Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure

A technology of tumor cells and dendritic cells, applied in the field of pharmaceutical compositions for immune response, can solve the problems of tumor size reduction, deterioration of tumor cells, etc.

Inactive Publication Date: 2013-01-09
SOTIO AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although these approaches lead to a dramatic reduction in tumor size, often a small population of precursor tumor cells or cancer stem cells survives, giving rise to a new population of tumor cells that lead to progression

Method used

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  • Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure
  • Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure
  • Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure

Examples

Experimental program
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Effect test

Embodiment 1

[0092] Expression of the immunogenic cell death markers hsp70, hsp90, and calreticulin in human cancer cell lines and human primary tumor cells following treatment with high hydrostatic pressure

[0093] Leukemia, ovarian and prostate cancer cell lines and primary neoplastic cells were treated with high hydrostatic pressure (HHP, 200MPa) at 21°C for 10 minutes and hsp70, a known immunogenic cell death marker, was monitored at 6, 12 and 24 hours , hsp90 and calreticulin expression. Significant expression of the immunogenic cell death markers calreticulin, hsp70 and hsp90 was detected 6, 12 and 24 hours after HHP treatment in all tumor models tested. The expression of these immunogenic molecules was significantly higher than that induced by anthracyclines, the only known inducers of immunogenic cell death ( figure 2 ). The increased expression of calreticulin and heat shock proteins after HHp treatment was accompanied by their translocation on the cell surface. HHp treatment...

Embodiment 2

[0096] High hydrostatic pressure treatment of tumor cells enhances their phagocytosis by antigen-presenting cells

[0097] The rate of phagocytosis of tumor cells killed by high hydrostatic pressure by dendritic cells (DCs), the most efficient antigen-presenting cells, which are critical for the initiation of an immune response. High hydrostatic pressure treated tumor cells were phagocytosed at a faster rate and to a higher extent than tumor cells killed by other means such as anthracycline antibiotics and UV radiation. After 12 hours, the degree of phagocytosis of leukocytes treated with HHP was 4 times that of cells killed by UV radiation ( Figure 4 a and Figure 4 b).

Embodiment 3

[0099] Phagocytosis of high hydrostatic pressure-treated tumor cells induces maturation of DCs.

[0100] The ability of DCs to activate immune responses depends on their activation status as well as the expression of co-stimulatory molecules. Under normal circumstances, the maturation of the most efficient DCs is induced by pathogen-derived molecules, such as lipopolysaccharide (LPS) in Gram-negative bacteria. Only activated (mature) DCs expressing high levels of co-stimulatory molecules are able to elicit an immune response. We analyzed the phenotype of dendritic cells that phagocytized tumor cells killed by HHP. Interaction of DCs with HHP-treated tumor cells induced co-stimulatory factors (CD86, CD83) and maturation-associated molecules (HLA-DR) to a similar extent as activation by LPS ( Figure 5 ). Thus, tumor cells killed by HHP were able to induce maturation of DCs 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

technical field [0001] The present invention relates to a pharmaceutical composition for inducing an immune response against tumor cells, comprising dendritic cells and tumor cells treated with high hydrostatic pressure to cause apoptosis, and a method for preparing such a composition. Background technique [0002] Diseases caused by different tumors remain a major problem in medicine and human health. The combination of surgery, chemotherapy and radiation therapy has greatly improved the prognosis of cancer patients. Although these approaches lead to a dramatic reduction in tumor size, often a small population of precursor tumor cells, or cancer stem cells, survives, giving rise to a new population of tumor cells that lead to progression. Even after the primary tumor is removed through surgery and / or other treatments, rare numbers of circulating tumor cells can lead to metastatic tumors in other parts of the body. Therefore, there is always a need for different drugs and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/12A61K35/14A61P35/00C12N5/0784A61K39/00
CPCA61K2039/5154A61K39/00A61K2039/5152A61K39/0011A61P13/08A61P35/00A61P43/00A61K35/12A61K35/36C12N5/0639
Inventor J·巴图恩科娃R·斯皮塞克
Owner SOTIO AS
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