The invention provides a modified CXCL10 polypeptide, comprising an insertion of an additional amino acid at the N-terminus of a corresponding wild type CXCL10, pharmaceutical composition comprising the same and method for using thereof for treating cancer.

Provided herein are IL-21 muteins and fusion proteins comprising the same for use in methods of treating a disease. Related conjugates, nucleic acids, vectors, host cells, pharmaceutical compositions and kits are also provided herein. Methods of making the IL-21 muteins and fusion proteins comprising the same, as well as methods of treating a subject in need thereof, are provided by the present disclosure. Further provided are PD-1 antigen-binding proteins.

Immunomodulatory nanofilaments are provided which present immune factors, especially cytokines, to immune cells, particularly T cells, so as to modulate the immune response of said cells. Methods of using such nanofilaments are also provided.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Antibodies that bind ICOS (Inducible T cell Co-Stimulator). Therapeutic use of anti-ICOS antibodies for modulating the ratio between regulatory T cells and effector T cells, to stimulate the immune system of patients, including use in treating cancers. Methods of producing anti-ICOS antibodies, including species cross-reactive antibodies, using transgenic knock-out mice.

Provided are activatable proprotein homodimers, comprising at least two separate polypeptide chains, each chain comprising an IL-2 protein variant that has reduced binding affinity to wild-type IL-2Rα relative to that of the wild-type IL-2 sequence, a cleavable linker, and an IL-2 binding protein, among other optional features, and related pharmaceutical compositions and methods of use thereof.

The present invention provides, inter alia, treatment regimens for administration of an IL-2 receptor agonist. The present invention is directed to, inter alia, methods for modulating an immune response in a subject in need thereof with an IL-2 receptor agonist. In some aspects, the immune response is an anti-cancer immune response.

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

The present application relates to novel prodrugs of IL-12. Further included in the present application are methods of making and using the novel prodrugs.

The present disclosure provides a cytokine-based bioactivatable drug construct (“VitoKine”) platform that aims to reduce systemic mechanism-based toxicities and lead to broader therapeutic utility for proteins and cytokines such as IL-15 and IL-2 for the treatment of cancer, autoimmune diseases, inflammatory diseases, viral infection, transplantation and various other disorders. The novel VitoKine constructs of the present invention comprise: 1) a tissue or disease site targeting moiety D1 domain (“D1”), 2) a bioactivatable moiety D2 domain (“D2”), and a concealing moiety D3 domain (“D3”). Importantly, because the “active moiety” of the VitoKine construct will remain inert until activated locally by proteases that are upregulated in diseased tissues, this will limit binding of the active moiety to the receptors or to the targets in the peripheral or on the cell-surface of non-diseased cells and tissue to prevent over-activation of the pathway and reduce undesirable “on-target” “off tissue” toxicities. Additionally, the inertness of the VitoKine active moiety prior to protease activation will significantly decrease the potential antigen or target sink, and thus, prolong the in vivo half-life and result in improved biodistribution, bioavailability and therapeutic efficacy.