: A monoclonal antibody or a derivative thereof that binds to a human TIGIT antigen with high-affinity and antagonistically inhibits the binding of TIGIT to a ligand thereof such as CD155 is provided. Amino acid sequences of antigen complementarity-determining regions CDR-L1, CDR-L2 and CDR-L3 of an antibody light chain variable region, and amino acid sequences of antigen complementarity-determining regions CDR-H1, CDR-H2 and CDR-H3 of an antibody heavy chain variable region are specified. Further, a humanization preparation method for the antibody and amino acid sequences of the heavy chain variable region and light chain variable region of the humanized antibody are provided. The antibody or the derivative thereof can serve as an ingredient of a pharmaceutical composition or can be prepared into an appropriate drug preparation, and administered alone or in combination with other medications, such as an anti-PD-1 monoclonal antibody, or treatment means, for treating diseases such as tumors.

Abstract: The present application relates to anti-PD-L1 antibodies or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, for the treatment of and cancer.

Abstract: The present invention relates to a method of treating an autoimmune or inflammatory disease or a neurodegenerative disease with an antibody to CD154.

Abstract: A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session of non-treatment.

Abstract: A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.

Abstract: There is disclosed compositions and methods relating to or derived from anti-PD-L1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-L1, PD-L1-binding fragments and derivatives of such antibodies, and PD-L1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having PD-L1 related disorders or conditions, including various inflammatory disorders and various cancers.

Abstract: The invention relates to chimeric antigen receptors (CAR) that comprise one or more single human variable domain antibody and cells that express such CAR. In particular, the invention relates to CARs that include multiple single human variable domain antibodies. In a particular embodiment, the one or more single human variable domain antibody binds to prostate membrane antigen.