The present disclosure provides multispecific binding molecules that specifically bind to BCMA, a component of a human T-cell receptor complex and either CD2 or a tumor associated antigen, conjugates comprising the multispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates The disclosure further provides methods of using the multispecific binding molecules to treat disease and disorders associated with expression of BCMA. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.

This invention relates to humanized antibodies that selectively bind the 31.1 epitope on the A33 protein differentially expressed in cancers including, lung cancer, ovarian cancer, pancreas cancer, breast cancer, and colon cancer, and diagnostic and therapeutic usages.

Multifunctional molecules that include i) an antigen binding domain that binds to CD33; and one or both of: an immune cell engager (e.g., chosen from a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager) or a cytokine molecule. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

The present invention provides agents comprising or consisting of a binding moiety with specificity for Signaling Lymphocytic Activating Molecule Family Member 6 (SLAMF6) for use in inducing cell death and/or inhibiting the growth and/or proliferation of pathological stem cells and/or progenitor cells associated with a neoplastic hematologic disorder, wherein the cells express SLAMF6 and/or modulating their interactions with immune cells that may also express SLAMF6. A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for SLAMF6 for use in detecting pathological stem cells, progenitor cells and/or immune cells associated with a neoplastic hematologic disorder, wherein the cells express SLAMF6. Further provided are pharmacological compositions comprising the agents of the invention and methods of using the same.

The present disclosure provides methods of treating a subject having a proliferative disease or an autoimmune disorder with a combination of (a) a first multispecific binding molecule (MBM) that binds specifically to (i) human CD2 and (ii) a human tumor-associated antigen and/or a human tumor microenvironment antigen, and (b) a second multispecific binding molecule that binds specifically to (i) a component of a human T-cell receptor (TCR) complex or a secondary T-cell signaling molecule and (ii) a human tumor-associated antigen and/or human tumor microenvironment antigen. The disclosure further provides MBMs and combinations of MBMs that can be used in the methods of the disclosure.

The present invention relates to a blocking-reagent for use in reducing unspecific T cell activation in T cell engaging therapies. The present invention further relates to pharmaceutical kit of parts and an in vitro method for evaluating unspecific T cell activation.

The invention relates to COnditional Bispecific Redirected Activation constructs, or COBRAs, that are administered in an active pro-drug format. Upon exposure to tumor proteases, the constructs are cleaved and activated, such that they can bind both tumor target antigens (TTAs) as well as CD3, thus recruiting T cells expressing CD3 to the tumor, resulting in treatment. In some embodiments, the tumor target antigen is B7H3.

Novel synthetic biology-based ADCC technologies are provided that enhance or enable ADCC responses, for example, through a rationally-designed soluble universal ADCC enhancer protein (SUAEP) where a high-affinity CD3-binding domain is fused to a high-affinity Fc-binding domain. The SUAEP technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.

Compositions and methods for treating MM are provided herein.

The present invention includes compositions and methods for treating T cell lymphomas and leukemias. In certain aspects, the compositions and methods include CAR T cells targeting CD2, CD5, or CD7 and modified cells wherein CD2, CD5, or CD7 has been knocked-out.