The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) 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.

The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (I), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates: ##STR00001##

The present disclosure relates to combination therapies with antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs. Also provided are methods of using the combinations with antibody conjugates and compositions thereof, such as in therapeutic and diagnostic methods.

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

The invention relates to conjugates comprising amatoxins and antibodies, in particular amatoxins linked to antibodies comprising specific cysteine residues.

Provided herein are methods of treating a patient having a cancer that exhibits (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) expression level. The methods comprise administering a therapeutically effective amount of a POLR2A inhibitor (e.g., a nucleic acid that inhibits the expression of a POLR2A protein, an amatoxin, alpha-amanitin, or alpha-amanitin conjugated to a cell targeting moiety, such as an EpCAM antibody) to a patient having or determined to have (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) level.

Disclosed are a recombinant fusion antibody, and an antibody-drug conjugate and use thereof. The recombinant fusion antibody includes an antibody, at least one lysosome-targeting peptide, and at least one linker peptide, wherein the antibody is fused with the lysosome-targeting peptide to form the recombinant fusion antibody via the linker peptide; wherein the lysosome-targeting peptide is at least one selected from the group consisting of a lysosome-sorting signal peptide from a Golgi-localized, -adaptin ear-containing, ARF-binding protein (GGA), a lysosome-sorting signal peptide from a mannose 6-phosphate receptor (MPR), a lysosome-sorting signal peptide from a lysosome-associated membrane protein (LAMP), and a variant; wherein the variant is a peptide with one or more amino acids substituted, deleted, and/or added when aligned with the lysosome-sorting signal peptide from a GGA, a MPR or a LAMP. Compared with the original antibody, the internalization and lysosomal trafficking ability of the recombinant fusion antibody are significantly improved.

The present invention provides antibody drug conjugates, wherein an antibody or antibody fragment that specifically binds to human cKIT is linked to a drug moiety, optionally through a linker. The present invention further provides pharmaceutical compositions comprising the antibody drug conjugates; and methods of making and using such pharmaceutical compositions for ablating hematopoietic stem cells in a patient in need thereof.

Provided herein are single-domain antigen binding molecules able to bind uPAR. Also provided herein are methods of treating cancer, fibrotic disease, or diseases related to senescent cell phenotypes in which uPAR is expressed.

The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications.