The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.

##STR00001##

wherein “” is an optional bond; X, Y, Z.sub.1, and Z.sub.2 are a functional group; m.sub.1 and n are a integer; L.sub.1 and L.sub.2 are a linker.

Provided herein are antibody conjugates with binding specificity for CD74 and compositions comprising the antibody conjugates, including pharmaceutical compositions, methods of producing the conjugates, and methods of using the conjugates and compositions for therapy.

The invention relates to novel methods for synthesizing amanitin derivatives having a hydroxy group attached to the central tryptophan moiety. The invention furthermore relates to novel amanitin derivatives having a hydroxy group attached to position 4′, 5′ or 7′ of the central tryptophan moiety, novel conjugates of such amanitin derivatives, and pharmaceutical compositions comprising such conjugates.

The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell-, particularly B-cell and/or lymphoma associated diseases and/or malignancies.

The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.

Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.

The invention provides anti-TIM3 antibodies and methods of using the same.

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein 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.

This disclosure provides ASCT2-binding molecules, e.g., anti-ASCT2 antibodies, and antigen-binding fragments thereof. In certain aspects, the ASCT2-binding molecules are conjugated to cytotoxic drugs, e.g., ASCT2 antibody-drug conjugates (ADCs). In certain aspects, the anti-ASCT2 antibodies and fragments thereof can be hybridoma-derived murine monoclonal antibodies, and humanized versions thereof. In certain aspects, the ASCT2-binding molecules bind specifically to cells expressing ASCT2, and in some instances, are internalized into the cells. In addition, this disclosure provides compositions and methods for diagnosing and treating diseases or disorders characterized by ASCT2 overexpression, e.g., certain types of cancer. In a particular embodiment, the disclosure provides methods for treating cancer using ASCT2 ADCs.