This disclosure provides methods and compositions for detecting Tph cells and/or reducing the number (or frequency) and/or activity of such cells in order to provide therapeutic benefit to a subject having or at risk of developing an autoantibody-associated condition such as an autoantibody-associated autoimmune disease.

Isolated or recombinant monoclonal antibodies that bind to 4-1BB are provided. In son cases, antibodies of the embodiments can be used for the detection, diagnosis and/or therapeutic treatment of human diseases, such as cancer.

The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others. Additional preferred embodiments of the subject invention relate to therapeutic compositions and methods treating or preventing rheumatoid arthritis, especially subcutaneous and intravenous formulations and dosage regimens using IL-6 antagonists according to the invention, as well as methods for preventing or treating GVHD or leukemia relapse in subjects receiving transplanted cells, tissue or organs, use thereof in the treatment or prevention of mucositis, and use thereof to potentiate the cytotoxic, apoptotic, and anti-metastatic or anti-invasive effects of chemotherapeutics and radiation on cancers, especially cancers that have developed a resistance to radiation or chemotherapy, such as an EGFR inhibitor.

The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

The present disclosure provides a method for treating lupus, Sjörgen's syndrome or scleroderma, the method comprising administering to the mammal an immunoglobulin which binds an interleukin 3 receptor α (IL-3Rα) chain and which depletes or at least partly eliminates plasmacytoid dendritic cells (p DCs) and basophils to which it binds.

Compositions and methods for transient immunodepletion of specific subsets of a subject's immune cells are disclosed. The methods generally include administering to the subject an effective amount of a radiolabeled antibody against CD19, CD20, CD33, CD38, CD45RA, CD52, or a combination thereof. The effective amount of the radiolabeled antibody depletes at least 50% of the targeted immune cells, and less than 20% of the subject's stem cells. When used alone, these methods may target lymphomas, leukemias, and myelomas, and/or may additionally allow repopulation of non-autoreactive immune cells in patients with an autoimmune disease. When these methods precede certain cell-based therapies, such as adoptive cell therapy and/or hematopoietic stem cell therapy, the methods are able to enhance the outcome of the cell-based therapies while minimizing adverse effects.

Humanized, chimeric, murine, and human antibody or antigen binding derivatives thereof that bind to an extracellular domain of interleukin-3 (IL-3) receptor α-chain (CD123) anti-CD123 monoclonal antibodies are provided. Nucleic acids encoding the antibody or antigen binding derivative thereof that binds to an extracellular domain of interleukin-3 (IL-3) receptor α-chain (CD123) and expression vectors comprising the nucleic acid are also provided. Bispecific affinity reagents comprising a first binding domain that specifically binds to an extracellular domain of interleukin-3 (IL-3) receptor α-chain (CD123); and a second binding domain that specifically binds to a therapeutic payload and uses thereof are provided. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized, chimeric, or human anti-CD123 monoclonal antibodies; and cell lines that produce these monoclonal antibodies.

The present invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in inducing cell death and/or inhibiting the growth and/or proliferation of cells associated with a solid tumour, wherein the cells express IL1RAP. A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in detecting pathological cells associated with a solid tumour, wherein the cells express IL1RAP. Further provided are pharmacological compositions comprising the agents of the invention and methods of using the same.

The present disclosure reports a C-C chemokine type 2 receptor (CCR2) targeting mediated nanoimmunotherapy to treat cancer, such as pancreatic ductal adenocarcinoma (PDAC). Also disclosed herein is the use of a biodegradable copper nanocluster (CuNC) for enhanced loading of chemotherapeutic drug, such as Gemcitabine (Gem).

This invention provides a method for depleting a subject's hematopoietic stem cells that includes administering to the subject an effective amount of a radiolabeled antibody against CD34, CD117, or CD135, where preferred radiolabels include .sup.131I and .sup.225Ac. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy, where the method includes (i) administering to the subject an amount of the radiolabeled antibody effective to deplete the subject's hematopoietic stem cells, and (ii) after a suitable time period, performing the therapy on the subject to treat the subject's disorder. Finally, this invention provides articles of manufacture for performing the subject methods.