Provided are compositions and methods for treating cancers and precancerous proliferative disorders in a mammalian subject that involve the combination use of a radiotherapeutic agent, such as a radiolabeled CD33, DR5, 5T4, HER2, HER3, or TROP2 targeting agent, and a CD47 checkpoint inhibitor, such as a SIRPα-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRPα.

This invention provides a method for treating a subject afflicted with a hematologic malignancy comprising administering to the subject an agent targeting a hematologic malignancy-associated antigen, wherein the subject has a low peripheral cancerous cell burden. This invention also provides a method for treating a subject afflicted with a hematologic malignancy and having a high peripheral cancerous cell burden, comprising (i) medically lowering the subject's peripheral cancerous cell burden, and (ii) while the subject's peripheral cancerous cell burden is still low, administering to the subject an agent targeting a hematologic malignancy-associated antigen. Particularly envisioned are the subject methods for treating acute myeloid leukemia using an anti-CD33 antibody labeled with an alpha-emitting isotope, such as .sup.225Ac-HuM195.

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 anti-CLL-1 antibodies and immunoconjugates and methods of using the same.

Methods for treating a proliferative disease by administering a synergistic combination of an antibody against an epitope of CD33 (anti-CD33) and a combination of two or more individual chemotherapeutic agents is disclosed. The combination of chemotherapeutic agents may include cladribine, cytarabine, mitoxantrone, and filgrastim (CLAG-M), and the anti-CD33 may be a humanized monoclonal antibody against CD33 such as HuM195 conjugated with a radionuclide such as .sup.131I or .sup.225Ac. The proliferative disease or disorder may be a hematological disease such as multiple myeloma, acute myeloid leukemia, and/or myelodysplastic syndrome. The method may be particularly useful for treatment of relapsed or refractory acute myeloid leukemia.

The present disclosure relates to a WT1 peptide having a cysteine residue and including 10 to 12 residues, a peptide conjugate containing the same, and a combination of the WT1 peptide or the peptide conjugate and a WT1 helper peptide.

The present invention relates to a combination of radioimmunoconjugates and a protein or molecule capable of leading to progression of the cell cycle through the G2/M checkpoint, a protein or molecule capable of inhibiting progression through Mitosis, a protein or molecule which is a BCL2 inhibitor, or a protein or molecule which is a PARP inhibitor, for use as a medicament. The medicament may be against Non-Hodgkin's lymphoma (NHL).

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.

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.

The application provides polypeptides comprising or essentially consisting of at least one heavy chain variable domain of a heavy chain antibody (V.sub.HH) or a functional fragment thereof, wherein said V.sub.HH or a functional fragment thereof specifically binds to a target protein that is present on and/or specific for a solid tumor, e.g. HER2. The application further provides nucleic acids encoding such polypeptides; methods for preparing such polypeptides; host cells expressing or capable of expressing such polypeptides; compositions, and in particular to pharmaceutical compositions, that comprise such polypeptides, nucleic acids and/or host cells. The application further provides such polypeptides, nucleic acids, host cells and/or compositions, for use in methods for detection, imaging, prognosis and diagnosis of cancer as well as for predicting patient response(s) to therapeutics.