Abstract: The present application relates to immunomodulatory molecules comprising a first binding domain (e.g., immunostimulatory cytokine such as IL-2 or IL-12 or variant thereof) specifically recognizing a first target molecule (e.g., receptor of immunostimulatory cytokine) and a second binding domain (e.g., agonist ligand such as PD-L1 or PD-L2 or variant thereof, or agonist antigen-binding fragment such as anti-PD-1 agonist Fab, scFv, VHH, or full-length antibody) specifically recognizing a second target molecule (e.g., inhibitory checkpoint molecule such as PD-1), wherein the first binding domain upon binding to the first target molecule up-regulates an immune response, and wherein the second, binding domain upon binding to the second target molecule down-regulates the immune response. Methods of making and uses of such immunomodulatory molecules are also provided.

Abstract: The present application relates to immunocytokines comprising a cytokine or variant thereof positioned at the hinge region of a heavy chain of an antibody (e.g., full-length antibody), or positioned at a hinge region between an antigen-binding fragment (e.g., ligand, receptor, or antibody fragment) and an Fc domain subunit or portion thereof, methods of making, and uses thereof.

Abstract: The present application relates to immunocytokines comprising a cytokine or variant thereof positioned at the hinge region of a heavy chain of an antibody (e.g., full-length antibody), or positioned at a hinge region between an antigen-binding fragment (e.g., ligand, receptor, or antibody fragment) and an Fc domain subunit or portion thereof, methods of making, and uses thereof.

Abstract: The disclosure provides for compositions, methods, and kits for evaluating the effect of a cell-killing agent on a population of tumor cells (e.g., tumor cells that can inducibly express reporter protein).