Method for treating cancer using a BCL-2 inhibitor in conjunction with an alpha- emitting radioimmunotherapeutic
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Publication Number
US-12133849-B2
Publication Date
2024-11-05
Expiration Date
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.
Core Innovation
The invention relates to a method for treating a human subject afflicted with a hematological malignancy using combination pharmaceutical therapy. The combination pharmaceutical therapy comprises administering venetoclax to the subject in conjunction with administering 225Ac-labeled HuM195 to the subject.
The alpha-emitting isotope in the 225Ac-labeled HuM195 supports inducing death of a cancer cell through concurrent administration with a BCL-2 inhibitor. The background problem addressed includes overcoming apoptotic resistance and limitations associated with radiation mechanisms, including oxygenation/hypoxia effects and dose-range issues.
In an acute myeloid leukemia embodiment, the document describes combining venetoclax with 225Ac-HuM195 (lintuzumab), including anti-CD33 targeting. The effectiveness and therapeutic outcomes are described using defined therapeutic endpoints, with considerations including sub-saturating dosing and peripheral blast burden.
Claims Coverage
The independent claim covers a combination pharmaceutical therapy defined by two concurrent administrations, venetoclax and 225Ac-labeled HuM195, for treating a human subject with selected hematological malignancies. The claim set includes one inventive feature in the core combination, while dependent claims narrow the hematological malignancy selection into specific myelodysplastic syndrome and myeloproliferative disorder subtypes.
Combination of venetoclax with 225Ac-labeled HuM195 for hematological malignancy
Administering venetoclax to a human subject in conjunction with administering 225Ac-labeled HuM195 as combination pharmaceutical therapy for treating a hematological malignancy selected from myelodysplastic syndrome and a myeloproliferative disorder.
Overall coverage is focused on the same therapeutic combination structure, venetoclax administered together with 225Ac-labeled HuM195, while dependent claims narrow the covered disease selection to specific subtypes within myelodysplastic syndrome and myeloproliferative disorders.
Stated Advantages
The approach supports inducing death of a cancer cell through concurrent administration with a BCL-2 inhibitor.
The disclosed approach addresses apoptotic resistance and limitations associated with radiation mechanisms, including oxygenation/hypoxia effects and dose-range issues.
Documented Applications
Treatment of a human subject afflicted with a hematological malignancy.
An acute myeloid leukemia embodiment involving venetoclax and 225Ac-HuM195 (lintuzumab), including anti-CD33 targeting.
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