Biologic for the treatment of cancer
Inventors
PAYNE, Kimberly J. • FRANCIS-BOYLE, Olivia L.
Assignees
Publication Number
US-12016902-B2
Publication Date
2024-06-25
Expiration Date
2038-04-04
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Abstract
In one aspect, methods of treating a subject having a cancer that expresses a cytokine receptor are provided. In some embodiments, the method comprises administering to the subject a biologic agent in an amount sufficient to induce loss of cytokine receptor signaling through increased expression of a Suppressor of Cytokine Signaling genes and/or loss of one or more cytokine receptor components from the cancer cell surface. In some embodiments, the biologic agent is a cytokine or cytokine mimetic.
Core Innovation
The invention provides methods for treating a subject having cancer that expresses a cytokine receptor by administering a biologic agent, such as human thymic stromal lymphopoietin (TSLP), in an amount sufficient to induce loss of cytokine receptor signaling. This loss of signaling can arise through increased expression of Suppressor of Cytokine Signaling (SOCS) genes and/or loss of one or more cytokine receptor components from the cancer cell surface. The biologic agent can be a cytokine or cytokine mimetic.
The invention addresses the problem that current treatments for certain cancers, specifically leukemia subtypes like CRLF2 B-ALL, are associated with poor outcomes, particularly when there is overexpression of cytokine receptors such as CRLF2. Relapsed acute lymphoblastic leukemia (ALL) has survival rates of less than 50% in children and less than 12% in older adults, and available therapies have not significantly improved these statistics.
By targeting cancers that express or overexpress cytokine receptors—including leukemias and solid tumors—through administration of biologic agents that induce SOCS gene expression or loss of cell surface receptor, the invention provides a novel approach to disrupt critical cytokine signaling pathways implicated in cancer cell survival and proliferation. This targeted disruption is achieved by measuring and comparing the levels of CRLF2 and IL-7Rα and then administering TSLP when CRLF2 expression exceeds IL-7Rα, with the therapeutic aim of removing the survival advantage conferred by these receptors.
Claims Coverage
The independent claim focuses on a method for treating cancer patients using a specific biomarker-driven approach with TSLP treatment, detailing the requirements for protein expression assessment and therapeutic intervention.
Biomarker-driven TSLP therapy based on CRLF2 and IL-7Rα expression
The method includes: 1. Determining levels of interleukin-7 receptor-α (IL-7Rα) and cytokine receptor-like factor 2 (CRLF2) protein expression in a sample from the cancer patient. 2. Determining that the level of CRLF2 protein expression is greater than the level of IL-7Rα protein expression. 3. Administering a therapeutically effective amount of human thymic stromal lymphopoietin (TSLP) to the cancer patient, wherein the TSLP comprises the amino acid sequence set forth as SEQ ID NO: 1. This inventive feature specifically links therapeutic intervention to the molecular diagnostic status of CRLF2 and IL-7Rα, directing TSLP treatment only when CRLF2 protein expression exceeds that of IL-7Rα.
The claims cover a method for personalized cancer therapy that hinges on specific biomarker evaluation—using CRLF2 and IL-7Rα protein levels—to guide administration of TSLP, uniquely integrating molecular diagnosis and targeted treatment.
Stated Advantages
The method targets cytokine receptor-expressing cancer cells, leading to loss of critical cytokine receptor signaling through SOCS gene upregulation and/or reduction of receptor components on the cell surface.
This approach enables selective killing of cancer cells while supporting the expansion of normal B cell progenitors, which may help restore the immune system following chemotherapy.
Therapeutic intervention is guided by quantitative protein expression measurements, allowing for a biomarker-driven and personalized treatment strategy.
Documented Applications
Treatment of leukemias, including acute lymphoblastic leukemia (ALL), B-cell type ALL, Ph-like B-cell type ALL, acute myeloid leukemia (AML), and T-cell type ALL.
Treatment of solid tumors, including cervical, lung, and ovarian cancer.
Use in cancers characterized by overexpression of cytokine receptors, especially CRLF2, EGFR, or IL-7Rα.
Application in patient populations including both juvenile and adult subjects.
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