This invention provides a method for treating a subject afflicted with cancer, comprising administering to the subject (i) a BCL-2 inhibitor in conjunction with (ii) an alpha-emitting isotope-labeled agent that targets cancer cells in the subject, wherein the amounts of the BCL-2 inhibitor and labeled agent, when administered in conjunction with one another, are therapeutically effective. This invention also provides a method for inducing the death of a cancer cell, comprising contacting the cell with (i) a BCL-2 inhibitor in conjunction with (ii) an alpha-emitting isotope-labeled agent that targets the cancer cell, wherein the amounts of BCL-2 inhibitor and labeled agent, when concurrently contacted with the cell, are effective to induce the cell's death.

Methods and compositions for treating, diagnosing and staging cancers, in particular overexpressing the Human Epidermal growth factor Receptor 2 protein (HER2+) given rise to in breast, gastric, gastroesophageal, ovarian, pancreatic cancer and brain tumors, which may be metastatic to the brain or other site. More specifically, the invention provides for Targeted Radionuclide Therapy (TRNT) with a compound of the invention having a peptide that targets the HER2+ cells, a second component for combining metals into complexes through a ring structure (DOTA), and a third radioisotope component, Lu-177 and Ga-68, in which embodiments further include a companion diagnostic, and in which embodiments further include anti-integrin precision medicines for cancers expressing αvβ3 and αvβ5 integrins, HER2+, vascular endothelial growth factor, vitronectin, fibronectin, tenascin, reelin, kindlin and talin. TRNT may be administered alone or in combination with standard-of-care; an immunooncologic and/or chemotherapeutic, adjuvantly or neoadjuvantly.

The present invention relates to the use of an inhibitor of HER-3 for the treatment of a hyperproliferative disease in combination with radiation treatment.

The disclosure relates to the use of .sup.177Lu-lilotomab satetraxetan in the treatment of Non-Hodgkin lymphoma. Aspects included are specific administration patterns, with specific concentrations, pre-treatments and predosing.

A chelating agent having the general formula (I) is provided (I) Metal chelates and constructs for carrying out targeted radionuclide therapy incorporating such chelating agents are provided. Methods of making and using the chelating agent, metal chelates and constructs for carrying out targeted radionuclide therapy, as well as diagnostic and therapeutic methods using such constructs, are provided.

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Combination therapies comprising administering radioimmunoconjugates and one or more checkpoint inhibitors.

Among the various aspects of the present disclosure is the provision of compositions of isotope-ligand complexes, methods of use thereof, and methods of chelating isotopes. The present disclosure also provides for methods for modulating ion channel transportation of radiopharmaceuticals. For example, the inhibition of radiopharmaceutical transport comprises administering an ion channel transport modulating or inhibiting agent (e.g., a calcium channel inhibitor) in an amount effective to inhibit gastrointestinal uptake.

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The present disclosure provides an isolated, engineered or non-naturally occurring protein comprising an antibody light chain variable domain (V.sub.L) which may comprise at least one negatively charged amino acid positioned between residues 49 to 56 according to the numbering system of Kabat, the protein capable of binding specifically to an antigen.

The present invention provides antibody polypeptides with binding specificity for prostate specific antigen (PSA), wherein the antibody polypeptide comprises (a) a heavy chain variable region comprising the amino acid sequences of SEQ ID NO:1 and SEQ ID NO:2 and SEQ ID NO:3 and/or (b) a light chain variable region comprising the amino acid sequences of SEQ ID NO:4 and SEQ ID NO:5 and SEQ ID NO:6, and wherein the heavy chain variable region and light chain variable region comprise framework amino acid sequences from one or more human antibodies. The invention further provides use of said antibody polypeptides in the diagnosis and treatment of prostate cancer.

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