Method for treating cancer using a BCL-2 inhibitor in conjunction with an alpha-emitting radioimmunotherapeutic
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Publication Number
US-11844799-B2
Publication Date
2023-12-19
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 acute myeloid leukemia using combination pharmaceutical therapy that comprises administering venetoclax and, in conjunction, administering 225Ac-labeled HuM195. The treatment is directed to cancer cell death and apoptosis in the context of acute myeloid leukemia targeting by HuM195. The described regimen combines a BCL-2 inhibitor with an alpha-emitting isotope-labeled, tumor-targeting agent.
A central problem addressed is apoptotic resistance in acute myeloid leukemia and the limitations of beta radiation, including issues associated with tumor hypoxia and dose-range problems. The disclosure provides mechanistic support for overcoming apoptotic resistance and for promoting apoptosis through the alpha-emitting radiation approach. The alpha-radiation mechanism is described in terms of radiation-induced effects that support apoptosis-related pathways.
The disclosure further frames therapeutic concepts such as in conjunction, therapeutically effective, and dosing relationships, including sub-saturating dosing. It also defines therapeutic endpoints and discusses additional therapeutic contexts including radioimmunotherapy and pre-targeted radioimmunotherapy (PRIT). The disclosed examples include treatment concepts for AML using venetoclax together with 225Ac-HuM195, with related rationale grounded in apoptosis and radiation effects.
Claims Coverage
The partial content provides one independent claim and one dependent claim. The independent claim covers a combination pharmaceutical therapy for human acute myeloid leukemia using venetoclax together with 225Ac-labeled HuM195, and the dependent claim narrows the patient population to relapsed and/or refractory AML.
Combination pharmaceutical therapy for acute myeloid leukemia with venetoclax and 225Ac-labeled HuM195
A method for treating a human subject afflicted with acute myeloid leukemia comprising combination pharmaceutical therapy that administers venetoclax in conjunction with administering 225Ac-labeled HuM195.
Relapsed and/or refractory acute myeloid leukemia
The method wherein the acute myeloid leukemia is relapsed and/or refractory.
The inventive coverage is the use of venetoclax administered in conjunction with 225Ac-labeled HuM195 for treating human acute myeloid leukemia, with dependent narrowing to patients with relapsed and/or refractory disease.
Stated Advantages
Overcomes apoptotic resistance.
Addresses limitations of beta radiation, including tumor hypoxia and dose-range problems.
Promotes apoptosis and cancer cell death in acute myeloid leukemia via the combined approach.
Documented Applications
Treatment of a human subject afflicted with acute myeloid leukemia using combination pharmaceutical therapy comprising venetoclax and, in conjunction, 225Ac-labeled HuM195.
AML using venetoclax and 225Ac-HuM195 as described in the disclosure for cancer cell death and apoptosis contexts.
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