Patent Application
20070191819
The present invention relates to a device, in the following also designated as a medical cell processor or simply a cell processor, which modifies cellular components of human or animal blood, especially cells of the body's natural immune defense, such as, for example, T-cells or macrophages, such that the cells exert a therapeutic effect, for example, against cancerous diseases, e.g., of the liver or the brain, or against other diseases, after their introduction into the human or animal body. Here and in the following sections, the cellular components described are also designated in short as cells. The cells can also involve, for example, other already differentiated, naturally occurring cells of the human or animal body or not-yet differentiated cells, such as stem cells. The cell processor can be implanted into the human or animal body, but non-implantable configurations are also possible. The therapeutic effect of the modified cells introduced into the human or animal body can involve, for example, a controlled active ingredient release or tissue regeneration or the like.
Methods for medical treatment through active ingredients have been known for a long time. In these methods, the active ingredient is usually delivered to the whole human or animal body. The active ingredient can be administered, for example, orally or by injection; it then distributes itself uniformly in the whole human or animal organism. The decisive disadvantage of the previous treatment methods is to be seen in that unaffected regions of the human or animal body can also be affected by the active ingredients and that only a small part of the active ingredient can act in the target regions. Thus, correspondingly high active ingredient doses are unavoidable.
The task of the present invention is to make available a device, for example, a device that can be implanted into the human or animal body and that permits human or animal cells to be modified such that these cells are delivered to targeted, desired body parts or cells after being introduced again into the human or animal body, and there exert a therapeutic effect. By using a device configured in this way it is thus possible, for example, to fight diseases with low dosing in a targeted way or to build up and strengthen tissue in a targeted way, without affecting uninvolved regions of the body.
This problem is solved by a device according to claim 1 and also by a method according to claims 69 and 70. Advantageous improvements of the device according to the invention and also of the described method are described in the dependent claims.
A device or cell processor according to the invention has the following components: a device for isolating cells, for example, from the bloodstream or a blood sample, a cell line or cell culture (for example, freshly isolated cells from patients, primary cultures, etc.), advantageously a device for fixing cells, a device for introducing substances, for example, active ingredients, into the fixed cells or for attaching these substances to the fixed cells, and advantageously also a device for determining the concentration of substances in or on the cells. Advantageously, the device also has a device for introducing cells into the human or animal bloodstream. Advantageously, the cells or the cells and the medium surrounding the cells are transported between the individual devices of the cell processor, for example, with the help of micropumps integrated into or attached to the cell processor. The individual component devices for manipulating the cells are advantageously embodied as devices that are as low contact as possible, because mechanical contact between an immune cell and a surface can trigger an immune reaction.
In one embodiment, the cell processor is implanted in the direct vicinity of an artery (however, the processor can also be arranged or carried outside of the body). The bioprocessor removes blood from the bloodstream. In the chip or the processor, certain blood cells, e.g., leukocytes, are selected and these cells can also be loaded with an unencapsulated medicine. For the use of encapsulated medicines, the capsule can be composed of, e.g., thermally soluble materials, so that by heating in the target region (for example, through hyperthermia therapy), the medicine is released. The encapsulation can also be realized with the help of material that can be split by a cell's own enzymes (for example, dextran). In this case, the medicine is released after a foreseeable time span (equivalent to the use of unencapsulated medicines). For the use of unencapsulated medicines, the carrier cell itself can be destroyed by the medicine after a definable time period. Here, the cell membrane becomes permeable to the medicine. Here, the defined time period can be selected (e.g., by the type of medicine, the medicine's formulation, by the selection of the cytotoxic properties, and/or the concentration), such that the cell can be led to the target location within this time. In this way, the medicine is released in a targeted way at the target location.
The cells are released back into the bloodstream and transport the active ingredient specific to the target to the disease location, e.g., a tumor. The system or the cell processor is thus implanted in the body or carried on the body or arranged outside of the body. For modifying animal or human cells, especially for therapeutic purposes, the cell processor can be applied or used outside of the body, for example, in the laboratory as a laboratory instrument.
If the device is embodied as a device that can be used outside of the human or animal body, then, on one hand, it can be realized as a system that can be carried on the body. However, as described, the device can also be embodied as a laboratory system or as a system to be operated in the laboratory for modifying human or animal cells, for example, for therapeutic purposes. One example is a laboratory system for modifying cells for autologous cancer therapies, in which, for example, immune cells are isolated from the tumor of a patient, then propagated in the laboratory, and finally released back into the bloodstream of the patient. These cells can then be loaded, after the propagation step in the laboratory, with nanoparticles which are coated or provided with medicine and/or nucleic acids and/or other therapeutically active compounds with the device according to the invention. Applications of the laboratory device for screening purposes for pharmaceutically active ingredients are also conceivable.
Thus, the cell processor can be implantable, but can also be provided in a non-implantable form and/or size. The cell treatment, thus, for example, the isolation, fixing, transporting, or counting of cells, etc., however, can also be realized with contact. One example here is cell sorting by means of antibody binding.
The first component device of the cell processor designed according to the invention is the device for isolating the cells. In a first advantageous configuration, this isolating device is composed of at least one capillary, for example, made from a high-polymer plastic, as well as at least two electrodes arranged on this capillary or these capillaries. The cells are led through the capillary, wherein the capillary diameter is designed so that cells can only pass one at a time through the capillary. The individual cell types have different electrical conductivity values. If the cells contact the electrodes then, depending on the cell type, currents of different magnitudes are generated, which can be measured. In this way, the cells are distinguishable from each other and can be selected. An isolating device configured in this way thus isolates the necessary cells from their environment, for example, a blood sample, by comparing the conductivity values of different cell types. In another advantageous embodiment, at least one laser detector is arranged on the capillary or capillaries. Because the different cell types also feature different light-refracting properties, the necessary cells can be selected or isolated with reference to light refraction. In another advantageous embodiment, the necessary cells are isolated by measuring the impedance, in which different cell types also differ. In another advantageous embodiment, a widening is attached at the end at least one of the capillaries, wherein an electromagnetic field is generated on or in this widening, for example, with the help of two electrodes arranged on it. Because different cell types have particle charges with different magnitudes, they are affected by the electromagnetic field to different degrees and accordingly, have a propagation time of different lengths until reaching the capillary wall in the widened area in the electromagnetic field. In this way, the necessary cells can be isolated with the help of their particle charge. In another advantageous configuration of the device for cell isolation, the electrophoretic mobility of the cells is used. This electrophoretic mobility assumes different values depending on the cell properties, such as the density of the surface charge, volume, and weight, and therefore can also be used for selecting the desired cell type. Another advantageous configuration of the device for cell isolation uses the different particle sizes of different cell types. For this purpose, for example, a filter membrane is used which is designed so that only certain blood cells can pass through the membrane, while other blood cells are held back. Here, membrane filters with different pore sizes can also be used. Another possible configuration of the isolating device uses so-called solution diffusion membranes. Mass transfer or isolation of the desired cell type is generated or performed here, for example, using the following means and method: on the primary side of a solution diffusion membrane, a solvent is used which corresponds to all of the contents or all of the present cell types. On the secondary side of the solution diffusion membrane, a solvent is used which is suitable only for one certain component or one certain cell type. In the solvent of the secondary side, thus only the cell type to be isolated is soluble. The component or the corresponding cell type soluble on the secondary side of the solvent membrane has the tendency to diffuse through the membrane, while none of the other components or cell types have this tendency. Thus, the necessary cell type can be isolated. Obviously, other membrane types can be used for cell isolation by means of filtration. The filtration can be realized, for example, in an H-shaped filter module.
As a second component device, the cell processor according to the invention advantageously has a device for fixing the cells. The fixing is used here for holding the cells, so that the substance or the active ingredient can be added to or introduced into the cells. A first advantageous configuration of the component device for cell fixing is composed of a capillary, for example, a high-polymer plastic, a widening at the end of this capillary, and a device inserted into the widening for holding the cells. The device for holding the cells is, for example, a fine needle, to which an electric field is applied. The device uses the particle charges of the cells. However, the maintenance of the particle charge assumes a certain amount of movement of the cells. Therefore, in the present case, an alternating electric field is used, which alternately holds the cells tight and then pushes them away again, so that these remain in motion and the particle charge is thus maintained. The cells to be fixed are thus held by an alternating electric field. Such a component device for fixing the cells with the help of an electric field can be configured, for example, in the form of a three-dimensional microelectrode system for contactless cell manipulation. Such a three-dimensional microelectrode system enables the fixing or the holding of cells in a cage filled with a dielectric liquid. Here, the three-dimensional microelectrode system has, for example, the following components.
Another advantageous configuration of the component device for fixing immune defense cells is configured as follows. With the help, for example, of a fine capillary, gas or a fluid is introduced, for example, into a microball. In this way, the microball is inflated and thus simulates a foreign body. After the defense cell has surrounded the simulated foreign body, thus being fixed, the active ingredient is introduced to the cell. Then the gas or the fluid is released from the microball and the defense cell swims free again. This defense cell fixing through foreign-body simulation thus uses the natural function of defense cells.
A first advantageous configuration of the component device of the cell processor for introducing a substance into the cell or for arranging a substance on the cell, wherein this substance can be an active ingredient, is composed of a device for generating high-voltage pulses, for example, with the help of microelectrodes which have been coated, for example, through sputtering of gold. With the help of such high-voltage pulses, which can be realized, for example, in the form of a step-shaped potential, small reversible pores are formed in the cell membrane. Then the corresponding substances or active ingredients are introduced into the cells through these pores. In the present configuration, the active ingredient or the substance is thus introduced by means of electroporation. This also applies for all of the methods presented below for introducing a substance into the cells or for arranging a substance on the cells. The surface of the substances or active ingredients can be modified so that the substances or the active ingredients are no longer recognized by the cells.
Another advantageous configuration of the component device for introducing or arranging substances or active ingredients uses magnetizable or magnetized nanoparticles or small spherules, which are coated with or contain the substance or the active ingredient. Here, nanoparticles are usually particles with a size of a few nanometers up to a few hundred nanometers. However, below, particles with a size, for example, in the micrometer range are also to be understood as nanometers. The component device now contains a device for generating a magnetic field. This can contain or be composed of, for example, at least one microcoil. The particles or spherules are set in motion or vibration with the help of this magnetic field, which here advantageously concerns an oscillating field, but static fields are also possible, and therefore tends to penetrate into the cell at a sufficient field strength of the magnetic field. The oscillating field can be, for example, sinusoidal-shaped or sawtooth-shaped. If the particles or spherules are found in simple liquids, then preferably static magnetic fields are used. If they are found in more complex biological media, then preferably oscillating fields are used. An advantageous configuration of the magnetic field-based introduction device here has a reservoir which is filled with the corresponding nanoparticles or spherules. A capillary with a lock is attached to the reservoir, wherein the lock always lets pass only a precisely defined number of nanoparticles or spherules. A magnet is mounted underneath the capillary. The cell to be modified is fixed between the magnet and the capillary. The substances or active ingredients are added to the corresponding nanoparticles or spherules. These are optionally still magnetized before or after. If the magnet in this arrangement is activated, then the nanoparticles or spherules are pulled into the cell. The decisive factors are the time and the strength of the magnetic field: the nanoparticles or spherules may not completely pass through the cell, they must remain in it. The nanoparticles or spherules can be, for example, particles containing Fe2O3 or Fe3O4 or paramagnetic particles. The cells loaded with the nanoparticles using the described means and methods can also be used for diagnostic purposes (comparable to the application of contrast means). The nanoparticles can also be coated with contrast means or similar materials of high atomic number. The cells loaded with nanoparticles can then also help through the physical properties of the nanoparticles, such as, for example, magnetic characteristics (magnetized nanoparticles), for disease identification or better recognizability of diseases. The cells loaded with nanoparticles can also be used for diagnoses and simultaneously for medication. This is then possible through the magnetic properties of the nanoparticles and their simultaneous coating with an active ingredient.
In another advantageous configuration of the component device for introducing substances or active ingredients into the cells, liposomes are used. Liposomes have the ability to penetrate the cell membrane of a cell, thus with their help a substance or an active ingredient can be transmitted into the cell. The substance or the active ingredient is thus first introduced into a liposome. This is realized advantageously as previously described via active ingredient-coated, magnetized particles. Then the substance or the active ingredient is transmitted into the cell by means of lipofection, i.e., the liposome complex fuses with the cell membrane and discharges the substance or the active ingredient into the cell. In another advantageous configuration of the component device of the cell processor for introducing a substance or an active ingredient into the cell, phagocytosis is used. Phagocytes are cells that ingest other cells. They engulf foreign matter and dissolve and destroy it by means of enzymes. Thus, the natural function of immune cells is used, in that the active ingredient or the substance is recognized as a foreign body and surrounded by an immune cell. For this purpose, the substance or the active ingredient is added in a form that makes it indigestible for the immune cell. In another advantageous configuration of the component device for introducing substances or active ingredients into the cell, viruses are used. These viruses can involve, for example, modified HIV viruses. Alternatively, DNA which triggers the cell itself to produce a desired active ingredient or a desired substance can be introduced into the cell. In a last example configuration of a component device for introducing substances or active ingredients into a cell, a very fine needle is used for microinjection. The substance or the active ingredient is injected with the help of this very fine needle through a very fine hole in the fixed cell. Instead of the needle, nanofibers made from, for example, carbon compounds can also be used for injection. Here, the nanofibers advantageously have a diameter at the tip of a few tens of nanometers. If these fibers are arranged with a distance from each other corresponding to the cell size, for example, on a silicon chip in a two-dimensional matrix, cells deposited on the chip, for example, with the help of centrifugal forces, are pierced by only one fiber, wherein a substance or an active ingredient can be injected into the cell.
A first advantageous configuration of a component device for determining the concentration of a substance or an active ingredient in or on the cell uses at least one sensor for determining magnetic field strengths. With the help of such a magnetic field sensor, upon the use of magnetized nanoparticles or spherules, the substance or the active ingredient concentration is measured in the cell by measuring the magnetic field strength of the nanoparticles or spherules. The sensitivity of the sensor is here configured advantageously according to the minimum substance or active ingredient charging, the measurement resolution according to a substance or active ingredient charge unit. In the case of the use of magnetized particles in liposomes, the sensor can also be used, for example, to determine the number of particles loaded into a liposome. In an embodiment, the magnetic field sensor contains a Hall sensor or a two-dimensional array of Hall sensor elements comprising, for example, 4×4=16 individual Hall elements. In another embodiment, the sensor involves a magnetoresistive sensor or an arrangement of microcoils which detect the magnetic fields inductively. The magnetic field sensors here work contact-free, i.e., the substance or the active ingredient concentration is determined without contacting the substance or the active ingredient coupled to the magnetic materials or the cells. In another advantageous configuration, the active ingredient or substance concentration is determined with the help of a device for measuring the fluorescent light from fluorescing pigments and/or with the help of biomarkers. For this purpose, a fluorescing substance or a marker substance is applied to the substance or to the active ingredient. In another advantageous configuration, the cell processor has a device for determining the number or for controlling the number of modified cells.
In an advantageous configuration of the cell processor according to the invention, the component device for determining the concentration of a substance or an active ingredient in or on the cell and the component device for introducing substances or active ingredients into the cell are housed in a common reaction chamber. Advantageously, this reaction chamber has at least two feed devices, such as, for example, microchannels: one feed device for feeding the cells and one feed device for feeding substances or active ingredients, optionally also washing reagents. The washing reagents are fed after the active ingredient treatment. Advantageously, the reaction chamber has other elements for the electrophoresis, such as, for example, funnel-shaped or shaft-shaped microelectrodes for aligning electrostatically charged cells or straight or zigzag-shaped microelectrodes for deflecting electrostatically charged cells.
However, the component device for determining the concentration of a substance or an active ingredient and the component device for introducing substances or active ingredients into the cell can also be arranged in different compartments (for example, a chip with different reaction chambers or compartments, so that the concentration is determined and the active ingredient is introduced in different areas of the chip). Compartments or reaction chambers are areas of the device which are separated from each other (for example, through suitable wall structures) and which can represent or integrate different functional units of the device (for example, mixing chamber, electroporation unit or separation unit). The individual compartments or reaction chambers can then be connected to each other via suitable flow channels so that the cells can be led from one compartment or reaction chamber to another.
In another advantageous configuration, the cell processor has a component device for introducing the cells into the human or animal bloodstream. This can contain, for example, micropumps, microvalves, micronozzles, and/or microfilters for controlling the flow of a fluid containing cells. If the modified cells are introduced into the human or animal body, they are then transported to a desired, defined tissue type via the bloodstream. The desired, defined tissue is reached by the ability of cells to track down this tissue with the help of messenger materials which are screened by the desired tissue. Analogously, it is also possible to discover previously unknown diseased tissue.
In another advantageous configuration, the cell processor according to the invention is equipped with a device for discharging substances or active ingredients to a defined human or animal tissue. Such a device is, for example, a device for generating an electromagnetic field which is applied in the use of magnetized nanoparticles. Here, the nanoparticles are pulled from the immune cell by a magnetic field applied with the help of the device. However, the discharge of the substance can be realized not only with the help of a magnetic field generated by the implantable microcell processor, but also by a magnetic field generated outside or minimally invasively within the body. Thus, the substance or the active ingredient is discharged as desired locally to the tissue. Analogous to the loading of the cells, here static and/or oscillating magnetic fields come into question. Through suitable selection of the field form and strength, the active ingredient can be fed to the desired tissue in a controlled way and thus ideally dosed. In another embodiment, the device for discharging substances or active ingredients is a device for destroying modified cells at the location of the desired tissue. Such a device can be, for example, a chemical to which the substance or the active ingredient dissolving the cell at the desired tissue was added. Triggers of the self-destruction can be, for example, the concentration of messenger materials, which are segregated by the desired tissue. Another possible configuration of the device for discharging substances or active ingredients is a device for generating ultrasound fields with a field strength sufficient for destroying the cells. The ultrasound field for discharging the substance can be generated not only as described by the implantable microprocessor itself, but the substance can also be discharged by an ultrasound field generated outside of the body or minimally invasively within the body.
Another advantageous configuration of the cell processor according to the invention is equipped with a device for localizing modified cells, for example, in the human body. The device for localizing can be, for example, a sensor for detecting a magnetic field generated by modified cells or a detecting device for biomarkers or a detecting device for fluorescent light.
Another advantageous configuration of the cell processor according to the invention concerns the integration or the arrangement of a rechargeable battery for supplying power. If the cell processor is used outside of the body, then advantageously a conventional rechargeable battery power supply can be fallen back upon. If the cell processor is used within the body, it is advantageous to use a long-service-life rechargeable battery, like those also used, for example, in cardiac pacemakers (lithium-ion rechargeable batteries). Such a long-service-life rechargeable battery can be exchanged through a minimally invasive operation. In another advantageous embodiment, the cell processor according to the invention is equipped with a contactless, inductive power supply. Here, for example, at the location of the implanted cell processor, a first coil with a rectifier is inserted, which powers a rechargeable battery or a capacitor, such as a SCAP [switched capacitor analysis program], which, in turn, represents the power supply for the cell processor. A SCAP is a high-power double-layer capacitor wherein the electrical energy is stored by charge shifting at the boundary between the electrode—usually made from carbon—and the organic electrolytes. The capacitor or the rechargeable battery is charged inductively via the first coil by a second coil which is applied to the body surface and to which an alternating field is applied. This outer second coil can be fixed, for example by a band on the body, in the sleeping phase. In another possibility for the configuration of the cell processor according to the invention, power is supplied through the use of special carbon nanotubes. These carbon nanotubes generate an electric charge when carrying a flow of a fluid, for example, blood. Thus, the necessary energy is provided by the fluid flow.
In another advantageous embodiment of the cell processor, there is at least one reservoir on or attached to the cell processor. Such a reservoir is used for storing at least one substance or active ingredient. The substances or active ingredients can be, for example, therapeutic agents, such as medicines, medicine precursors (prodrugs), hormones, enzymes for cleaning medicine precursors, viruses which are used, for example, for gene therapy, or nanoparticles. If the reservoirs are emptied in the case of an implanted cell processor, they can be refilled, for example, from the outside through a minimally invasive operation, e.g., with a fine needle. The filling can be realized by various kinds of septa. Another advantageous configuration of the cell processor according to the invention concerns the integration of a so-called home monitoring system, which reports, with a transmitter, the necessity for applying a substance or active ingredient.
In one advantageous embodiment, the cell processor or parts of the cell processor according to the invention are composed of biocompatible material and/or different types of metal, such as, silver, titanium, or V2A, and/or ceramic and/or plastics, such as polyethylene, silicon, polymer 908. Here, the surface of the cell processor is advantageously modified such that it is not identified by the immune system as a foreign body, or the cell processor secretes substances which suppress local defense reactions of the body (e.g., steroids).
The cell processor described above for modifying cells distinguishes itself through a series of considerable advantages. It allows the targeted transport of active ingredients of a wide variety with the help of the body's natural immune defense, such as T-lymphocytes, monocytes, or neutrophils (the latter after stimulation, for example, with β-glucan; see Hong et al., 2003, Cancer Research 63; 9023-9031) or other blood cells. In this way, the blood cells are held by the cell processor and substances, active ingredients, or therapeutic means such as medicines, medicine precursors (prodrugs), hormones, enzymes for cleaving the medicine precursors, viruses that are used, e.g., for gene therapy, or nanoparticles are transmitted to these cells. The defense cells modified in this way are then fed back into the human or animal bloodstream. The body's natural immune defense has the natural ability to recognize certain tissues. Through targeted treatment measures, a tissue can also be made recognizable to the immune system, i.e., target immune cells can be directed to a certain tissue and the recognition of this target tissue can be reinforced by immune cells.
One example is the targeted heating of a tumor, e.g., through hyperthermia or thermotherapy.
In this way, so-called heat shock proteins are produced in the heated tissue, such as, for example, HSP 96, HSP 72. These can play a role in the complex process leading to the antigen presentation at the cell surface. Furthermore, they can also be discharged in the extracellular environment and used for the immune system as signs for abnormal, dead, or damaged cells. An immune response in this tissue is reinforced.
An immune therapy with specific or multi-tumor-specific epitopes represents another example, or induction of the immune response through infiltration of cells or effector cells presenting corresponding antigens in the immune system, which also increase the reinforcement of the immune system in the tumor tissue. In addition, DNA vaccination is also conceivable in addition to the administration of protein antigens.
By reinforcing the immune response in the target tissue through prior treatment, e.g., heating before or during the use of the biocell processor or cell processor, the medicine transport also becomes more specific and more effective through loaded immune cells.
Immunization with the preparation of heat shock proteins (HPS) which are directed toward cancer cells was described as a stimulating factor for the immune system with regard to cancer identification (Blanchere et al. 1997).
Thus with the modified cells, with the help of the natural ability of the body's natural immune defense, certain tissue can be controlled in a targeted way and the active ingredient can be discharged at the desired position. The type of transmission of the active ingredient on the transport medium with the help of the cell processor according to the invention can vary as described. Both an addition (adsorption) of the active ingredient on the surface and also a storage (absorption) in the transport medium are possible. Also, the type of active ingredient addition can vary as described. Among other things, mechanisms such as electroporation, lipofection, or microinjection are possible. The cell processor according to the invention can transmit the active ingredients to the transport medium both within the body and outside of the body.
The transport of the medicine or the other components through the immune cells can be realized such that the material to be transported is stored in the immune cell or in another membrane, such as, e.g., a liposome, or is coupled to its surface (in the latter case, the material is not stored directly in the cell, but instead encapsulated in the other membrane, stored in the cell, or introduced into the cell added to the surface of this membrane.
The therapy according to the invention can be combined with all other therapies such as, e.g., cancer vaccination, reinforcement of the body's natural immune defense through, e.g., cytokine production, etc. The combination of therapies can be realized independent of each other, but they can also happen in parallel, before, or after the other therapies.
It is also conceivable that the therapy according to the invention is connected to other therapies, such that, e.g., through the reinforcement of the body's natural immune defense or cancer vaccinations, the cells necessary for the desired purpose are first increased and then separated out of the bloodstream for the therapy according to the invention.
In the therapy according to the invention, with the help of the body's natural immune defense, medicines coupled with an antibody which recognizes the cell to be treated can also be transported.
An antibody which docks the defense cell to the cell to be treated in a targeted way can be coupled to the body's natural defense cell.
With the help of the defense cell, in addition to medicines, all other materials, such as, e.g., nanoparticles, viruses, liposomes, proteins, nucleic acids, amino acids, hormones, radioactive particles, antibodies, antigens, peptides, all types of chemicals, etc., can also be transported.
As an example application, e.g., synthetic or natural hereditary information, e.g., RNA (e.g., siRNA) or DNA can be transported, which is linked to the cell to be treated or to its hereditary information, whereby the cell, e.g., is made harmless, further growth or cell division is prevented, or else is made more recognizable for the immune system and therefore cells of the immune system are directed in a targeted way to the treated cells (for example, cancer cells).
Cell processors according to the invention for modifying human or animal cells can be configured as described in one of the following examples.
In the figures described below, the same reference symbols are used for the same or corresponding components or parts of the cell processor.
Therefore, the cell itself is also protected from the effect of the medicine.
The capsule or formulation has properties through which it is triggered at the target location, e.g., through external heat supply at the target or through triggering of certain physiological conditions.
Therefore, the medicine displays the effect only at the target location. The medicine can also represent a precursor (prodrug), which transitions into the active form only at the target location.
| Number | Date | Country | Kind |
|---|---|---|---|
| 103 39 905.4 | Aug 2003 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP04/09414 | 8/23/2004 | WO | 9/11/2006 |
