The present disclosure relates to an antigen specific binding domain which binds to RON (Macrophage Stimulating Protein Receptor or Recepteur d'Origine Nantais). The disclosure also extends to chimeric antigen receptors (and a cell expressing the same), antibody molecules (including full length antibodies and fragments thereof, as well as antibody conjugates) containing the antigen binding domains disclosed herein. Also disclosed herein are pharmaceutical compositions comprising the cells, antibody molecules as disclosed herein. The present disclosure also refers to the use of the antigen binding domains, the chimeric antigen receptors, the antibody molecules and the pharmaceutical compositions disclosed herein in therapy, more particularly in treating cancer. Also disclosed herein are radiolabelled antibody conjugates comprising the antigen binding domains as disclosed, and their use in methods of treatment or diagnosis.

Methods of inducing CD8+ T cell infiltration into a tumor in a patient in need thereof comprising administering a radioimmunoconjugate that is capable of binding a target expressed by at least some cells in a 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 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.

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 admistration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.

The present invention is related to a radiolabeled active targeting pharmaceutical composition, including: a bioconjugate and a radionuclide, wherein the bioconjugate includes a biomolecule and a metal nanoparticle, wherein the biomolecule has an affinity for receptors on the surface of a cell membrane and is selected from the group consisting of a peptide and a protein. The present invention further provides a method for evaluating a thermal adjuvant therapy for tumors and a kit thereof. The above-mentioned pharmaceutical composition is applied to evaluate a tumor accumulation time, so as to establish the optimal policy for a radiofrequency- or laser-induced thermal adjuvant therapy for tumors.

Disclosed herein is a radioimmune complex comprising an epidermal growth factor receptor (EGFR)-targeted antibody and a radioactive isotope of rhenium labeled thereon. The EGFR-targeted antibody is cetuximab or panitumumab.

The present disclosure relates to macrocyclic chelates including a macrocyclic chelating moiety of a metal complex thereof, a bifunctional linker, and a therapeutic or targeting moiety. Also disclosed are methods for preparation of the same, and use thereof.

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

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.