The invention relates to bispecific antibodies comprising a first antigen binding domain that specifically binds to PD1 and a second antigen binding domain that specifically binds to LAG3. The invention further relates to methods of producing these molecules and to methods of using the same.

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.

The present disclosure provides methods and compositions that include a polynucleotide that includes nucleic acids that encode an anti-idiotype polypeptide, as well as polypeptides that are encoded by the same, and cells that include and express the polypeptide. Disclosed methods include methods that utilize the anti-idiotype polypeptides as safety switches when they are used in combination with antibodies, include approved biologic antibodies, that include the recognized idiotype. Certain embodiments include anti-idiotype polypeptides and nucleotides encoding the same, that include an internal domain. This internal domain in some embodiments has functional domains that can induce proliferation or cell death upon binding of the anti-idiotype polypeptide by its target antibody.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

The instant invention provides soluble fusion protein complexes and IL-15 variants that have therapeutic and diagnostic use, and methods for making the proteins. The instant invention additionally provides methods of stimulating or suppressing immune responses in a mammal using the fusion protein complexes and IL-15 variants of the invention.

Multispecific molecules that include i) a tumor-targeting moiety; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule; and/or (iv) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

The present invention provides a combination therapy for treating a tumor in a subject. The combination comprises two elements. The first is a polypeptide construct comprising an attenuated Type I interferon (IFN) linked to an antibody which binds to a cell surface-associated antigen expressed on the tumour cell and comprising a functional Fc region. The second is a CD47 antagonist which inhibits the interaction CD47 with the SIRPα receptor.

Provided is a technique for highly expressing a target protein in a plant cell by using a glycosylation domain, a recombinant vector comprising a gene encoding a fusion protein of a glycosylation domain and a target protein, a recombinant cell, a transformed plant, and a method of producing a target protein using these.