The present invention relates to linkers having a group of propiolyl, substituted acryl(acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

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.

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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.

There is disclosed derivatives of amanitin conjugated to a targeting antibody to form an ADC (antibody drug conjugate).

The invention provides methods of using allogeneic cells in therapy by combining allogeneic cell therapy with anti-CD137 antibody drug conjugates (ADCs). Disclosed are methods of treating or preventing a host versus graft (HvG) rejection in a human subject receiving allogeneic cell therapy by administering to the human subject an anti-CD137 ADC.

The invention relates to dosing regimens for antibody drug conjugates, as well as methods of administering said dosing regimens to patients suffering from or at risk of various diseases and conditions such as autoimmune diseases, cancers, and Graft versus Host Disease (GvHD), among others, by administration of an antibody drug conjugate (ADC), capable of binding an antigen expressed by a hematopoietic cell, such as a hematopoietic stem cell, an immune cell or a cancer cell.

The invention provides methods of depleting CD2+ cells in human patients undergoing chimeric antigen receptor (CAR) immunotherapy in order to promote acceptance of CAR expressing immune cells. Anti-CD2 antibody drug conjugates (ADCs) are administered as a conditioning regimen to a human patient receiving autologous or allogeneic CAR expressing immune cells such that the CAR expressing immune cells are accepted by the human patient. Compositions and methods of the invention can be used in combination with CAR therapy to treat a variety of pathologies, including autoimmune diseases and cancer.

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.

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, ligands, 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.

There is disclosed derivatives of amanitin conjugated to a targeting antibody to form an ADC (antibody drug conjugate).

A molecule comprising a saccharide bound via an O-glycosidic bond to a hydroxyl group of a toxic payload molecule is disclosed. An antibody-drug conjugate comprising an antibody covalently bound to a toxic payload molecule, optionally via a linker group, and a saccharide bound via an O-glycosidic bond to a hydroxyl group of the toxic payload molecule is further disclosed.