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 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 131I or 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.

Abstract: 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.

Abstract: The present disclosure provides epitopes of CD45, and binding agents such as antibodies, antibody fragments, peptides, and small molecules capable of binding to those epitopes. The present disclosure also provides methods of treating cancers, hematological diseases and disorders, and immune diseases and disorders, using these binding agents.

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: Methods for treating a proliferative disease in hematologic malignancy in a subject having a complex karyotype by administering an effective amount of an immunotherapy which includes a targeting agent for an epitope of CD33. The proliferative disease may be a hematological disease or disorder such as multiple myeloma, acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasm. The effective amount of the anti-CD33 targeting agent may be an amount sufficient to induce myeloconditioning or an amount to induce myeloablation. The methods may further include transplanting allogeneic stem cells to the patient after administration of the anti-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: A patient specific therapeutic composition provided in a single dose container, the total volume of which may be administered to a patient in a single treatment session. The composition includes a monoclonal antibody having a labeled fraction and an unlabeled fraction, and a pharmaceutically acceptable carrier. The label may be any of a radioisotope or a drug such as a chemotherapeutic or cytotoxic agent. The amount of the monoclonal antibody and any conjugated label molecule may depend on at least one patient specific parameter selected from a patient weight, a patient age, a patient height, a patient gender, a patient medical condition, and a patient medical history. Methods of administration, production, and articles of manufacture comprising the patient specific therapeutic composition are also disclosed.

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).

Abstract: Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radio-therapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.

Abstract: Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radiotherapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.

Abstract: 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 225Ac-HuM195.

Abstract: Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radio-therapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.

Abstract: The present disclosure discloses a manufacturing method of a polycrystalline silicon thin film, which includes: forming a first amorphous silicon thin film; crystallizing the first amorphous silicon thin film to form a polycrystalline silicon thin film by applying an excimer laser annealing process; forming a second amorphous silicon thin film on a first surface of the polycrystalline silicon thin film; and etching until the second amorphous silicon thin film is completely removed toward a direction of the polycrystalline silicon thin film from the second amorphous silicon thin film by applying a dry etching process. The present disclosure further discloses a manufacturing method of a thin film transistor array substrate which includes the steps of manufacturing an active layer: forming a layer of a polycrystalline silicon thin film according to the previous polycrystalline silicon thin film; and etching the polycrystalline silicon thin film to form a patterned active layer.

Abstract: Compositions and methods are described for stabilizing a radio-iodinated monoclonal IgG antibody for up to 17 days against radiolytic decomposition. The stabilized radiolabeled murine antibody binding the CD45 antigen expressed on various forms of lymphomas is useful as a radio-therapeutic and diagnostic agent in the treatment of human malignancies of hematopoietic origin, including lymphomas.

Abstract: The present invention describes a method for purification of 225Ac from irradiated 226Ra-targets provided on a support comprising a leaching treatment of the 225Ra-targets for leaching essentially for the entirety of 223Ac and 226Ra with nitric or hydrochloric acid, followed by a first extraction chromatography for separating 225Ac from 226Ra and other Ra-isotops and a second extraction chromotography for separating 225Ac from 210Po and 210Pb. The finally purified 225Ac can be used to prepare compositions useful for pharmaceutical purposes.

Abstract: Methods for generating an Ac-225 radioconjugate comprising a monoclonal antibody (mAb) (IgG) is disclosed. The Ac-225 radioimmunoconjugate is an [Ac-225]-p-SCN-Bn-DOT AIHuM195 radioimmunoconjugate.

Abstract: The present invention describes a method for purification of 225Ac from irradiated 226Ra-targets provided on a support, comprising a leaching treatment of the 226Ra-targets for leaching essentially the entirety of 225Ac and 226Ra with nitric or hydrochloric acid, followed by a first extraction chromatography separating 25Ac from 226Ra and other Ra-isotopes and a second extraction chromatography for separating 225Ac from 210Po and 210Pb. The finally purified 225Ac can be used to prepare compositions useful for pharmaceutical purposes.

Abstract: The present invention describes a method for purification of 225Ac from irradiated 226Ra-targets provided on a support, comprising a leaching treatment of the 226Ra-targets for leaching essentially the entirety of 225Ac and 226Ra with nitric or hydrochloric acid, followed by a first extraction chromatography for separating 225Ac from 226Ra and other Ra-isotops and a second extraction chromatography for separating 225Ac from 210Po and 210Pb. The finally purified 225Ac can be used to prepare compositions useful for pharmaceutical purposes.