The invention provides, inter alia, methods of treating a disorder characterized by pathological activity of CD30+ cells, such as in certain solid, hematological and lymphoid cancers, in a non-adult human subject by administering an effective amount of an anti-CD30 ADC (antibody drug conjugate), such as, brentuximab vedotin, to the subject. The invention also provides corresponding kits and articles of manufacture suitable for performing the methods provided by the invention.

Amatoxins, as well as antibody-drug conjugates (ADCs) comprising an amatoxin are provided, as well as compositions and methods of using the same. The compositions and methods provided herein can be used for cancer therapy. They can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure. Methods and compositions for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, as well as prevention of graft-versus-host-disease (GVHD), are provided.

The present invention relates to receptor tyrosine kinase-like orphan receptor 1 (ROR1) specific antigen binding molecules and associated fusion proteins and conjugates. In a further aspect, the present invention relates to conjugated immunoglobulin-like shark variable novel antigen receptors (VNARs).

The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

The present invention relates to an anthracycline (PNU) derivative conjugate comprising a derivative of the anthracycline PNU-159682 having the formula (i) or formula (ii) which further comprises a linker structure X-L1-L2-L3-Y.

Methods of administering immunoconjugates that bind to CD37 (e.g., IMGN529) in combination with antibodies that bind to CD20 are provided. The methods comprise administering an anti-CD37 immunoconjugate (e.g., IMGN529) and an anti-CD20 antibody to a person in need thereof, for example, a cancer patient.

This application discloses compositions and methods of treating follicular lymphoma using CCR7 antibody drug conjugates. Also disclosed herein are methods of treating cancer in a subject in need thereof, comprising administering to said subject an antibody drug conjugate, wherein the cancer expresses CCR7, wherein the antibody drug conjugate is administered to said subject at about 0.1 mg/kg to about 10 mg/kg.

The present invention relates to the treatment of cutaneous T-cell lymphomas (CTCL) and T.sub.FH derived lymphomas. In this study, the inventors showed the expression of ICOS by tumor cells in the skin of patients with MF and SS (CTCL) at different stages of the disease, and in the blood of patients with SS. The idea was thus to kill these tumor cells using ADC-antibodies specifics to ICOS. Thanks to cell lines murine xenograft models and Patient Derived Xenografts (PDXs), they showed the efficacy of such anti-ICOS ADCs on T.sub.FH-derived lymphomas, such as CTCL and AITL. Thus, the present invention relates to an anti-ICOS antibody for use in the treatment of a cutaneous T-cell lymphomas (CTCL) and/or a TFH derived lymphoma in a subject in need thereof.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38.sup.30 cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic rnyelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38, Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

A composition comprising a cell or a population thereof, wherein the cell comprises a polynucleotide encoding an antibody or a fragment thereof that binds CD269 (BCMA), wherein the binding to CD269 (BCMA) disrupts the interaction between CD269 and its native ligands (BAFF and APRIL). Also disclosed is treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.