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KR-20260062965-A - Cancer treatments including antisense and interferon-gamma

KR20260062965AKR 20260062965 AKR20260062965 AKR 20260062965AKR-20260062965-A

Abstract

The present invention relates to agents, compositions, and methods for use in treating or improving symptoms of cancer. Representative synergistic therapies include the use of antisense oligonucleotide agonists to inhibit the expression of TGF-β2, both alone and in combination with interferon-gamma. One or more biomarkers may be used to select the treatment target.

Inventors

  • 찌에우, 브엉

Assignees

  • 지엠피 바이오테크놀로지 리미티드
  • 찌에우, 브엉

Dates

Publication Date
20260507
Application Date
20240830
Priority Date
20230830

Claims (20)

  1. An agonist for inhibiting the expression of TGF-β2 in combination with interferon-gamma for use in treating or improving symptoms of cancer in a subject in need, wherein (a) one or both of JAK1 and STAT1 are reduced and (b) TGF-β2 and IFNGR2 are elevated in a subject selected.
  2. (a) selecting a subject in which one or both of JAK1 and STAT1 are reduced and (b) TGF-β2 and IFNGR2 are elevated; Administering a composition comprising an agent for inhibiting the expression of TGF-β2; and Administering a composition containing interferon-gamma A method for treating or improving symptoms of cancer in a subject requiring it, including
  3. A composition comprising an agent for inhibiting the expression of TGF-β2 and a pharmaceutically acceptable carrier, for use in the manufacture of a drug for treating or improving symptoms of cancer in a subject in combination with interferon-gamma, wherein (a) one or both of JAK1 and STAT1 are reduced and (b) a subject having elevated TGF-β2 and IFNGR2 is selected.
  4. An agent, method, or composition according to any one of claims 1 to 3, wherein the cancer is a brain or spinal cord cancer, glioma, glioblastoma, diffuse intrinsic pontine glioma (DIPG), diffuse meningeal glioma (DMG), diffuse hemispheric glioma, or leptomeningeal or brain metastasis, or the cells of the cancer exhibit somatic mutations including H2-K27M, H3-K27M, or H3-G34 genomic variants.
  5. An agent, method, or composition according to any one of claims 1 to 3, wherein the agent for inhibiting the expression of TGF-β2 and interferon-gamma are administered in parallel, simultaneously, sequentially, or separately over time.
  6. An agent, method, or composition according to any one of paragraphs 1 to 3, wherein the composition and the agent are administered by injection or injection.
  7. An agent, method, or composition according to any one of claims 1 to 3, wherein one or both of JAK1 and STAT1 have mRNA levels reduced to below the median of a control group of subjects having the same cancer, and TGF-β2 and IFNGR2 are elevated above the median of a control group of subjects having the same cancer.
  8. An agent, method, or composition according to any one of claims 1 to 3, wherein the agent for inhibiting the expression of TGF-β2 is selected from Table 1 or Table 2, and its chemically modified variants, its LNA variants, its Gapmers variants, and any combination or mixture thereof.
  9. A method or composition according to any one of claims 1 to 3, wherein the agent for inhibiting or suppressing the expression of TGF-β2 is C*G*G*C*A*T*G*T*C*T*A*T*T*T*T*G*T*A sequence identification number: 137 (OT-101) or CGGCATGTCTATTTTGTA sequence identification number: 1.
  10. An agent, method, or composition according to any one of claims 1 to 3, wherein the interferon-gamma is human recombinant interferon-gamma.
  11. An agent, method, or composition according to any one of claims 1 to 3, wherein the agent or composition comprises a carrier which is sterile water for injection, saline solution, isotonic saline solution, or a combination thereof.
  12. An agent, method, or composition according to any one of paragraphs 1 to 3, wherein the agent or composition is substantially free of excipients.
  13. An agent, method, or composition according to any one of claims 1 to 3, wherein the composition is stable for at least 14 days in a carrier at 37°C.
  14. An agent, method, or composition according to any one of claims 1 to 3, wherein the subject exhibits reduced TGF-β2 expression upon administration or use.
  15. An agent, method, or composition according to any one of paragraphs 1 to 3, wherein administration or use reduces mortality at 6, 12, 18, 24, 30, or 36 months.
  16. An agent, method, or composition according to any one of claims 1 to 3, wherein administration or use increases survival rate at 6, 12, 18, 24, 30, or 36 months.
  17. An agent, method, or composition according to any one of claims 1 to 3, wherein the administration or use of the composition is combined with standard management treatment for cancer, wherein the standard management treatment includes chemotherapy or radiation therapy.
  18. An agent for inhibiting the expression of TGF-β2 for use in treating or improving symptoms of cancer in a subject in need, wherein (a) a subject in which IFNGR2 is elevated and (b) a subject in which TGF-β2 is elevated is selected.
  19. (a) selecting subjects in which IFNGR2 is elevated and (b) TGF-β2 is elevated; and Administering a composition containing an agent for inhibiting the expression of TGF-β2 A method for treating or improving symptoms of cancer in a subject requiring it, including
  20. A composition comprising an agent for inhibiting the expression of TGF-β2 and a pharmaceutically acceptable carrier for use in the manufacture of a drug for treating or improving symptoms of cancer in a subject, wherein (a) a subject having elevated IFNGR2 and (b) elevated TGF-β2 is selected.

Description

Cancer treatments including antisense and interferon-gamma [Ranking List] The present application includes a sequence list created on August 27, 2024, and electronically submitted as an ST.26 file named 018988-013WO1_SL.xml, with a size of 120,204 bytes. [Technology Field] The present invention relates to agents, compositions, and methods for use in treating or improving symptoms of cancer. Representative synergistic therapies include active agents for inhibiting the expression of TGF-β2, both alone and in combination with interferon-gamma. One or more biomarkers may be used to select the treatment target. Cancer is a complex pathological condition associated with numerous mutated cellular pathways. Due to this complexity, many anticancer drugs have limited or partial therapeutic efficacy. Limitations of conventional treatments include a lack of efficacy, as determined by overall survival. In some cases, surgical resection is not possible due to the anatomical location of the tumor. Other drawbacks of conventional treatments include significant unwanted side effects, such as the death of healthy cells in addition to killing cancer cells. An additional drawback of anticancer agents includes high toxicity at the required levels of therapeutic administration. In some cases, monotherapy cannot be a feasible strategy because the presence and level of the therapeutic target may be variable. What is needed are agents, compositions, and methods for cancer that increase efficacy while reducing toxicity and unwanted side effects. Therapeutics involving combinations of active agents can enhance therapeutic effects. Furthermore, guidance from biomarkers can be a powerful tool for improving therapies. To provide substantial anti-tumor and cancer immunotherapeutic effects, and to enhance efficacy, reduce side effects, and minimize negative health effects, therapeutic compositions of different agents are required. There is a need for enhanced guidance on the use of such compositions by using appropriate biomarkers to select the synergistic effects of the agents and compositions. [Summary of the Invention] The present invention provides agents, compositions, and methods for use in treating or improving the symptoms of cancer. The synergistic drug therapy of the present invention includes the use of potent anti-tumor agents alone or in combination with interferon-gamma. The cancer treatment modes of the present disclosure include selecting patients and cancers for the therapy through biomarkers and disease variants to improve outcomes. Embodiments of the present invention relate to inhibiting high TGF-β2 expression levels that can be performed in combination with interferon-gamma, and selecting patients based on specific biomarker levels. Another embodiment of the present invention includes inhibiting high TGF-β2 expression levels alone and selecting patients based on biomarkers. In some embodiments, the method and therapeutic strategy of the present invention may include increased guidance for successful patient outcomes using appropriate biomarkers for selecting synergistic effects of the composition and agent. In some embodiments, selecting cancer patients with elevated IFNGR2 can improve clinical outcomes. Embodiments of the present invention include the following: (a) an agonist for inhibiting the expression of TGF-β2 in combination with interferon-gamma for use in treating or improving symptoms of cancer in a subject in need, wherein one or both of JAK1 and STAT1 are reduced and (b) a subject in which TGF-β2 and IFNGR2 are elevated may be selected. A method for treating or improving symptoms of cancer in subjects in need, which may include the following: (a) selecting a subject in which one or both of JAK1 and STAT1 are reduced and (b) TGF-β2 and IFNGR2 may be elevated; Administering a composition comprising an agent for inhibiting the expression of TGF-β2; and Administering a composition containing interferon-gamma. (a) a composition comprising an agent for inhibiting the expression of TGF-β2 and a pharmaceutically acceptable carrier for use in the manufacture of a drug for treating or improving symptoms of cancer in a subject in combination with interferon-gamma, wherein one or both of JAK1 and STAT1 are reduced and (b) a subject having elevated TGF-β2 and IFNGR2 may be selected. The agent, method, or composition wherein the cancer may be brain or spinal cord cancer, glioma, glioblastoma, diffuse intrinsic pontine glioma (DIPG), diffuse meningeal glioma (DMG), diffuse hemispheric glioma, or leptomeningeal or brain metastasis, or wherein the cells of the cancer exhibit somatic mutations including H2-K27M, H3-K27M, or H3-G34 genomic variants. The agent, method, or composition for inhibiting the expression of TGF-β2 and interferon-gamma may be administered in parallel, simultaneously, sequentially, or separately over time. The agent, method, or composition in which the composition and agent can be administered by injec