A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. Engineering T cells with this novel receptor engenders anti -gen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

Described herein are protease-activatable proteins (PABPs), which, when activated, can mediate cytolysis of target cells by effector cells. Also provided are nucleic acids encoding such PABPs and methods of making and using PABPs.

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

The present invention generally relates to antibodies that bind to GPRC5D, including bispecific antigen binding molecules e.g. for activating T cells. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies, and to methods of using them in the treatment of disease.

Disclosed herein are antibody molecules binding specifically to C-KIT, antigen-binding portions thereof and medical uses therefor.

A bispecific antibody, which comprises an antigen-binding portion against human CD3E and/or an antigen-binding portion against human BCMA. Additionally, provided are medical and biological uses of the bispecific antibody.

The present invention relates to a conditioning regimen for the transplant of a cell, tissue or organ, optionally hematopoietic stem / progenitor cells, to a subject. The invention also relates to methods for the induction of hematopoietic chimerism in a subject. The invention also relates to methods for the prevention or treatment of a disease or condition in a subject, in which hematopoietic chimerism is induced in order to improve the benefit to the subject of a subsequent therapy. The subsequent therapy may be a cell, tissue or organ transplant or may a gene therapy administered using genetically modified hematopoietic stem cells/progenitor cells.

The invention relates to a composition comprising a multivalent antibody comprising a first variable domain that binds a first tumor antigen (TA1), a second variable domain that binds a second tumor antigen (TA2) and a third variable domain that binds an immune cell engaging antigen (IEA); and wherein the composition further comprises a second binding molecule that binds TA1 or TA2. The invention also relates to a kit of parts comprising the multivalent antibody and second binding molecule, and to means and methods for the treatment of cancer comprising administering to the subject in need thereof the multivalent antibody and second binding molecule.

The invention relates to the field of immunology and biotechnology, and also to the creation of novel effective high-molecular compounds having therapeutic properties. Variants of amino acid sequences of complementarity-determining regions (CDR) of antigen-binding fragments of a protein molecule specific to human cell CD3 receptors are proposed. The proposed CDR can be used for engineering various antigen-binding molecules, one of the essential function of which is a specific interaction with CD3-bearing cells. Bispecific molecules that specifically bind to human cell CD3 and CD19 receptors were engineered by means of the inclusion of said CDR in the composition of an antibody-like molecule intrinsically binding to the CD19 receptor. The proposed CDR can be used for engineering bispecific therapeutic antibodies that are suitable for creating a drug for treating cancer, in particular for treating haematological diseases associated with B-cell malignancies, such as acute lymphoblastic leukemia and B-cell lymphomas, including the refractory and recurrent forms thereof.

Antibodies, antigen-binding fragments, and conjugates (e.g., antibody-drug conjugates such as those comprising eribulin) thereof that bind to mesothelin are disclosed. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the compositions provided herein.