Abstract: This invention provides a method for depleting a subject's hematopoietic stem cells comprising administering to the subject an effective amount of a radiolabeled anti-CD45 antibody, such as 131I-BC8 or 225Ac-BC8. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy comprising (i) administering to the subject an amount of a radiolabeled anti-CD45 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.

Abstract: This invention provides a method for depleting a subject's hematopoietic stem cells comprising administering to the subject an effective amount of a radiolabeled anti-CD45 antibody, such as 131I-BC8 or 225Ac-BC8. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy comprising (i) administering to the subject an amount of a radiolabeled anti-CD45 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.

Abstract: 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 DR5, 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.

Abstract: 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 225Ac, 177Lu, 131I, 90Y, 213Bi, 211At, 213Bi, 227Th, or 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.

Abstract: Methods for treating a hematological disease or disorder or a solid cancer by administering an effective amount of a combination immunotherapy including an antibody against an epitope of CD33 and an antibody against an epitope of CD38 are disclosed. One or both of the anti-CD33 and anti-CD38 antibodies may be labeled with a radioisotope. The antibodies may be administered sequentially or simultaneously. Moreover, each antibody may be administered according to a specific dosing schedule, wherein the administration may be sequential (i.e., one antibody dosing schedule is completed before the next antibody dosing schedule is started) or simultaneous.

Abstract: 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.

Abstract: 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 SIRP?-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRP?.

Abstract: 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 SIRP?-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRP?.

Abstract: 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 SIRP?-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRP?.

Abstract: 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 225Ac, 177Lu, 131I, 90Y, 213Bi, 211At, 213Bi, 227Th, or 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.

Abstract: This invention provides a compositions of matter comprising a therapeutic protein population (such as a HuM195 antibody population) wherein (a) each therapeutic protein in the population is conjugated to one or more actinium atoms, (b) each actinium atom is either 227Ac or 225Ac, and (c) the molar ratio of 227Ac to 225Ac in the composition is at least 1:1, This invention also provides related synthetic compositions and methods, as well as methods for treating hematologic malignancies.

Abstract: This invention provides a method for treating a subject afflicted with cancer, comprising administering to the subject (i) a PARP inhibitor in conjunction with (ii) a radioisotope-labeled agent that targets cancer cells in the subject, wherein the amounts of the PARP 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 PARP inhibitor in conjunction with (ii) a radioisotope-labeled agent that targets the cancer cell, wherein the amounts of PARP inhibitor and labeled agent, when concurrently contacted with the cell, are effective to induce the cell's death.

Abstract: This invention provides a method for depleting a subject's immune cells, where the method includes administering to the subject an effective amount of a radiolabeled anti-CD45 antibody. This invention also provides a method for treating a subject afflicted with cancer, where the method includes (i) administering to the subject an amount of a radiolabeled anti-CD45 antibody effective to deplete the subject's lymphocytes, and (ii) after a suitable time period, performing adoptive cell therapy on the subject to treat the subject's cancer. Finally, this invention provides an article of manufacture including (a) a radiolabeled anti-CD45 antibody, and (b) a label instructing the user to administer to a subject an amount of the antibody effective to deplete the subject's immune cells.

Abstract: Methods for the treatment of a proliferative disorder include administration of a radiolabeled anti-CD45 antibody in concert with an adoptive cell therapy. The adoptive cell therapy may include administration of cells expressing a chimeric antigen receptor or a T-cell receptor (CAR/TCR). The radiolabeled anti-CD45 antibody may be administered before administration of the population of cells expressing the CAR/TCR, either alone or in conjunction with standard lymphodepletion agents. The radiolabeled anti-CD45 antibody may be administered after administration of the population of cells expressing the CAR/TCR in preparation for transplantation of autologous stem cells and/or administration of a second effective amount of the populations of cells expressing the CAR/TCR. These methods may improve treatment outcomes for hematological malignancies including solid tumors, and/or may lessen side effects associated with adoptive cell therapies.

Abstract: Methods for treating a hematological disease or disorder or a solid cancer by administering an effective amount of a combination immunotherapy including an antibody against an epitope of CD33 and an antibody against an epitope of CD38 are disclosed. One or both of the anti-CD33 and anti-CD38 antibodies may be labeled with a radioisotope. The antibodies may be administered sequentially or simultaneously. Moreover, each antibody may be administered according to a specific dosing schedule, wherein the administration may be sequential (i.e., one antibody dosing schedule is completed before the next antibody dosing schedule is started) or simultaneous.

Abstract: This invention provides a method for depleting a subject's hematopoietic stem cells comprising administering to the subject an effective amount of a radiolabeled anti-CD45 antibody, such as 131I-BC8 or 225Ac-BC8. This invention also provides a method for treating a subject afflicted with a non-cancerous disorder treatable via genetically edited cell therapy comprising (i) administering to the subject an amount of a radiolabeled anti-CD45 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.

Abstract: Pharmaceutical compositions comprising a radionuclide labelled monoclonal antibody against CD38, and methods of treating a hematological malignancy, inhibiting growth and/or proliferation of a cell expressing CD38, or treating a disease or disorder involving cells expressing CD38 are disclosed. An exemplary monoclonal antibody includes daratumumab labeled with actinium (225Ac).