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 compositions useful in such methods. The chelated radionuclides may be a DOTAM-lead (Pb) chelate.

Compositions and methods useful for the treatment of hemoglobinopathies and hematological diseases are disclosed herein. The compositions include an actinium-225 labeled anti-CD45 antibody (BC8) formulated as a single patient dose that is wholly deliverable to a patient in a single dose. The actinium-225 labeled anti-CD45 may be administered alone or in combination with additional therapeutic agents, such as other immunotherapeutics or a radiosensitizing agent, or additional therapeutic interventions, such as bone marrow transplant or adoptive cell therapies.

A targeted radiopharmaceutical comprising a targeting species chemically-bonded to a PCTA-chelated Q.sup.+3 trivalent radioactive ion of Formula I

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is disclosed. Six of R.sup.1 through R.sup.7 are H and the seventh is a reacted functionality, Z, that forms the chemical bond with the targeting species, T. “g” is a number whose average value is 1 to about 12. X.sup.1, X.sup.2, and X.sup.3, are substituent groups that can coordinate to the Q.sup.+3 ion and/or help neutralize the ionic charge. Anion Y.sup.− is optionally present to balance the ionic charge. A pharmaceutical composition comprising a theranostic effective amount of a targeted radiopharmaceutical of Formula I in a pharmaceutically acceptable diluent is also contemplated, as are a method for treating and/or diagnosing a mammalian host having a disease, disorder or condition characterized by undesired angiogenesis, tumor growth and/or tumor metastasis.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

The present disclosure provides methods for site-selectively crosslinking payloads to antibodies and other proteins. This can be accomplished using traceless affinity labels designed to label target proteins with bio-orthogonally reactive entities (ORE) using the compositions and methods described herein.

The RI-labeled anti-MUC5AC humanized antibody of the present invention is a conjugate of a chelating agent chelated with a radionuclide and an antibody (the radionuclide is a metal nuclide that emits α particle or positron, and the antibody is a humanized antibody specifically binding to MUC5AC), and is superior in specificity for MUC5AC and accumulation in tumor. Therefore, it is extremely useful for the treatment and/or diagnosis of diseases in which MUC5AC is overexpressed, particularly cancer.

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 compositions and methods for treating cancers and proliferative disorders, including solid tumor cancers and non-myeloid hematological malignancies, using radioconjugates targeting CD33, alone or in combination with one or more radioconjugates targeting other cancer-associated targets such as DRS, 5T4, HER2, HER3, and TROP2, antibody drug conjugates targeting these or other cancer-associated targets, therapeutic antibodies targeting these or other cancer-associated targets, chemotherapy agents and regimens, and immune checkpoint inhibitors.

Disclosed herein are compounds, combinations, and kits that can be used to more quickly remove radionuclides from a subject, preferably a human being. Said compounds, combinations and kits can also be used to increase the tumor-to-blood ratio, or to more rapidly and/or conveniently achieve such an increase, of a label in targeted imaging or targeted radiotherapy in a subject, preferably a human being.