A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.

A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.

Provided is a mutant of an antibody or fragment thereof, characterized in that the antibody or fragment thereof contains a light-chain constant region, and according to the Kabat numbering system, the amino acid at position 166 is mutated to cysteine.

The present invention relates to an immune cell that are engineered to overexpress cell signaling pathway modulator(s) and a use thereof. As a specific example, an immune cell expressing a fusion protein comprising a chimeric antigen receptor and a cell signaling pathway modulator(s) performs an immune response by selecting a target cancer cell by a chimeric antigen receptor expressed on a cell membrane. In this case, the cell signaling pathway modulator is overexpressed in the cytoplasm, thereby being capable of regulating the activity of an immune cell. Therefore, the fusion protein comprising a chimeric antigen receptor and cell signaling pathway modulator(s), and the immune cell engineered to overexpress the cell signaling pathway modulator(s) of the present invention can be usefully used in the treatment of cancer.

Described herein are methods and compositions for treating asthma or an allergic disease. Aspects of the invention relate to administering to a subject an agent that targets the Wnt or Hippo Signaling pathway, or Growth-differentiation factor 15 (GDF15), either alone or in combination. In certain embodiments, the subject is further administered a Notch4 inhibitor.

Described herein are methods and compositions for treating asthma or an allergic disease. Aspects of the invention relate to administering to a subject an agent that targets the Wnt or Hippo Signaling pathway, or Growth-differentiation factor 15 (GDF15), either alone or in combination. In certain embodiments, the subject is further administered a Notch4 inhibitor.

The invention relates to compounds of general structure (1): Q-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L.sup.1, L.sup.2, L.sup.3 and L.sup.4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21): ##STR00001##
wherein R.sup.12═C.sub.1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L.sup.4).sub.q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L.sup.6)-Z-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D].sub.xx (2), wherein Z is a connecting group that is formed in a click reaction, L.sup.6 is a linker that links Z to Pr and Pr is a (glyco)protein.

Provided are a tumor antigen polypeptide having the amino acid sequence as shown in SEQ ID NO: 2 or a variant thereof; a nucleic acid encoding the same; a nucleic acid construct, an expression vector, and a host cell containing the encoding nucleic acid; and an antigen presenting cell presenting the tumor antigen polypeptide on the cell surface and an immune effector cell thereof. Also provided is the use of the polypeptide, nucleic acid, antigen presenting cell or immune effector cell in the diagnosis, prevention and treatment of cancers.

A method for producing a protein is provided. An objective protein is produced by culturing in a culture medium Talaromyces cellulolyticus having an objective protein-producing ability, which has been modified so that the activity of a Pep4 protein is reduced.

The invention provides a method for treating or preventing brain metastases comprising the step of administering to a patient in need a composition comprising a therapeutically effective amount of LCN2 Inhibitor, an agent that interferes in systemic LCN2 signaling pathways, or an agent that reduces LCN2 expression or any combination thereof.