Although compounds for treating or ameliorating malignant diseases have been proposed, patients had to endure a large burden since many of such compounds could not be orally ingested. Mangiferin has an effect of ameliorating malignant diseases through oral ingestion. However, such effect is minor and realistically it was not easy to ingest mangiferin. Further, in order to develop more effective pharmaceutical agents and the like for treating malignant diseases, it has been considered constantly necessary to obtain new or improved forms of an existing medical agent for inhibiting kinases such as NIK. Compounds represented by formula (1), formula (2), formula (3), formula (4), formula (5), formula (6), formula (7), formula (8), formula (9), formula (10), formula (11), and formula (12) have an effect of ameliorating malignant diseases through oral ingestion, and can exhibit said effect with an amount less than that for mangiferin.

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.

Provided is an GARP protein antibody, and a cell comprising or expressing the GA RP protein antibody. The GARP protein antibody binds to human GARP/human TGF-?1 complex with a K.sub.D value of about 1.0E-12 or less. Also provided are a pharmaceutical combination comprising the GARP protein antibody and an immune checkpoint inhibitor and use thereof.

The present invention concerns antigen binding proteins specifically binding melanoma associated antigen A (MAGE-A) protein-derived antigens. The invention in particular provides antigen binding proteins which specifically bind to the MAGE-A antigenic peptide comprising or consisting of SEQ ID NO: 1 in a complex with a major histocombatibility (MHC) protein. The antigen binding proteins of the invention contain, in particular, the complementary determining regions (CDRs) of novel engineered T cell receptors (TCRs) that specifically bind to said MAGE-A peptide/MHC complex. The antigen binding proteins of the invention are of use for the diagnosis, treatment and prevention of MAGE-A expressing cancerous diseases. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins of the invention.

The present disclosure, among other things, provides low-viscosity, high concentration therapeutic protein agent formulations.

Novel human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases are provided, as well as bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

Provided herein are antibodies, or antigen-binding portions thereof, that specifically bind and inhibit TREM-1 signaling, wherein the antibodies do not bind to one or more Fc?Rs and do not induce the myeloid cells to produce inflammatory cytokines. Also provided are uses of such antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of autoimmune diseases.

Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.

The present invention relates to an antigen-binding molecule comprising a heavy chain variable region comprising a heavy-chain complementarity-determining region 1 (HCDR1) comprising an amino acid sequence represented by Sequence No. 1, an HCDR2 comprising an amino acid sequence represented by Sequence No. 2, and an HCDR3 comprising an amino acid sequence represented by Sequence No. 3; a light-chain variable region comprising a light-chain complementarity-determining region 1 (LCDR1) comprising an amino acid sequence represented by Sequence No. 4, an LCDR2 comprising an amino acid sequence represented by Sequence No. 5, and an LCDR3 comprising an amino acid sequence represented by Sequence No. 6; wherein the antigen-binding molecule is a T cell receptor (TCR); and to a cell line expressing the same.

A novel antibody that can be used as an anti-tumor agent and an anti-tumor agent that comprises, as an active ingredient, a molecule containing such an antibody.