The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The inventors discovered that viscosity of a protein solution can be estimated by measuring the apparent particle size or apparent molecular weight by a small angle X-ray scattering (SAXS) method or X-ray solution scattering method, which enables measurement of small amounts of samples, and then correlating those measurement results with viscosity of the protein solution.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.

Disclosed is a monoclonal antibody reacting with a glycopeptide, wherein the glycopeptide contains a core fucose moiety and at least 4 contiguous amino acid residues that are located on the C-terminal side of a glycosylated asparagine moiety, and both of the core fucose moiety in the glycopeptide and an amino acid residue that is located apart by at least three amino acid residues from the C-terminal of the glycosylated asparagine moiety in the glycopeptide are epitopes for the antibody.

An objective of the present invention is to provide a polypeptide containing an Fc region having maintained or decreased binding activities towards both allotypes of FcγRIIa, types H and R, and having enhanced FcγRIIb-binding activity in comparison with a parent polypeptide; a pharmaceutical composition containing the polypeptide; an agent for treating or preventing immunological inflammatory diseases that includes the pharmaceutical composition; a production method thereof; and a method for maintaining or decreasing binding activities towards both allotypes of FcγRIIa and enhancing the FcγRIIb-binding activity. Specifically, it is found that a polypeptide containing an antibody Fc region that has an alteration of substituting Pro at position 238 (EU numbering) with Asp or Leu at position 328 (EU numbering) with Glu enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R. It is also found that a polypeptide containing an antibody Fc region that contains an alteration of substituting Pro at position 238 (EU numbering) with Asp and several other alterations, enhances FcγRIIb-binding activity, and maintains or decreases binding activities towards both allotypes of FcγRIIa, types H and R.

An antibody-drug conjugate having a structure represented by formula (I)

##STR00001##

wherein m is 1, 2, 3, or 4 and Ab is an anti-glypican-3 antibody having heavy and light chain CDRs as disclosed herein.

The invention also relates to novel bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD47 and the second is specific for mesothelin (MSLN).

The present invention provides a cell capable of high-yield production of polypeptides and a method for producing the same. The present invention relates to a method for producing a cell capable of high-yield production of a desired polypeptide, wherein a strongly taurine transporter-expressing cell into which DNA encoding the desired polypeptide has been introduced is cultured in the presence of a high concentration of methotrexate and a cell capable of high-yield production of the desired polypeptide is selected from among surviving cells.

The present invention relates to an immune effector cell which expresses a chimeric antigen receptor targeting GPC3 and exogenous IL12. The present invention further provides a pharmaceutical composition containing the immune effector cell and a method for treating tumor, particularly GPC3 positive tumor by using the immune effector cell or the pharmaceutical composition. The immune effector cell in the present invention is effective to an entity tumor cell in vitro, and is outstanding in effect of extinguishing the entity tumor cell in vivo.

Binding proteins, such as antibodies directed to IGF-II with cross-reactivity to IGF-I and uses of such antibodies are described. In particular, fully human monoclonal antibodies directed to the IGF-II with cross-reactivity to IGF-I are disclosed. Also discussed are nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3.