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Means And Methods For Active Cellular Immunotherapy Of Cancer By Using Tumor Cells Killed By High Hydrostatic Pressure and Dendritic Cells

a cancer and tumor cell technology, applied in the direction of immunological disorders, drug compositions, antibody medical ingredients, etc., can solve the problems of not having the capacity, not providing activating signals, and irradiated killed tumor cells, so as to improve the prognosis of cancer patients, slow down or even stabilize the progression of the disease, and prevent the formation of metastases

Inactive Publication Date: 2013-01-10
SOTIO AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a novel process for inducing an immunogenic death of human tumor cells. High hydrostatic pressure (HHP) is used to kill tumor cells, which then become immunogenic and can stimulate dendritic cells. The combination of tumor cells and dendritic cells results in the efficient presentation of tumor antigens and the induction of strong anti-tumor immune responses. The method is more effective than existing chemotherapies and can reduce the distribution of tumor cells and metastasis. It is estimated that treatment with HHP-killed tumor cells can induce a tumor-specific immune response that will control the growth of tumor cells and improve progression of cancer patients. The patent also describes the use of leukapheresis to isolate and prepare dendritic cells for cancer immunotherapy.

Problems solved by technology

When used for pulsing of antigen presenting cells, such as dendritic cells, irradiated killed tumor cells do not provide an activating signal.
Tumor cells are not or only weakly immunogenic and they usually do not have the capacity to induce a tumor specific immune response if used in the absence of a powerful adjuvant.

Method used

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  • Means And Methods For Active Cellular Immunotherapy Of Cancer By Using Tumor Cells Killed By High Hydrostatic Pressure and Dendritic Cells
  • Means And Methods For Active Cellular Immunotherapy Of Cancer By Using Tumor Cells Killed By High Hydrostatic Pressure and Dendritic Cells
  • Means And Methods For Active Cellular Immunotherapy Of Cancer By Using Tumor Cells Killed By High Hydrostatic Pressure and Dendritic Cells

Examples

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Effect test

example 1

Expression of Immunogenic Cell Death Markers hsp70, hsp90 and Calreticulin by Human Cancer Cell Lines and Human Primary Tumor Cells after the Treatment with High Hydrostatic Pressure

[0089]Leukemic, ovarian and prostate cancer cell lines and primary tumor cells were treated for 10 min with high hydrostatic pressure (HHP, 200 MPa) at 21 degrees centigrade's and the expression of the known immunogenic cell death markers hsp70, hsp90 and calreticulin was monitored at 6, 12 and 24 h. Significant expression of calreticulin, hsp70 and hsp90 was detected 6, 12 and 24 h after HHP treatment for all tested tumor models. The expression of immunogenic molecules was significantly higher than the expression induced by anthracyclins, the only known inducers of immunogenic cell death (FIG. 2). Increased expression of calreticulin and heat shock proteins after HHP treatment was accompanied by their translocation to the cell surface. HHP treatment also induced a rapid and substantial release of HMGB1,...

example 2

Treatment of Tumor Cells by High Hydrostatic Pressure Increases their Phagocytosis by Antigen Presenting Cells

[0091]In view of the established role of calreticulin as an ‘eat me’ signal, the rate of phagocytosis of tumor cells killed by high hydrostatic pressure by dendritic cells (DCs) was investigated, the most efficient antigen presenting cells that are crucial for the initiation of an immune response. High hydrostatic pressure treated tumor cells were phagocytosed at faster rate and to a higher extent than the tumor cells killed by other modalities, such as anthracyclines or UV irradiation. After 12 h, the extent of phagocytosis of leukemic cells treated with HHP was 4-fold higher than of cells killed by UV irradiation (FIGS. 4a and 4b).

example 3

Phagocytosis of High Hydrostatic Pressure-Treated Tumor Cells Induces the Maturation of DCs

[0092]The ability of DCs to activate the immune response depends on their activation status and the expression of costimulatory molecules. In normal circumstances the most efficient maturation of DCs is induced by molecules derived from pathogens, such as lipopolysacharide (LPS) from Gram negative bacteria. Only activated (mature) DCs that express high levels of costimulatory molecules can initiate the immune response. We analyzed the phenotype of DCs that phagocytosed tumor cells killed by the HHP. The interaction of DCs with HHP-treated tumor cells induced the upregulation of costimulatory molecules (CD86, CD83) and maturation associated molecules (HLA-DR) to a similar extent as activation by LPS (FIG. 5). Thus tumor cells killed by HHP can induce DCs maturation comparable to pathogen derived LPS.

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Abstract

Disclosed are pharmaceutical compositions for inducing an immune response against tumor cells comprising tumor cells which are made apoptotic by treatment with high hydrostatic pressure and dendritic cells, and methods for producing such compositions.

Description

PRIORITY[0001]The present application claims the benefit of U.S. Provisional Application Ser. No. 61 / 504,387 filed Jul. 5, 2011, the entire contents of which are incorporated by reference herein.BACKGROUND OF THE PRESENT INVENTION[0002]Diseases caused by different tumors are still major problems in medicine and human health. The combination of surgery, chemotherapy and radiotherapy greatly improved the prognosis of cancer patients. Despite that this approach results frequently in a significant reduction of tumor mass, a small population of precursor tumor cells or cancer stem cells often survives and subsequently gives rise to a new population of tumor cells that leads to a relapse. Even if the main tumor is removed by surgical and / or other treatments minor amounts of circulating tumor cells may cause metastatic tumors in different areas of the body. Therefore, there exists a permanent need for alternative medicaments and methods of treatment which may be used alone or preferably be...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61P37/04
CPCA61K39/0011A61K2039/5152A61K2039/572A61K2039/5154A61P37/04A61K2039/80A61K39/4622A61K39/464494A61K39/464499A61K39/4644A61K39/4615
Inventor BARTUNKOVJIRINASP SEK, RADEK
Owner SOTIO AS
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