The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.

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.

Isolated polypeptides having a heavy chain variable region and/or light chain variable region that specifically binds to Nectin-4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to Nectin-4 protein. Pharmaceutical compositions and kits comprising the polypeptide and antibodies and antibody fragments containing the polypeptide are also provided.

The present invention relates to a process for preparing antibody-drug conjugates and to antibody-drug conjugates wherein therapeutic moieties are conjugated to one or more engineered cysteines as well as to one or more reduced interchain cysteines via a cleavable or non-cleavable linker.

The invention provides compositions comprising a single protein having one or more molecules of a pharmaceutical agent tightly bound therein. The compositions are useful to decrease the toxicity and/or to widen the therapeutic window of the pharmaceutical agent. The invention also provides methods for preparing such a composition.

The invention relates to compounds of general structure (1): Q-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L.sup.1, L.sup.2, L.sup.3 and L.sup.4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21): ##STR00001##
wherein R.sup.12═C.sub.1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L.sup.4).sub.q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L.sup.6)-Z-(L.sup.1).sub.n-(L.sup.2).sub.o-(L.sup.3).sub.p-(L.sup.4).sub.q-D].sub.xx (2), wherein Z is a connecting group that is formed in a click reaction, L.sup.6 is a linker that links Z to Pr and Pr is a (glyco)protein.

A method for producing exosomes in a large-scale by using a cyclic tensile bioreactor to stimulate cells to release exosomes. In addition, the exosome having an anti-HLA-G protein specific for cancer is used as a delivery vehicle to deliver therapeutic agents for treating cancer.

The present disclosure provides, inter alia, multi-drug Antibody Drug Conjugates (MD-ADCs) and Linking Assembly (LA) Units, that are constructed in a site-specific matter via ‘orthogonal’ deprotection and drug loading. Also provided are, Protected Linking Assembly Units, which allow for ‘orthogonal’ deprotection and construction of MD-ADCs and LA Units of the present disclosure.

The present invention relates to a cleavable linker platform. In particular, the invention relates to construction of an enzyme cleavable linker platform conjugated to a drug or a diagnostically relevant compound, a biomolecule, and an enzyme cleavable group, for which cleavage of the enzyme cleavable group leads to release of the drug or diagnostically relevant compound.

This disclosure relates generally to compositions of carbon dots, doxorubicin, and transferrin and methods for use of the same in the treatment of DLBCL tumors.