This document provides methods and materials involved in treating cancer. For example, methods and materials for using a BiPE that can include (a) one or more molecules having the ability to bind to a cancer cell (e.g., a human breast cancer cell), (b) an optional linker component, and (c) one or more molecules having the ability to bind to an antigen presenting cell (e.g., a human macrophage) to treat cancer are provided.

A compound which is either A: ##STR00001##
or B: ##STR00002##
and salts and solvates thereof, as well as their conjugates with a cell-binding agent.

Drug conjugates having formula [D-(X).sub.6-(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, ester, solvate, tautomer or stereoisomer thereof, (I) wherein D is covalently attached via a hydroxy or amine group 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.

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 present invention relates to para-amino-benzyl linker compounds useful for linking drug moieties to antibodies, to linker-drug compounds in which said para-amino-benzyl linker compounds are covalently linked to drug moieties, and to antibody-drug conjugates in which said para-amino-benzyl linker compounds are covalently linked to drug wherein said drug is enzymatically cleaved from the conjugate at a particular cell or tissue type targeted by said antibody.

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.

This document provides methods and materials involved in treating cancer. For example, methods and materials for using a BiPE that can include (a) one or more molecules having the ability to bind to a cancer cell (e.g., a human breast cancer cell), (b) an optional linker component, and (c) one or more molecules having the ability to bind to an antigen presenting cell (e.g., a human macrophage) to treat cancer are provided.

The current disclosure provides binding polypeptides (e.g., antibodies), and targeting moiety conjugates thereof, comprising a site-specifically engineered glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

The present disclosure provides conjugates comprising a binding moiety and an immunomodulatory imide compound, e.g., substituted isoindoline compound, wherein the immunomodulatory imide compound is conjugated to a binding moiety via an optional linker. Also provided are compositions comprising the conjugates. The conjugates and compositions are useful for treating a disease or condition, e.g., cancer, in a subject in need thereof.