Use of soluble CEACAM8 for diagnosing, treating or monitoring diseases, and a method for screening compounds that prevent apoptosis

Inventors

Singer, Bernhard

Assignees

Ymmunobio Ag

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Publication Number

US-8501192-B2

Patent

Publication Date

2013-08-06

Expiration Date


Abstract

The invention relates to new uses of soluble CEACAM6 or CEACAM8, or substances that are specific to soluble CEACAM8. Another object of the invention concerns the use of CEACAM1-specific and/or CEACAM6-specific compounds for apoptosis prevention in-vitro. The invention also relates to a method for screening compounds, which prevent apoptosis and a method for preventing apoptosis in human granulocytes.

Core Innovation

The invention relates to therapeutic and diagnostic uses of soluble CEACAM6 and soluble CEACAM8, including full-length soluble CEACAM8 and CEACAM8-specific substances. It is described that soluble CEACAM8 produced upon granulocyte priming binds strongly to membrane-anchored CEACAM1 and CEACAM6, while lacking CEACAM8 homophilic binding.

Pre-treatment with soluble CEACAM8 prevents CEACAM8-mAb-induced apoptosis in human granulocytes. The document also describes that soluble CEACAM6/CEACAM8 co-stimulate proliferation and expansion of B and T cells in vitro.

For diagnostics, soluble CEACAM8 labels neoangiogenetic blood vessels near tumors for cancer diagnosis, with potential drug targeting via CEACAM8 conjugation. The document also describes an apoptosis-screening workflow to identify compounds that prevent apoptosis by binding membrane-anchored CEACAM1 and/or membrane-anchored CEACAM6 in cells expressing membrane-anchored CEACAM8 and CEACAM1/6.

Claims Coverage

The partial content identifies four independent claims covering in vitro B- or T-cell expansion by full-length soluble CEACAM8 (or DNA encoding it), diagnosis, monitoring, or therapeutic treatment of selected patient conditions via immune stimulation and B- or T-cell expansion, apoptosis prevention in human granulocytes by full-length soluble CEACAM8, and therapeutic immune stimulation in a patient via administration of full-length soluble CEACAM8 (or DNA encoding it) to achieve B- or T-cell expansion.

Soluble full-length CEACAM8 contacting for B- or T-cell expansion

Contacting B- or T-cells with full-length soluble CEACAM8 or DNA encoding said full-length soluble CEACAM8 in an effective amount resulting in B- or T-cell expansion.

Administering soluble full-length CEACAM8 for immune stimulation in selected conditions

Administering to a patient full-length soluble CEACAM8 or DNA encoding said full-length soluble CEACAM8 in an effective amount resulting in B- or T-cell expansion, where the condition is chosen from adoptive immunotherapy; immunodeficiency as a result of chronic or acute infection and/or chemo- or radiation therapy; human autoimmune diseases, aberrance of the immune response; human gout, cancer and/or infection diseases.

Full-length soluble CEACAM8 contacting for prevention of apoptosis in human granulocytes

Preventing apoptosis in human granulocytes by contacting the granulocytes with full-length soluble CEACAM8.

Therapeutic immune stimulation via soluble full-length CEACAM8 administration for B- or T-cell expansion

Therapeutically treating a patient requiring immune stimulation by administering to the patient full-length soluble CEACAM8 or DNA encoding soluble CEACAM8 in an effective amount resulting in B- or T-cell expansion.

Across the independent claims, the central coverage is the use of full-length soluble CEACAM8 (or DNA encoding it) to promote B- or T-cell expansion for immune stimulation or therapy, and to prevent apoptosis in human granulocytes, including a patient method that applies these effects to specific categories of diagnosis, monitoring, and therapeutic conditions.

Stated Advantages

Prevents CEACAM8-mAb-induced apoptosis in human granulocytes.

Results in B- or T-cell expansion, with co-stimulation of proliferation/expansion described for in vitro use.

Labels neoangiogenetic blood vessels near tumors for cancer diagnosis.

Supports adoptive immunotherapy and treatment in immunodeficiency as described in the document.

Documented Applications

Immune stimulation therapies involving B- or T-cell expansion, including adoptive immunotherapy and immunodeficiency due to chronic or acute infection and/or chemo- or radiation therapy.

Diagnosis or monitoring of cancer patients by labeling neoangiogenetic blood vessels close to tumors using full-length soluble CEACAM8.

Therapeutic treatment of human autoimmune diseases, aberrance of the immune response, human gout, cancer, and infection diseases as selected condition categories.

Apoptosis prevention in human granulocytes by contacting with full-length soluble CEACAM8, including use in an in vitro granulocyte-containing sample context.

Apoptosis screening to identify compounds that prevent apoptosis by binding membrane-anchored CEACAM1 and/or membrane-anchored CEACAM6 in cells expressing membrane-anchored CEACAM8 and CEACAM1/6.

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