Cancer treatments with radiation and immunocytokines

A technology of immune cells and cytokines, which is applied in the field of treating tumors and cancer cells, and can solve problems such as no improvement and dyspnea

Inactive Publication Date: 2011-09-21
MERCK PATENT GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Also, some cancer types show no improvement after treatment
In addition, IL-2 is known to produce serious side effects, including vascular leakage syndrome, in which fluid leaks from blood vessels, causing hypotension, dyspnea, and edema

Method used

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  • Cancer treatments with radiation and immunocytokines
  • Cancer treatments with radiation and immunocytokines
  • Cancer treatments with radiation and immunocytokines

Examples

Experimental program
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Embodiment Embodiment 1

[0080]In accordance with the methods of the present invention, third parties, such as hospitals, clinics, government entities, reimbursers, insurance companies (e.g., health insurance companies), HMOs, third-party payers, or other entities that pay for or reimburse medical expenses may approve treatment, approval as Payment for treatment or approval for reimbursement for treatment. For example, the invention relates to health care methods that include authorizing administration of an immunocytokine to a mammal having previously irradiated tumor or cancer cells, or authorizing payment or reimbursement for administration of an immunocytokine. For example, the health care method may include an approved dose of at least 1 Gy / day (e.g., at least 2, at least 3, 1-4, 1-10, 1-20, 2-4, 2-10, 2-20, 3-4, 3-10 or 3-20 Gy / day), administration of immunocytokine to mammals with previously irradiated tumors, or approval of payment or reimbursement for administration of immunocytokine. The he...

Embodiment 2

[0097] Student's two-tailed t-test or Mann-Whitney rank sum test was performed on individual tumor volumes or animal body weights, as appropriate, to determine significant differences between treatment groups. Example 2: Effect of Immunocytokine Therapy After a Single Dose of Radiation

[0098] A single dose of post-radiation intravenous immunocytokine (5 mg / kg). Unless otherwise specified, this and the following examples use the exemplary immunocytokine dI-NHS76γ2(h)(FN>AQ)-ala-IL2(D20T), also named Selectikine or EMD521873, and described in, e.g. U.S. Patent No. 7,186,804.

[0099] In three separate experiments using the CT26 / KSA model (experiments CT26-1-3), administration of EMD521873 at days 2, 3 and 4 following tumor irradiation with 3 or 4 Gy resulted in a strong synergistic effect, with most animals achieving complete subside. ELISPOT analysis using endogenous CT26 antigen showed a >4-fold increase in T cell responses compared to either therapy alone. A 4-fold in...

Embodiment 3

[0101]The antitumor effect of an exemplary immunocytokine EMD521873 (5 mg / kg) administered intravenously on days 7, 8, and 9 following five daily doses of 3.6 Gy on days 0 to 4 was evaluated in a Lewis lung cancer model (Experimental LLC-1, LLC-2). No complete responses were observed in the control or monotherapy groups, whereas 3 / 6 animals achieved a complete response with the combination. Gene expression profiling using a panel of immune markers showed that the combination increased T-cell markers, T-cell activation, lymphocyte trafficking, and Th1 responses compared to radiation or EMD521873 alone. Upregulated genes include CD45, CISH, CD122, MGP, FASL, CD80, PTPRB, CD6, CCR7, TXK, CTLA4, PDCD1, IL10R, CCL6, CD8A, EOMES, CD28, TγROBP, ICAM1, CD206, VCAM1, CD3G, ITGAL, ITGB2, LAT, GZMK, STAT4, IL1A, CD115, MDM2, CD26, GIMAP3, CXCR4, LCK, HS6ST2. Downregulated genes included IL23A, SELE, SC4MOL, LDLR, SQLE, RAE1, CXCL1, CCL2. Example 4: Effect of Adding Chemotherapy to the...

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Abstract

The present invention is directed to a method for treating tumors and cancer cells by administering an immunocytokine following radiation treatment. This combination of treatments can stimulate an immune response at irradiated and non-irradiated sites, which is useful in eradicating cancer cells that have spread from the site of the primary tumor. In addition, immunocytokines can be administered at a dose that is less that the maximum tolerated dose, which reduces the side effects associated with immunocytokine therapy.

Description

technical field [0001] The present invention relates to methods of treating tumors and cancer cells by administering immunocytokines following radiation therapy. This combination of treatments can stimulate an immune response at both irradiated and non-irradiated sites, which is used to eliminate cancer cells that have spread from the primary tumor site. Furthermore, with this therapy, immunocytokine, preferably NHS-IL2(D20T) and NHS-IL12, can be administered at doses lower than the maximum tolerated dose, which reduces the side effects associated with immunocytokine therapy. Background technique [0002] Effective treatment of diseases such as cancer requires a potent immune response from one or more effector cell types, such as natural killer (NK) cells, macrophages and T lymphocytes. However, existing cancer treatments, such as radiation therapy and chemotherapy, target rapidly dividing cells and thereby actually destroy immune cells. Furthermore, the environment of the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/20
CPCA61K38/2013A61K38/208A61N5/10A61P35/00A61P37/04A61K38/20
Inventor T·威克姆U·格纳德-福格特S·G·克林兹S·A·霍尔登K·J·卡伦
Owner MERCK PATENT GMBH
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