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: 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: 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: Methods for treating cancers and precancerous conditions by administering an effective amount of a radiolabeled agent that targets cell surface phosphatidylserine, alone or in combination with other therapies, are provided. The radiolabeled phosphatidylserine targeting agent delivers radiation to cells that externally present phosphatidylserine, such as tumor cells, depleting those cells and neighboring malignant cells to effect overall tumor reduction. Radiation delivered by the radiolabeled phosphatidylserine targeting agent itself increases the cell surface expression of phosphatidylserine, leading to a feed-forward mechanism that drives further accumulation of the phosphatidylserine targeting agent at target lesions to enhance its therapeutic effect.

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.

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: Provided are methods for treating a CD33-positive hematological malignancy, such as acute myelogenous leukemia or multiple myeloma, in a subject by administering to the subject hematopoietic stem cells (HSCs) or hematopoietic stem and progenitor cells (HSPCs) genetically modified to reduce or eliminate CD33 expression in myeloid cells derived therefrom in conjunction with antibody radioconjugates for one or both of conditioning the subject's bone marrow to receive and engraft the genetically modified stem cells and selectively depleting the subject's endogenous CD33-positive cells, including CD33-positive malignant cells.

Abstract: Methods for treating cancers and precancerous conditions by administering an effective amount of a radiolabeled agent that targets cell surface GRP78, alone or in combination with other therapies, are provided. The radiolabeled GRP78 targeting agent delivers radiation to cells that externally present GRP78, such as tumor cells, depleting those cells and neighboring malignant cells to effect overall tumor reduction. Radiation delivered by the radiolabeled GRP78 targeting agent itself increases the cell surface expression of GRP78, leading to a feed-forward mechanism that drives further accumulation of the GRP78 targeting agent at target lesions to enhance its therapeutic effect.

Abstract: Methods for treating cancers and precancerous conditions by administering an effective amount of a radiolabeled agent that targets cell surface calreticulin, alone or in combination with other therapies, are provided. The radiolabeled calreticulin targeting agent delivers radiation to cells that externally present calreticulin, such as tumor cells, depleting those cells and neighboring malignant cells to effect overall tumor reduction. Radiation delivered by the radiolabeled calreticulin targeting agent itself increases the cell surface expression of calreticulin, leading to a feed-forward mechanism that drives further accumulation of the calreticulin targeting agent at target lesions to enhance its therapeutic effect. Since cell surface expression of calreticulin is upregulated in response to cell damage and stress, radiolabeled calreticulin targeting agents may also be used in combination with other anticancer therapies to amplify their efficacy.

Abstract: Provided are compositions and methods for treating a solid or hematological cancer in a subject by administering an effective amount of a radioconjugated agent that targets one or more natural killer group 2, member D (NKG2D) ligands, alone or in combination with additional therapeutic agents or modalities. The radioconjugated NKG2DL-targeting agent targets NKG2DL-positive cells, such as tumor cells, depleting those cells and bystander NKG2DL-negative cells to effect overall tumor reduction. Moreover, radiation from the radioconjugated NKG2DL-targeting agent may increase expression of the target NKG2DL, leading to a feed-forward mechanism that further enhances the accumulation of the NKG2DL-targeting agent within the tumor.

Abstract: Provided are methods for treating a solid cancer in a subject by administering an effective amount of a radioconjugated CCR8-targeting agent to deplete tumor-associated CCR8-positive Treg cells, alone or in combination with one or more additional therapeutic agents or modalities, such as a radioconjugated CD33-targeting agent.

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?.