Chimeric molecules and molecule complexes that include an Fc portion of an antibody and an immunomodulatory portion and uses thereof are contemplated. Typically, the chimeric molecule comprises at least two immune effectors, for example, IL-15 antagonist and PD-L1 binding domain. It is contemplated that a tumor cell or an immune competent cell can be exposed to the chimeric molecule to increase the effectiveness tumor cell lysis via an antibody-dependent cell-mediated cytotoxicity.

The present invention provides tools and methods for the TCR independent activation of T-cells, in particular TCR negative T-cells. In particular, the invention relates to CD3-fusion protein comprising a CDS heterodimer comprising a transmembrane domain, and a CD3 domain. The invention further relates to a nucleic acid molecule encoding such a CD3-fusion protein, a T cell encoding such a CD3-fusion protein as well as said T cell for medical use. Further, the use of the T cell for testing and characterization of exogenous effector molecules is described.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

This disclosure provides multivalent binding molecule comprising a modified J-chain that comprises an immune stimulatory agent. Also provided are polynucleotides encoding the binding molecule or subunits thereof and vectors and host cell comprising said polynucleotides. This disclosure further provides methods for producing and/or using a multivalent binding molecule comprising a modified J-chain that comprises an immune stimulatory agent.

Described herein are engineered anti-IL-2 antibodies with modified amino acid sequences. The engineered antibodies would confer modified receptor binding specificity to an IL-2-anti-IL2 antibody complex, inhibiting the binding of IL-2 to CD25. The engineered anti-IL-2 antibodies would facilitate expansion of subsets of effector immune cells and decrease undesirable effects caused by IL-2. Thus, the engineered anti-IL-2 antibodies would be useful in treating disease such as cancer and infection.

The present invention relates to methods, treatment regimens, uses, kits and therapies for prevention of graft rejection in solid organ transplantation, particularly solid organ xenotransplantation, by administering an anti-CD40 antibody or a combination of an anti-CD40 antibody and an anti-C5 antibody.

The present invention is related to antibodies directed to the antigen CD3 and uses of such antibodies. In particular, the present invention provides fully human monoclonal antibodies directed to CD3. 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, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.

The invention provides means and methods of stimulating activity of a member of the TNF receptor superfamily on a cell. The invention also provides binding molecules such as antibodies that comprises at least two antigen binding sites, wherein a first antigen binding site can bind an extracellular part of CD137 and a second antigen binding site can bind an extracellular part of PD-L1.

Antibodies and antigen binding fragments that bind specifically to TNFRSF25 are provided herein. Methods for using the antibodies and antigen binding fragments to, for example, stimulate proliferation of human T cells (e.g., CD8+ T cells) and to treat cancer patients also are provided.

Provided is a CD96-binding agent, wherein the agent is capable of stimulating activation and/or proliferation of T cells upon binding to CD96. Also provided are isolated nucleic acids and cells that produce the agent and uses thereof.