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.

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 such as VEGF or VEGFR inhibitors. The effective amount of the radiolabeled HER3-targeting agent may be a maximum tolerated dose administered in a single bolus or in fractionated doses that together equal the maximum tolerated dose.

The present invention relates to conjugates including a residualizing linker, methods for their production, and uses thereof.

Provided herein are antigen-binding protein constructs capable of specifically binding MET or an epitope of MET presented on surface of a target mammalian cell, wherein said antigen binding is pH-dependent. Provided are also uses of said antigen-binding protein constructs.

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

This invention provides a method for depleting a subject's hematopoietic stem cells that includes administering to the subject an effective amount of a radiolabeled antibody against CD34, CD117, or CD135, where preferred radiolabels include .sup.131I and .sup.225Ac. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy, where the method includes (i) administering to the subject an amount of the radiolabeled antibody effective to deplete the subject's hematopoietic stem cells, and (ii) after a suitable time period, performing the therapy on the subject to treat the subject's disorder. Finally, this invention provides articles of manufacture for performing the subject methods.

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

Combination therapies comprising administering radioimmunoconjugates and DNA damage response inhibitors.

The present invention relates to anti-cKIT antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of 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 C.sub.1-C.sub.3alkyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting peptide or protein comprising at least one amine moiety by means of at least one amide-coupling reagent whereby to generate a tissue-targeting chelator; 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.