Abstract: The present disclosure relates to methods of increasing the efficacy of adoptive cell therapy (ACT) and methods of treating cancer, wherein the methods include administering to a subject with cancer in need thereof a combination therapy comprising a therapeutically effective amount of an ACT (e.g., an immune cell comprising a modified T cell receptor (TCR) against a tumor-associated antigen (TAA), or a chimeric antigen receptor (CAR) against a TAA) and a therapeutically effective amount of a targeted immunocytokine (e.g., a fusion protein comprising an IL2 moiety and an immunoglobulin antigen-binding domain that binds to PD1). The combination therapy demonstrates increased anti-tumor efficacy, increased duration of tumor control and/or increased overall survival, as compared to a subject administered the ACT as monotherapy or the ACT in combination with a non-targeted immunocytokine.

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: This disclosure relates to IL-2 variants and methods of use thereof, including methods of treating or inhibiting a cancer or tumor. The IL-2 variants may have reduced ability in binding to or activating IL-2R?. The IL-2 variants may retain the ability in binding to or activating IL-2R? and/or IL-2R??. In addition, the IL-2 variants may have decreased Treg activity but maintain the capacity to activate NK cells and T effector cells.

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 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 relates to IL-2 variants and methods of use thereof, including methods of treating or inhibiting a cancer or tumor. The IL-2 variants may have reduced ability in binding to or activating IL-2R?. The IL-2 variants may retain the ability in binding to or activating IL-2R? and/or IL-2R??. In addition, the IL-2 variants may have decreased Treg activity but maintain the capacity to activate NK cells and T effector cells.

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: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: The present disclosure relates to IL27 receptor agonists with improved therapeutic profiles.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

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

Abstract: The present disclosure relates to a fusion protein comprising an antigen-binding moiety that binds specifically to human PD-1 and an IL2 moiety, and methods of use thereof.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: Cyclic-GMP-AMP synthase (cGAS) and cyclic-GMP-AMP (cGAMP), including 2?3-cGAMP, 2?2-cGAMP, 3?2?-cGAMP and 3?3?-GAMP, are used in pharmaceutical formulations (including vaccine adjuvants), drug screens, therapies, and diagnostics.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: This disclosure relates to IL-2 variants and methods of use thereof, including methods of treating or inhibiting a cancer or tumor. The IL-2 variants may have reduced ability in binding to or activating IL-2R?. The IL-2 variants may retain the ability in binding to or activating IL-2R? and/or IL-2R??. In addition, the IL-2 variants may have decreased Treg activity but maintain the capacity to activate NK cells and T effector cells.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Abstract: The present disclosure relates to IL2 agonists with improved therapeutic profiles.