The present application relates to antibodies which bind specifically to chelated radionuclides, including bispecific antibodies, It further relates to the use of such bispecific antibodies in applications such as radioimmunoimaging and radioimmunotherapy. It additionally relates to clearing agents and useful in such methods.

The present invention provides a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand and the ion of an alpha-emitting thorium radionuclide. The invention additionally provides therapeutic methods employing such complexes, methods of their production and use, and kits and pharmaceutical compositions comprising such complexes.

Described herein are compositions and methods of use of antibody-drug conjugates (ADCs) comprising an anti-Trop-2 antibody or antigen-binding fragment thereof, conjugated to one or more cytotoxic drugs. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. More preferably, the antibody is humanized. Preferably the drug is SN-38, pro-2-pyrrolinodoxorubicin, paclitaxel, calichemicin, DM1, DM3, DM4, MMAE, MMAD or MMAF. The compositions and methods are of use to treat Trop-2 expressing cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer. Preferably, the cancer is one that is resistant to one or more standard cancer therapies. More preferably, the anti-Trop-2 antibody binds to Trop-2 expressed on normal cells, but administration of the anti-Trop-2 ADC to human cancer patients at a therapeutically effective dosage produces only limited toxicity.

Cysteine engineered antibodies comprising a free cysteine amino acid in the heavy chain or light chain are prepared by mutagenizing a nucleic acid sequence of a parent antibody and replacing one or more amino acid residues by cysteine to encode the cysteine engineered antibody; expressing the cysteine engineered antibody; and isolating the cysteine engineered antibody. Certain highly reactive cysteine engineered antibodies were identified by the PHESELECTOR assay. Isolated cysteine engineered antibodies may be covalently attached to a capture label, a detection label, a drug moiety, or a solid support.

The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following:

##STR00001## or a pharmaceutically acceptable salt thereof,

##STR00002## or a pharmaceutically acceptable salt thereof,

##STR00003## or a pharmaceutically acceptable salt thereof,
wherein M.sup.1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

The invention provides anti-B7-H4 antibodies and immunoconjugates and methods of using the same.

Provided are an anti-Her2 nanobody and a coding sequence and the use thereof. In particular, provided is a nanobody combating human epidermal growth factor receptor-2 (Her2/ERBB2). Disclosed are the nanobody and the a gene sequence encoding the nanobody, a corresponding expression vector and a host cell capable of expressing the nanobody, and a method for producing the nanobody of the present invention and the related use thereof. The present invention may also provide an immunoconjugate of the nanobody and the use thereof, especially the use in the diagnosis and treatment of Her2 positive tumor.

The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising; a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a methyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting moiety targeting HER2; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope.
A method of treatment of a neoplastic or hyperplastic disease comprising administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided

Provided are compositions and methods for treating a solid cancer such as a HER3-positive tumor in a subject by administering an effective amount of a HER3-targeting agent labeled with a radionuclide such as .sup.225Ac, .sup.177Lu, .sup.131I, .sup.90Y, .sup.213Bi, .sup.211At, .sup.213Bi, .sup.227Th, or .sup.212Pb, alone or in combination with other therapeutic agents or modalities. The effective amount of the radiolabeled HER3-targeting agent may be a maximum tolerate dose administered in a single bolus or in fractionated doses that together equal the maximum tolerated dose.

The present invention relates to combinations of at least two components, component A and component B, component A being a PD-1/PD-L1 inhibitor, and component B being a targeted thorium conjugate. Another aspect of the present invention relates to the use of such combinations as described herein for the preparation of a medicament for the treatment or prophylaxis of a disease, particularly for the treatment of breast and prostate cancer.