Abstract: This present invention relates to BCMA binders (e.g. antibodies) and chimeric antigen receptor (CAR) constructs comprising a BCMA antigen binding molecule. The BCMA binders specifically bind to BCMA. The present BCMA CARs further comprise a hinge region (e.g., CD28 hinge), a transmembrane domain, and one or more intracellular NK cell signalling domains. NK cells expressing a BCMA CAR has increased efficacy in killing cancer cells. Provided herein also include therapeutic uses of the BCMA binders and BCMA CARs.

Abstract: The present invention provides, among other things, a masked cytokine comprising an attenuated interleukin 2 (IL-2) polypeptide, a VHH masking moiety, a carrier moiety and anti-PD1 targeting moiety. In some embodiments, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Abstract: The present invention relates to an VHH masked cytokines, comprising an IL-2 polypeptide, an anti-IL-2 VHH masking moiety and a proteolytically cleavable peptide. The anti-IL-2 VHH masking moiety masks IL-2 reducing or preventing binding of the cytokine or functional fragment thereof to its cognate receptor. Upon proteolytic cleavage at a target site, the IL-2 becomes activated, which renders it capable or more capable of binding to its cognate receptor.

Abstract: This present invention relates to BCMA binders (e.g. antibodies) and chimeric antigen receptor (CAR) constructs comprising a BCMA antigen binding molecule. The BCMA binders specifically bind to BCMA. The present BCMA CARs further comprise a hinge region (e.g., CD28 hinge), a transmembrane domain, and one or more intracellular NK cell signalling domains. NK cells expressing a BCMA CAR has increased efficacy in killing cancer cells. Provided herein also include therapeutic uses of the BCMA binders and BCMA CARs.

Abstract: This invention relates to binding molecules that bind specifically to TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) and cadherin-17 (CDH17) and their use in medicine, pharmaceutical compositions comprising the same, and methods of using the same as agents for treatment and/or prevention of cancer.

Abstract: The present disclosure relates to cleavable carriers and cleavable carrier-linked cytokine prodrugs wherein the cleavable carrier is an engineered Fc domain comprising at least one tumor-associated protease cleavage site. Upon cleavage at the cleavage site of the carrier Fc domain, the cytokine is released from a masking moiety. The platform provides enzymatically induced prodrug activation. The present disclosure further provides pharmaceutical compositions comprising said cleavable carrier-linked cytokine prodrugs, their use as a medication as well as methods of treatment of diseases and administration.

Abstract: The present invention relates to targeted, masked cytokines, comprising a cytokine or functional fragment thereof, a masking moiety, a targeting moiety and a proteolytically cleavable linker. The targeting moiety comprises an antigen-binding moiety that specifically binds to an antigen expressed on the surface of a target cell The masking moiety masks the cytokine or functional fragment thereof thereby reducing or preventing binding of the cytokine or functional fragment thereof to its cognate receptor, but upon proteolytic cleavage of the cleavable linker at a target site, the cytokine or functional fragment thereof becomes activated, which renders it capable or more capable of binding to its cognate receptor.

Abstract: The present invention provides, among other things, compositions and methods for prophylaxis and treatment of autoimmune disease. The present invention is based, in part, on the surprising discovery that a human interleukin-2 mutein activates proliferation of regulatory T cells. In one aspect, the present invention provides compositions and methods for proliferation of regulatory T cells. In another aspect, a human interleukin-2 (IL-2) mutein comprising an amino acid sequence that is at least 90% identical to the wild type IL-2 protein is described, wherein the IL-2 mutein has at least one amino acid substitution selected from a group consisting of T111H, T37Y, E15T, M23L, P34F, E68F and E62A.

Abstract: This invention relates to binding molecules that bind specifically to TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) and cadherin-17 (CDH17) and their use in medicine, pharmaceutical compositions comprising the same, and methods of using the same as agents for treatment and/or prevention of cancer.