The present invention provides antibodies and antigen-binding fragments of antibodies that bind to leptin receptor (LEPR), and methods of using the same. According to certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR and antagonize LEPR signaling. In certain embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that bind LEPR in the presence or absence of leptin. In other embodiments, the invention includes antibodies and antigen-binding fragments of antibodies that exhibit partial agonism of LEPR signaling. The antibodies and antigen-binding fragments of the present invention are useful for the treatment of various conditions, including but not limited to congestive heart failure cachexia, pulmonary cachexia and cancer cachexia, autoimmune disorders such as inflammatory bowel disease, lupus erythematosus, multiple sclerosis, psoriasis, cardiovascular diseases, elevated blood pressure, neurodegenerative disorders, depression, cancer such as hepatocellular carcinoma, melanoma, breast cancer, and other diseases and disorders associated with or caused by elevated leptin signaling.

Provided are methods and compositions to target delivery of cells to a tissue lesion, thereby treating the lesion. For example, biotinylated antibodies with affinity to a lesion epitope are administered at the lesion. Reparative cells including avidin and biotin are then administered at the lesion. The reparative cells are targeted to the lesion via avidin-biotin bridges to the antibodies, with additional cells recruited to the lesion via cell-to-cell avidin-biotin bridges. In certain examples, antibody-reparative cell complexes are formed by mixing the biotinylated antibodies with the reparative cells including avidin and biotin. The complexes are then administered at the lesion. In other examples, multivalent antibodies are used to target reparative cells to the lesion, such as by binding an epitope at the lesion and an epitope present on the reparative cell. In other examples, the antibodies are chemically linked to a reparative cell or to a nanosome containing a therapeutic agent.

The present invention relates to a trivalent binding molecule comprising a first polypeptide comprising two binding domains and a second polypeptide comprising a third binding domain. The present invention further relates to the trivalent binding molecule for use in medicine and in particular in the prophylaxis, treatment or diagnosis of a disorder or disease.

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.

The present invention is based, in part, on the discovery of anti-PSGL-1 compositions (e.g., monoclonal antibodies and antigen-binding fragments thereof) that regulate myeloid cell inflammatory phenotypes, such as suppressive myeloid cells, monocytes, macrophages, neutrophils, and/or dendritic cells, including polarization, activation, and/or function, and methods of using such anti-PSGL-1 compositions for therapeutic, diagnostic, prognostic, and screening purposes.

The present invention is based, in part, on the discovery of anti-SIGLEC-9 composition (e.g., monoclonal antibodies and antigen-binding fragments thereof), that regulate myeloid cell inflammatory phenotypes, such as suppressive myeloid cells, monocytes, macrophages, neutrophils, and/or dendritic cells, including polarization, activation, and/or function, and methods of using such anti-SIGLEC-9 compositions for therapeutic, diagnostic, prognostic, and screening purposes.

An isolated monoclonal antibody, or an antigen-binding portion thereof, that specifically binds human TIGIT. A nucleic acid molecule encoding the antibody or antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or antigen-binding portion thereof are also provided. The present disclosure further provides an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody or antigen-binding portion thereof, as well as a treatment method using the antibody or antigen-binding portion thereof.

The present invention discloses that cancer cells secrete succinate into extracellular milieu, which increases macrophage migration and mediates TAM polarization. Furthermore, succinate induces cancer cell EMT, enhances cancer cell migration, and promotes cancer metastasis in murine models. It is indicated in the present invention that serum succinate concentration is elevated in patients with lung cancer when compared to healthy subjects. It implies that during cancer development and progression, cancer cells release a large quantity of succinate into the circulation. As shown in the present invention, serum succinate has a high discriminatory power, it represents a new class of circulating oncometabolite with potential value for predicting NSCLC. Furthermore, as elevation of succinate level in LLC tumor model is accompanied by increased TAMs in the subcutaneous tumors and enhanced cancer metastasis, serum succinate may be a useful therapeutic biomarker for NSCLC treatment. The present invention also provides an anti-succinate antibody that can serve as a cancer therapeutic agent.

The present disclosure relates to anti-CDCP1 antibodies, and antigen binding fragments thereof that specifically bind to the full length and cleaved forms CUB domain-containing protein 1 (CDCP1), and conjugates comprising anti-CDCP1 antibodies and uses thereof for treatment and detection of cancer.

The invention pertains to the field of immunotherapy. The present invention provides a new use of anti-CD127 agent, in particular anti-CD127 antibodies or related compounds for the treatment and/or the prevention of cancer.

The invention relates to a method for treating a patient having a CD127-positive cancer, in particular a CD127-positive leukemia, by administering to the patient a therapeutic dose of an anti-CD127 agent, the anti-CD127 agent having the capability to enhance the Antibody Dependent Cellular Phagocytosis (ADCP) activity of macrophages targeting CD127-positive cancer cells, and that does not have Antibody Dependent Cytotoxic Activity (ADCC), in particular on immune cells, more particularly on T cells.