Therapeutic combinations of immunoconjugates that bind to CD123 (e.g., IMGN632) with BCL-2 inhibitors (e.g., venetoclax), and/or a hypomethylating agent (e.g., azacitidine or decitabine) are provided. Methods of administering the combinations to treat hematological malignancies with clinical efficacy and/or decreased toxicity are also provided. Methods of treating hematological malignances present as minimal residual disease using immunoconjugates that bind to CD123 (e.g., IMGN632) are also provided.

Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

The disclosure provides anti-CD30 antibody-drug conjugates and methods of using the same to increase CD4.sup.+ T-cell lymphocyte count or treat 1-IIV infection. The disclosure also provides articles of manufacture or kits comprising said antibody drug-conjugates that bind to CD30 for increasing CD4.sup.+ T-cell lymphocyte count or treating HIV infection.

Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.

Drug conjugates having formula [D-(X).sub.b-(AA).sub.w-(T).sub.g-(L)-].sub.n-Ab wherein: D is a drug moiety having the following formula (I) or a pharmaceutically acceptable salt or ester thereof, wherein D is covalently attached via a hydroxy group at OR.sub.1, OR.sub.3 or ZH, or a thiol group at ZH to (X).sub.b if any, or (AA).sub.w if any, or to (T).sub.g if any, or (L); that are useful in the treatment of cancer.

##STR00001##

The object of the present invention is to provide a synthetic method for ADC synthesis with controllable regioselectivity and number of drugs introduced, as well as synthetic intermediates and synthetic raw materials for such methods. The object can be solved by a sugar compound having a polyethylene glycol chain, of the following general formula (1).

##STR00001##

wherein each X is independently a single bond, an oxygen atom, —NH—, —COHN—, —COO—, or a group of formula (5) or (6), (wherein R.sup.1 is trivalent branched hydrocarbon group having 1 to 6 carbon atoms, R.sup.2 and R.sup.3 are each independently an alkylene group having 1 to 3 carbon atoms), any one or more of Y1 to Y3 are present and are independently a PEG chain, a substituted PEG chain, or a PEG chain containing an oxygen atom, —NH—, —COHN—, or —COO— in the main chain, a structure of the PEG chain is linear or branched, and the number of branches is 2 to 10 in the case of branched structure, Z is independently a hydroxy group, a methoxy group, an azido group, a tetrazine group which may be optionally substituted, a norbornene group, a trans-cyclooctene group, a dibenzylcyclooctyl group, or a bicyclo[6.1.0]nona-4-yn-9-ylmethyl group, or a cyanobenzothiazole group which may be optionally substituted, wherein at least one of Z is not a hydroxy group or methoxy group, when any of Y1 to Y3 is not present, Z is hydrogen and X is oxygen, when X is the group of formula (5) or (6), Y1 to Y3 are bonded to each of R.sup.2 and R.sup.3 of the branched chains thereof, when the PEG chain is branched structure, Z is bonded to each of branched chains.

The present disclosure provides an antibody, antigen binding fragment thereof, or an antibody conjugate thereof, useful in methods for treatment or diagnosis of conditions characterized by the expression of PTGFRN. The antibodies or antigen binding fragments thereof may also be used in imaging or detecting cells that express PTGFRN.

The present disclosure relates to a modified antibody, or antigen-binding fragment thereof, specific for nectin cell adhesion molecule 4 (nectin-4). The present disclosure also relates to a method of detecting or diagnosing whether a subject has, or is at risk of developing a tumor, or assessing a prognosis of a tumor and a pharmaceutical composition for use in treating, prophylactic treating and/or preventing tumor in a subject afflicted with the tumor.

The present invention relates to antigen-binding molecules, preferably antibodies or antigen-binding fragments thereof, that specifically bind to a GP73, or to an antigenic portion thereof, wherein the antigen-binding molecule binds to an epitope within the extracellular part of GP73 that is internalized into a cell usually subsequent to proteolytic cleavage. The invention further relates to immunoconjugates comprising the antigen-binding molecules, in particular the anti-GP73 antibodies, or antigen-binding fragments thereof. The antigen-binding molecules and immunoconjugates of the invention may be administered alone, as a therapeutic conjugate or in combination with other naked antibodies, or with therapeutic agents, or with other immunoconjugates or as a diagnostic conjugate. The present invention also relates to nucleotide sequences encoding anti GP73 antibodies, and immunoconjugates, vectors and host cells containing the nucleotide sequences, and methods of making anti-GP73-antibodies. The antigen-binding molecules, antibodies and compositions of the invention are useful in diagnostic and therapeutic applications for diseases in which expression of GP73 is altered, in particular in which GP73 is overexpressed, such as cancer.

The invention generally relates to antibodies that bind to human folate receptor 1 and diagnostic assays for folate receptor 1-based therapies. Methods of using the antibodies to monitor therapy are further provided.