Abstract: The present disclosure relates to IL 12 receptor agonists with improved therapeutic profiles.

Abstract: The present disclosure provides bispecific antigen-binding molecules that bind to PD-L1 and CD28 (PD-L1×CD28). In certain embodiments, the present disclosure provides for a bispecific PD-L1×CD28 antigen-binding molecule (or antibody) or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds CD28, and a second antigen-binding domain that specifically binds PD-L1. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure bind CD28 on T-cells with the first antigen-binding domain and PD-L1 expressed on tumor cells or antigen presenting cells with the second antigen-binding domain. In certain embodiments, the bispecific antigen-binding molecules are capable of inhibiting growth of a tumor. The bispecific antigen-binding molecules of this disclosure are useful for treatment of cancer.

Abstract: The present disclosure provides bispecific antigen-binding molecules that bind to PD-L1 and 4-1BB (PD-L1×4-1BB). In certain embodiments, the present disclosure provides a bispecific PD-L1×4-1BB antibody or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds 4-1BB, and a second antigen-binding domain that specifically binds PD-L1. In certain embodiments, the bispecific antibodies disclosed herein bind 4-1BB on T-cells with the first antigen-binding domain and PD-L1 expressed on tumor cells or antigen presenting cells with the second antigen-binding domain. In certain embodiments, the antibodies of the present disclosure are useful in treatment of a cancer.

Abstract: The present disclosure provides interferon (IFN) receptor antagonists. IFN receptor antagonists disclosed herein comprise an anchoring moiety, an IFN masking moiety, an IFN moiety, and a separator moiety, e.g., a targeting moiety that recognizes an antigen associated with cells expressing Type 1 interferon receptors and anchors the IFN receptor antagonist to such cells. The disclosure further provides pharmaceutical compositions comprising the IFN receptor antagonists, and methods of use of the IFN receptor antagonists in IFN signaling inhibition, including treatment methods. Also disclosed are nucleic acids encoding the IFN receptor antagonists, recombinant cells that express the IFN receptor antagonists, and methods of producing the IFN receptor antagonists.

Abstract: In certain aspects, provided herein are compositions and methods for treating cancer. The methods of the present disclosure comprise administering to a subject in need thereof a NK cell expressing a CAR in combination with an antigen-binding molecule that binds to a tumor antigen, wherein the CAR-NK cell targets tumor cells through binding to the antigen-binding molecule.

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: CD38 is expressed on malignant plasma cells. CD28 is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel anti-CD38 antibodies, anti-CD28 antibodies, and bispecific antibodies (bsAbs) that bind to both CD38 and CD28 and act as costimulatory agents to activate T cells via binding CD80 and/or CD86. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma, lymphoma, and leukemia.

Abstract: The present disclosure provides interferon receptor agonists with improved safety profiles and therapeutic indices. The interferon receptor agonists are attenuated through masking and/or reduced receptor binding as compared to a wild-type interferon. IFN receptor agonists optionally further comprise a targeting moiety, e.g., a targeting moiety that recognizes a tumor- or immune cell-associated antigen and directs the interferon receptor agonist to a tumor site and/or tumor-reactive immune cells. The disclosure further provides pharmaceutical compositions comprising the interferon receptor agonists, and methods of use of the interferon receptor agonists in therapy, as well as nucleic acids encoding the interferon receptor agonists, recombinant cells that express the interferon receptor agonists and methods of producing the interferon receptor agonists.

Abstract: The present disclosure provides interferon receptor agonists with improved safety profiles and therapeutic indices. The interferon receptor agonists are attenuated through masking and/or reduced receptor binding as compared to a wild-type interferon. IFN receptor agonists optionally further comprise a targeting moiety, e.g., a targeting moiety that recognizes a tumor- or immune cell-associated antigen and directs the interferon receptor agonist to a tumor site and/or tumor-reactive immune cells. The disclosure further provides pharmaceutical compositions comprising the interferon receptor agonists, and methods of use of the interferon receptor agonists in therapy, as well as nucleic acids encoding the interferon receptor agonists, recombinant cells that express the interferon receptor agonists and methods of producing the interferon receptor agonists.

Abstract: CD38 is expressed on malignant plasma cells. CD28 is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel anti-CD38 antibodies, anti-CD28 antibodies, and bispecific antibodies (bsAbs) that bind to both CD38 and CD28 and act as costimulatory agents to activate T cells via binding CD80 and/or CD86. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma, lymphoma, and leukemia.

Abstract: CD38 is expressed on malignant plasma cells. 4-1BB is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel multispecific antigen binding molecules (MABMs) that bind to both CD38 and 4-1BB, for example, to provide “signal 2” in order to enhance the activation of T cells in the presence of a “signal 1”, provided by a Tumor-associated antigen (TAA)×CD3 bispecific antibody or an allogeneic response provided by an antigen presenting cell. In certain embodiments, the multispecific antigen binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The multispecific antigen binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present disclosure provides IL2 proproteins comprising an IL2 moiety that is masked with an IL2R? moiety and a protease-cleavable linker, configured such that the IL2R? moiety is released from the IL2 moiety upon the action of a protease, e.g., at a tumor site. The IL2 proproteins optionally further comprise a targeting moiety, e.g., a targeting moiety that recognizes a tumor-associated antigen and directs the proprotein to a tumor site. The disclosure further provides pharmaceutical compositions comprising the IL2 proproteins, and methods of use of the IL2 proproteins in therapy, as well as nucleic acids encoding the IL2 proproteins, recombinant cells that express the IL2 proproteins and methods of producing the IL2 proproteins.

Abstract: This disclosure provides methods for treating cancer and for ameliorating cytokine release syndrome in a subject with a tumor. The methods include administering to a subject in need thereof a bispecific anti-CD20/anti-CD3 antibody before administering to the subject an anti-PD-1 antibody. The disclosed methods represent effective therapies for cancer, e.g, B-cell malignancies, with mitigation of the potential life-threatening effects of cytokine release syndrome (CRS).

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen- binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16, such as ovarian tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

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: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human CD-22. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD-22, such as B-cell lymphomas. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

Abstract: The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.