Patent Application
20090060926
1. Field of the Invention
The present invention concerns a medicine for treatment of a carcinoma, in particular prostate cancer.
2. Description of the Prior Art
In the event of inflammation, foreign cells or foreign bodies that have penetrated into the body tissue are attacked and destroyed (primarily by leukocytes) or rendered harmless. In contrast to this, carcinomas have the property that they are not attacked by the immune system of the body, such that in many cases they are only noticed when a successful treatment (for instance against metastasis formation) is barely possible.
An object of the present invention is to provide a medicine that induces the immune system of the body to attack cancer cells.
This object is achieved by a medicine according to the invention that can be supplied via the circulatory system, and thus can be administered intravenously, orally or rectally (for example), and that contains a first active component and a second active component that are coupled with one another. The coupling can ensue, for example, by a direct chemical bond or an indirect association by, for instance, the active components being bound immobilized to a carrier, for instance being enclosed by the carrier or being bound chemically or in another manner to the carrier. The first active component is formed from at least one molecule (designated in the following as a coupling molecule) that specifically binds to the target molecule formed by the cancer tissue. The second active component is formed from at least one signal molecule typical to inflammation, or from at least one originating molecule that can be transformed into such a signal molecule. Due to the coupling molecules of the first active component, the medicine selectively accumulates in the vascular endothelium of the cancer tissue. Due to the signal molecules of the second active component that are typical to inflammation, the cancer tissue presents itself as an inflammation source that is attached by the immune system of the body. As explained in detail below, this leads to a fixation of leukocytes to the signal molecules. A relatively high probability thereby exists that at least a portion of the leukocytes migrate across the vessel wall into the cancer tissue, so the signal or reaction cascades that are specific to inflammation are triggered and at least a portion of the cancer cells are attacked and killed. The medicine according to the invention thus causes a targeted inducement of the self-healing powers of the body.
A cancer tissue 1 (for example a prostate carcinoma) and blood vessel 2 permeating this or directly adjacent to this are respectively indicated in the images. In the exemplary embodiment according to
The coupling molecules 3 are such molecules or molecular structures that bind to target molecules 8 that form in the endothelium 9 of a blood vessel 2. In the preliminary stage of the carcinoma, this has not yet developed blood vessels 2. In this case the target molecules 8 are in the endothelium of blood vessels 2 directly adjacent to the cancer tissue. The CEACAM-1 molecule (carcinoembryonic antigen-related cell adhesion molecule) is formed in the preliminary stage of high-grade intraepithelial neoplasy (for instance of the prostate; hgPIN), for example. Coupling molecules 3 specifically binding to this are, for example, CEACAM-1 antibodies. Carcinomas that have progressed further induce angiogenesis, the formation of blood vessels 2. The growth factors accompanying angiogenesis—such as, for example, VEGF (vasco endothelial growth factor) or Alpha(V)-beta(3)-integrin—thereby serve as target molecules 8 with which corresponding coupling molecules 3 interact as binding partners, for example Alpha(V)-beta(3)-integrin ligands or respective corresponding antibodies in the cited case. So that carcinomas in the preliminary stage and those that are already located in the angiogenesis stage can be detected and treated, the medicine can contain the respective, specifically binding coupling molecules 3 in combination.
Furthermore, molecules known as aptamers are suitable for use as the coupling molecules 3 in the cited cases. These are short, stable and specifically binding RNA chains. Anticalins also are suitable as the coupling molecules 3. These are individual polypeptide chains with approximately 180 amino acids that have specific binding properties similar to antibodies, but are easier to produce.
As already mentioned, the second active component of a medicine according to the invention has the task of pretending to the body's own defense system that cancer tissue is an inflammation source. Corresponding to this goal, the second active component II is formed by at least one signal molecule 4 typical to an inflammation. An inflammation process runs over multiple different stages with which separate signal molecules are respectively associated. However, not all of these signal molecules are suitable for the provided purpose. The attraction and the accumulation of leukocytes in the region of an inflammation source is sub-divided into the phases of tethering, rolling, possible activation, fixed adhesion and transendothelial migration. A separate pair made up of adhesion molecule and leukocyte-persistent ligands binding to said adhesion molecule is responsible for each phase. The initial tethering and the rolling of the leukocytes occurs in that CLA molecules (cutaneous lymphocyte-associated antigen molecules) temporarily bind to E-selectin in the endothelial membrane in the leukocyte membrane. The leukocytes are thereby decelerated from blood stream by a factor of approximately 100. In the next step, leukocytes are activated via chemokines and are thereby put in the position of tethering to VCAM-1 molecules (vascular cytokine activated adhesion molecules) with the use of leukocyte-persistent integrins. An additional adhesion initially ensues. As a result, LFA-1 (leukocyte function antigen) of the leukocytes can tether to ICAM-1 (intercellular cytokine-activated adhesion molecule) in the endothelium, whereby the leukocyte is immobilized. Signal cascades are triggered both in the endothelium and in the leukocytes due to the immobilization, which signal cascades finally cause the migration of the leukocytes into the affected tissue, followed by an inflammation reaction. The binding between VCAM-1 and leukocyte-persistent integrins (for example the alpha-(4)-beta (1) integrin of the skin) followed by the binding between ICAM-1 and leukocyte-persistent LFA-1 represent key processes in many different tissue types. These are therefore particularly suitable to achieve the goal according to the invention, namely to pretend to the immune system that cancer tissue is an inflammation source. Cytokine-activated adhesion molecules (CAM), advantageously VCAM-1 and ICAM-1, are therefore used as inflammation-specific signal molecules 4. In the exemplary embodiment according to
In the exemplary embodiment shown in
In a preferred embodiment of the medicine, the signal molecules 4 are transported to the target tissue not as such but rather in the form of an originating molecule (in particular a plasmid) encoding them. The actual target molecule is only formed at the target location and in fact within an endothelial cell. The introduction of the originating molecule or, respectively, the plasmid into the endothelial cells ensues by transient transfection, which is shown in
Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of their contribution to the art.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2007 041 834.7 | Sep 2007 | DE | national |
