The present invention relates to a humanized DR4 antibody gene having apoptosis-inducing activity, and a dual-acting chimeric antigen receptor T cell or natural killer cell therapeutic agent, a secretory DR4 scFv antibody recombinant protein synthesized by using a humanized DR4 scFv antibody gene (humanized anti-DR4 scFv) may be used as an anticancer drug specifically targeting DR4 by binding to DR4 expressed on surface of the cancer cells to induce apoptosis of the cancer cells. In addition, the chimeric antigen receptor (CAR) using the humanized DR4 scFv antibody gene is predicted to have a strong anticancer immune effect as a dual-acting cell therapeutic agent, which is capable of simultaneously inducing apoptosis in cancer cells by DR4 and exhibiting a cytotoxic effect for cytotoxic T lymphocytes or natural killer cells by binding to DR4 expressed on the surface of cancer cells, as a DR4-specific CAR-T cell or CAR-NK cell therapeutic agent.

Provided herein are methods of treating cancer using agonistic antibodies that specifically bind to immunostimulatory receptors, wherein the antibodies are administered in an amount and/or frequency sufficient to achieve and/or maintain a receptor occupancy of less than about 80%, for example, a receptor occupancy of about 20% to about 80%. Also provided are methods of determining human doses for such agonistic antibodies, and methods for monitoring receptor occupancy of the agonistic antibodies in order to maintain effective antibody levels in, e.g., human patients. Also provided are methods of measuring soluble OX40 in a subject. Also provided are methods of treating cancer, comprising administering to the subject an effective amount of each of an anti-OX40 antibody and an anti-PD-1 antibody.

The present invention relates to antibodies that specifically bind CD3. The present invention relates to antibodies that specifically bind PSMA. The present invention relates to antibodies that specifically bind CD3 and PSMA. The present invention relates to antibodies that specifically bind IL1RAP. The present invention relates to antibodies that specifically bind CD33. The present invention relates to antibodies that specifically bind CD3 and IL1RAP. The present invention relates to antibodies that specifically bind CD3 and CD33. The present invention relates to antibodies that specifically bind TMEFF2. The present invention relates to antibodies that specifically bind CD3 and TMEFF2. The present invention relates to fragments of the antibodies, polynucleotides encoding the antibodies or fragments thereof, and methods of making and using the same.

Provided are agonist anti-ENG coreceptor-specific antibodies and agonist anti-ENG coreceptor-binding fragments thereof, including antibodies that bind to the BMP9-binding region within an ectodomain of an ENG coreceptor, as well as methods of use employing such antibodies and/or fragments in treating diseases such as HHT and PAH.

Provided herein are VHH-containing polypeptides that bind OX40. In some embodiments, VHH-containing polypeptides that bind and agonize OX40 are provided. Uses of the VHH-containing polypeptides are also provided.

Certain embodiments described herein provide a method for treating dysregulated lipid metabolism and/or inflammation in a mammal in need thereof, comprising administering to the mammal an effective amount of an agonist anti-triggering receptor expressed on myeloid cells 2 (TREM2) antibody.

Embodiments of the present invention relate to compositions and methods for activating canine OX40 to treat a condition in dogs. In certain embodiments, the condition can be cancer or an immunosuppressed condition in dogs and OX40 activation treats, ameliorates or prevents onset or progression of the condition. In other embodiments, compositions disclosed herein generally relate to compositions including, but not limited to, activating antibodies having specific affinity for OX40 for inducing activity of canine OX40. In other embodiments, compositions disclosed herein can be used for treating certain cancers or an immunosuppressed condition to treat the cancer or alleviate immunosuppression in dogs. In certain embodiments, other immune activators can be administered in combination with OX40 activating antibodies such as Toll-Like Receptor (TLR) ligands alone or in combination with other non-specific immunostimulant agents.

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind a TREM1 protein, e.g., a mammalian TREM1 or human TREM1, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

The present disclosure provides binding proteins, such as antibodies and binding fragments thereof, that bind beta klotho, including human beta klotho, and methods of their use, including in the treatment of nonalcoholic steatohepatitis. The present disclosure also provides exemplary specific sequences of complementarity determining regions, variable regions, heavy chains, and light chains of the antibodies and/or binding fragments thereof.

The invention discloses that ER-negative breast cancers can be converted into ER positive breast cancers, such as to a breast cancer of luminal-like phenotype by treatment with anti-PDGF-CC antibodies. ER-positive breast cancers, including luminal-like breast cancers can be treated with anti-estrogen treatment. On this basis the invention discloses that surprisingly, ER-negative breast cancers can be treated with anti-estrogen treatment, if the treatment is combined with treatment with anti-PDGF-CC antibodies. Said treatment may for example be an adjuvant treatment, for example a treatment aiming at reducing the risk of relapse of a breast cancer after removal of the primary tumor by surgery.