The methods and compositions described herein address the need in the art by providing compositions and methods for a therapy with an antibody that is specifically targeted to and/or retained intra- or peri-tumorally, limiting systemic exposure and reducing side-effects. Accordingly, aspects of the disclosure relate to a composition comprising an immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide. An ECM-affinity peptide is one that has affinity for an extracellular matrix protein.

The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137, including antibodies, and molecules comprising epitope-binding fragments thereof The invention is further directed to multispecific binding molecules comprising one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen (“TA”) (e.g, a “CD137×TA Binding Molecule”).

This document provides novel compositions and methods utilizing immunomodulating agents that can stimulate or indirectly augment the immune system, or can have an immunosuppressive effect. TNFR25 agonists disclosed herein have an anti-inflammatory and healing effect. They can be used, e.g., to treat disease caused by asthma and chronic inflammation, such as inflammatory bowel diseases including ulcerative colitis and Crohn's Disease. TNFR25 antagonists disclosed herein can inhibit CD8 T cell-mediated cellular immune responses and can, for example, mitigate organ or tissue rejection following a tissue transplantation. TNFR25 agonists disclosed herein represent biological response modifiers that alter the interaction between the body's cellular immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the cancer when given with tumor vaccines. TNFR25 specific immunotoxins disclosed herein are also capable of increasing the effectiveness of a chemotherapeutic regimen by depleting a cancer patient of naturally occurring immunosuppressive cells.

The invention relates to methods for the treatment of cancer. In particular, the invention relates to methods for the treatment of cancer, comprising administration of a high dose of an antibody capable of binding a human Vγ9Vδ2 T cell receptor.

The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.

The present invention relates to novel human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

The present disclosure provides antibody-drug conjugates comprising (i) antibodies that specifically bind to Mer Tyrosin Kinase (MERTK) (e.g., human MERTK, or both human and mouse MERTK), and (ii) cytotoxic agents conjugated directly to the antibodies or conjugated to the antibodies via linkers, and compositions comprising such antibody-drug conjugates, wherein the antibodies contained in the antibody-drug conjugates agonize MERTK signaling of endothelial cells. The present disclosure also provides methods for treating cancer, by administering an antibody-drug conjugate that comprises (i) an antibody that specifically binds to MERTK and agonizes MERTK signaling of endothelial cells, and (ii) a cytotoxic agent conjugated directly to the antibody or conjugated to the antibody via a linker.

Described herein are, proteins comprising amino acid substitutions in at least one of a first and a second polypeptide chain. Furthermore, is described the uses and methods related to said proteins.

It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

The present disclosure relates to a novel method of treatment of a cancer patient in which the patient is subjected to both an inhibitor of an immune check point molecule, preferably “Programmed Death 1” (PD-1) or its ligand “programmed death ligand 1” (PD-L1), and a Gonadotropin-Releasing Hormone (GnRH, also known as LHRH or FSH-RH) agonist or antagonist.