The present disclosure provides antibody sequences found in antibodies that bind to human CD38. In particular, the present disclosure provides sequences of anti-human CD38 antibodies. Antibodies and antigen-binding portions thereof including such sequences present features compatible with pharmaceutical manufacturing and development can be provided as fully human antibodies (e.g., fully human monoclonal antibodies or antigen-binding fragments) that can be useful for medical methods and compositions, in particular for treating cancer.

The present invention provides antibodies that bind specifically to TrkB and methods of using the same. According to certain embodiments, the antibodies of the invention are agonist antibodies that are neuroprotective, as shown by their effect on enhancing the survival of retinal ganglion cells in vitro. As such, these agonist antibodies may be used to treat diseases or disorders of the eye, such as, but not limited to glaucoma. In addition, other neuronal diseases or disorders may benefit from treatment with these agonist antibodies, including any disease or disorder characterized in part by neuronal damage. In certain embodiments, the invention includes antibodies that bind TrkB and mediate cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies.

Provided herein are compositions and methods for the treatment of a disease, such as cancer, using a chimeric antigen receptor or genetically-modified cells comprising a chimeric antigen receptor having specificity for CD20. The invention provides polynucleotides encoding such chimeric antigen receptors, and genetically-modified cells comprising such chimeric antigen receptors. Also provided are methods for making such genetically-modified cells and pharmaceutical compositions comprising the same. The invention further provides methods for treating a disease (e.g., cancer) in a subject by administering such genetically-modified cells or compositions. The main embodiments concern CARs with an scFv specific for CD20, the hinge and transmembrane domains from CD8, the costimulatory cytoplasmic or signalling domain from co-stimulatory molecules Novell (N1) or Novel6 (N6) and the CD3zeta intracellular signaling domain.

The invention relates to combination therapy involving two or more antibodies, wherein the Fc regions of the two antibodies have been modified such that hetero-oligomerization between the antibodies is strongly favored over self-oligomerization when antibodies are bound to their corresponding target antigens and such that hetero-oligomerization-independent effector functions of one or both antibodies are eliminated or strongly reduced. The invention also relates to antibodies, compositions, and kits suitable for use in the combination therapy of the invention.

The disclosure provides a method of treating unresectable or metastatic melanoma in a human patient with a lymphocyte activation gene-3 (LAG-3) antagonist. In some aspects, the method includes a combination of the LAG-3 antagonist with a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor. In some aspects, the method includes one or more additional therapeutic agents and/or anti-cancer therapies.

The present disclosure relates generally to compositions and methods useful for the production of engineered antibodies having (i) multiple antigen-binding specificities and (ii) Fc regions that have been modified to promote heterodimer formation between heavy chains from antibodies with different specificities. Also provided are recombinant cells, recombinant nucleic acids encoding such engineered antibodies, as well as pharmaceutical compositions containing same.

Provided is an anti-PD-L1 antigen binding protein, capable of binding to primate-derived PD-L1 with a KD value of 1×10.sup.−8 M or less. The antigen binding protein can block the binding of PD-1 and CD80 to PD-L1, stimulate the secretion of cytokines in immune cells, and can inhibit tumor growth and/or tumor cell proliferation. Also provided is a fusion protein, comprising human TGFBRII or a fragment thereof and the antigen binding protein. Also provided is an application of the antigen binding protein and/or the fusion protein in the prevention and treatment of tumors or cancers.

The present invention relates to novel tri-specific binding molecules. The invention also relates to nucleic acids encoding such binding molecules; to methods for preparing such binding molecules; to host cells expressing or capable of expressing such binding molecules; to compositions comprising such binding molecules; and to uses of such binding molecules or such compositions, in particular for therapeutic purposes in the field of cancer diseases.

The present disclosure provides novel antibodies and fragments thereof targeting IL-1RAcP. Use of IL-1RAcP inhibitors are also provided herein.

Antibodies and antibody-drug conjugates that selectively bind to a membrane-associated extracellular portion of a cleaved amphiregulin precursor protein; methods of using the antibodies and antibody-drug conjugates to detect and inhibit the growth of neoplastic cells; pharmaceutical compositions containing the antibodies and/or antibody-drug conjugates as the active ingredient(s); kits containing the antibodies and/or antibody-drug conjugates.