Anti-CD45-based conditioning methods and uses thereof in conjunction with gene-edited cell-based therapies
Inventors
Berger, Mark • Thomas, Keisha • Seth, Sandesh • Ludwig, Dale Lincoln
Assignees
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Publication Number
US-11912780-B2
Publication Date
2024-02-27
Expiration Date
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.
Core Innovation
The invention provides a method for depleting a human subject's hematopoietic stem cells in preparation for administration of a genetically edited hematopoietic stem cell therapy by administering an effective amount of a radiolabeled anti-CD45 antibody. The radiolabeled anti-CD45 antibody is radiolabeled BC8 comprising 131I or 225Ac.
The method is directed to subjects afflicted with a non-cancerous disorder treatable via genetically edited hematopoietic stem cell therapy, where the non-cancerous disorder is selected from hemoglobinopathy, congenital immunodeficiency, and viral infection. Depleting hematopoietic stem cells consists of reducing a population of hematopoietic stem cells by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 99%.
For the radiolabeled BC8, the invention requires 131I-BC8 with an effective amount from 10 mCi to 1,200 mCi or requires 225Ac-BC8 with an effective amount selected from specified ranges of 0.1 μCi/kg to 5.0 μCi/kg based on subject weight. A related treatment method includes performing the genetically edited hematopoietic stem cell therapy after a suitable time period, including allogeneic or autologous stem cell therapy.
Claims Coverage
The partial content identifies three independent claims. Each centers on radiolabeled BC8 for hematopoietic stem cell depletion by at least 10% to 99%, with isotope-specific effective amount ranges and sequencing with genetically edited hematopoietic stem cell therapy where applicable.
Radiolabeled anti-CD45 BC8 for hematopoietic stem cell depletion before genetically edited therapy
Administering an effective amount of a radiolabeled anti-CD45 antibody, where the radiolabeled anti-CD45 antibody is radiolabeled BC8 comprising 131I or 225Ac, for depleting hematopoietic stem cells in preparation for administration of a genetically edited hematopoietic stem cell therapy, wherein depletion consists of reducing a population of hematopoietic stem cells by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 99%.
Non-cancerous disorder selection for BC8-depletion-based genetically edited therapy
Limiting the treated subject to being afflicted with a non-cancerous disorder treatable via genetically edited hematopoietic stem cell therapy, where the non-cancerous disorder is selected from the group consisting of a hemoglobinopathy, a congenital immunodeficiency, and a viral infection.
Isotope-specific effective amounts for radiolabeled BC8
Defining the radiolabeled BC8 as either 131I-BC8 with an effective amount from 10 mCi to 1,200 mCi, or as 225Ac-BC8 with an effective amount selected from the group consisting of from 0.1 μCi/kg to 5.0 μCi/kg subject weight and corresponding listed subranges.
Sequential depletion and genetically edited stem cell therapy after a suitable time period
Administering an effective amount of a radiolabeled anti-CD45 antibody effective to deplete hematopoietic stem cells, where the radiolabeled anti-CD45 antibody is radiolabeled BC8, and then after a suitable time period performing the genetically edited hematopoietic stem cell therapy to treat the non-cancerous disorder.
Allogeneic or autologous genetically edited hematopoietic stem cell therapy following BC8 depletion
Requiring that the genetically edited hematopoietic stem cell therapy is allogeneic or autologous stem cell therapy in the treating method.
Article of manufacture with radiolabeled BC8 and a label instructing administration to deplete hematopoietic stem cells
Providing an article of manufacture consisting essentially of a radiolabeled anti-CD45 antibody, wherein the radiolabeled anti-CD45 antibody is radiolabeled BC8, and a label instructing a user to administer to a human subject an amount of the antibody effective to deplete hematopoietic stem cells, wherein depletion consists of reducing a population of hematopoietic stem cells by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 99%, with 131I-BC8 (10 mCi to 1,200 mCi) or 225Ac-BC8 (0.1 μCi/kg to 5.0 μCi/kg subject weight and listed subranges).
The inventive coverage is the use of radiolabeled BC8 (anti-CD45 comprising 131I or 225Ac) to deplete hematopoietic stem cells by at least 10% to 99% as preparation for or sequencing with genetically edited hematopoietic stem cell therapy for non-cancerous disorders, with isotope-specific effective amount ranges. The claims also extend this concept to an article of manufacture containing the radiolabeled antibody and an instructing label.
Stated Advantages
Radiolabeled, targeted conditioning avoids toxicity of chemotherapy or total lymphoid radiation, as stated.
Can improve therapy outcomes, as stated.
Documented Applications
Non-cancerous disorders treated via genetically edited hematopoietic stem cell therapy, including hemoglobinopathies, congenital immunodeficiencies, and viral infection.
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