The disclosure provides a chimeric antigen receptor (CAR) comprising a modified hinge, transmembrane and/or intracellular domain disclosed herein. Some aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) comprising the costimulatory domain disclosed herein. Other aspects of the disclosure relate to cells comprising the CAR and use in a T cell therapy.

Fusion compounds and methods of using same are provided which bind and neutralize human receptor activator of nuclear factor kappa-B ligand and are agonistic to parathyroid hormone receptor 1 signaling, said compounds are useful as agents for bone healing or treating conditions associated with bone mass loss or degeneration including treating osteoporosis.

The present invention relates to multispecific antibodies against a novel targets' combination of CD7 and CD9, and their use in the treatment of cancer and infectious diseases.

The inventors now provide novel IL-15/IL-15 receptor alpha (IL-15Rα) fusion proteins. Furthermore, as a complement to anti-PD-1 therapy, the inventors developed a series of anti-PD-1/IL-15/IL-15 receptor alpha (IL-15Rα) immunocytokines that are able to simultaneously target multiple steps in the immune activation process. The development of said immunocytokines provides the potential benefits associated with anti-PD-1 antibodies and IL-15 administered individually with several distinct advantages. These include a significantly extended in vivo half-life relative to the IL-15 therapy, administration of a pre-formed IL-15/IL-15Rα complex that would preclude the need for IL-15Rα trans-presentation, high activity leading to a low target therapeutic dose and targeted delivery of IL-15 to regions with high PD-1 cells that will limit off-target adverse events.

Embodiments of the present disclosure relate generally to the treatment of cancer involving activation of the tumor necrosis factor-related apoptosis inducing ligand receptor (TRAILR) pathway. In particular, the present disclosure provides compositions and methods for the identification of genes conferring TRAIL resistance, and the development of rational drug combinations targeting these genes. The therapeutic drug combinations of the present disclosure function synergistically to sensitize cancer cells to TRAIL-resistant cancers.

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.

The present invention provides fusion polypeptides for inhibiting angiogenesis, fusion protein nanocages having peptides for inhibiting angiogenesis, and diagnostic and therapeutic (theranostic) uses thereof.

The invention relates to novel TNF family ligand trimer-containing antigen binding molecules having at least one moiety capable of specific binding to PD1 and a first and a second polypeptide that are linked to each other by a disulfide bond, the first polypeptide having two ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by a peptide linker and the second polypeptide having a single ectodomain of the same TNF ligand family member or a fragment thereof.

The present invention relates to fusion proteins comprising a binding protein and an IL-15 polypeptide as well as uses thereof, pharmaceutical compositions comprising such fusion proteins and a method for producing such fusion proteins.

Methods and compounds for conferring site-specific or local immune privilege.