Personalized autologous cancer vaccines and oncology dialysis systems and methods for blood purification

Abstract

A system and method for preparing a cancer vaccine (and optionally purifying blood) comprises a hemofiltration system controlled by a control unit for filtering exogenous plasma to isolate tumor cells, tumor stem cells, and tumor degradation products. The hemofiltration system filter may include multiple layers with openings of different sizes to hold substances of different sizes (from among tumor cells, tumor stem cells, and tumor degradation products of different sizes). The apparatus directs electromagnetic radiation to the isolated tumor cells, tumor stem cells, and / or tumor degradation products, which can cause a coagulated outer layer by degrading the outer surface of the isolated tumor cells, isolated tumor stem cells, and / or isolated tumor degradation products (e.g., tumor proteins such as DNA and / or tumor exosomes). The electromagnetic radiation may have a UV wavelength. A conical coil improves flow uniformity. Tumor exosomes can be centrifuged.

Description

Technical Field

[0001] Embodiments described herein generally relate to systems and methods for purifying cancerous elements from the blood of a mammalian subject and / or tumor dialysis systems or methods. More particularly, tumor cells, tumor stem cells and / or their tumor degradation products (components) are separated from the exogenous blood or other body fluids of a subject, and these tumor cells, tumor stem cells and / or tumor degradation products are modified (reprogrammed) to produce a customized cancer vaccine for the subject, which can then be injected or delivered to the subject.

Background Art

[0002] Generally, significant progress has been made against cancer diseases, but cancer remains a formidable disease. Moreover, some treatments (e.g., chemotherapy) cause harmful side effects. Furthermore, chemotherapy typically does not show a high success rate for advanced stages (e.g., stage 4 cancer patients).

[0003] In some approaches to fighting cancer, tumor cells from a patient are injected into an animal such as a mouse to cause the mouse to produce antibodies (e.g., monoclonal antibodies) against these tumor cells, and then the antibodies are injected into the patient. This approach causes undesirable side effects, such as an allergic reaction in which the patient's immune system recognizes the antibodies as foreign (since mouse antibodies contain foreign animal proteins and are not necessarily compatible with the patient's body's immune system). In addition to autoimmune disorders or autism side effects, the level of affinity is not sufficient to reliably induce an immune response necessary to successfully attack cancer tumors.

[0004] Efforts have been made to modify or humanize these animal antibodies by making their protein sequences more similar to those produced in humans, often by individuals with the same type of cancer. For example, humanization of mouse monoclonal antibodies is performed by substituting the mouse constant region and V-framework region for human sequences.

[0005] However, while this represents a significant improvement over mouse antibodies in terms of in vivo tolerability, it is recognized that "even some humanized and fully human sequence-derived antibody molecules still pose immunological risks." ("The immunogenicity of humanized and fully human antibodies," MAbs, 2010, May-June;2(3):256-265 at Abstract (https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC2881252 / #:~:text=Humanization%20of%20murine%20monoclonal%20antibodies,a%20significantly%20less%20immunogenic%20product)) [Overview of the project]

[0006] (Summary of the embodiment) One embodiment is a system for preparing an autologous cancer vaccine for a mammalian subject using components of the subject's own exogenous blood without using surgically invasive biopsy of the subject. This system is A hemofiltration system for filtering autologous exogenous plasma to remove neoplastic components from autologous exogenous plasma, wherein the neoplastic components include at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products, and the neoplastic components are not recognized as antigens by the subject's immune system. A coil, having a base at its widest point and located upstream of a hemofiltration system, is arranged or formed in a conical shape, wherein the base is configured to receive peristally flowing exogenous plasma, and the coil is configured to increase the uniformity of the flow rate of the exogenous plasma output to the hemofiltration system, thereby inhibiting hemolysis of the exogenous plasma. The device includes at least one apparatus for making the tumor components removed by the subject's immune system recognizable as antigens by directing electromagnetic radiation having a UV wavelength to the removed tumor components in order to convert the outer surface of at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products into a coagulated outer layer, and a processing unit configured to control the blood filtration system.

[0007] In some embodiments, the hemofiltration system is configured to filter autologous exogenous plasma output from coils arranged or formed in a cone shape to remove multiple types of neoplastic components. The multiple types include at least two of tumor cells, tumor stem cells, and tumor degradation products. None of the multiple types of neoplastic components are recognized as antigens by the subject's immune system. The at least one device is configured to convert each of the at least two of the multiple types of removed neoplastic components into antigens by directing electromagnetic radiation to each of them. This results in each of the at least two of the removed tumor cells, tumor stem cells, and tumor degradation products having a coagulated outer surface that is recognizable as an antigen by the immune system.

[0008] In some embodiments, the oncogenetic component includes tumor degradation products, and the tumor degradation products include tumor exosomal peptides.

[0009] In some embodiments, at least one apparatus further includes a device for directing electromagnetic radiation to at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products to generate a coagulated outer layer. The electromagnetic radiation has a terahertz frequency up to 0.1 terahertz.

[0010] In some embodiments, a cone-shaped arrangement or cone-shaped coil is located upstream of the hemofiltration system, further comprising a peristaltic pump upstream of the cone-shaped arrangement or cone-shaped coil, and the cone-shaped arrangement or cone-shaped coil is configured to receive exogenous plasma flowing from the peristaltic pump.

[0011] In some embodiments, the system further comprises (i) a peristaltic pump downstream of the hemofiltration system, and (ii) a cone-shaped or cone-shaped additional coil located downstream of the hemofiltration system, with its base at its widest point. The additional coil is configured to receive the exogenous plasma flowing from the pump and inhibit hemolysis of the exogenous plasma output from the peristaltic pump by increasing the uniformity of the flow velocity of the exogenous plasma output from the peristaltic pump.

[0012] In some embodiments, the filter has multiple layers, each layer having openings of different sizes to hold material of different sizes from (i) one or more sizes of tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products. In some embodiments, the filter has an outer layer and a second layer. The outer layer is configured to hold tumor cells and has openings of a first diameter. The second layer is configured to hold tumor stem cells and has openings of a second diameter smaller than the first diameter. In some embodiments, the filter further comprises an inner layer. The inner layer is configured to hold tumor degradation products and has openings of a third diameter smaller than the second diameter. In some embodiments, the layers of the filter include an outermost layer having openings configured to hold the largest size tumor cells, an inner layer (a layer inside the outermost layer) having openings configured to hold the second largest size tumor cells, an intermediate layer having openings configured to hold tumor stem cells, and an additional layer having openings configured to hold tumor degradation products.

[0013] In some embodiments, the blood filtration system includes an actuator configured to rotate the filter back and forth across a defined sector.

[0014] In some embodiments, the hemofiltration system is also configured to filter the subject's exogenous blood to isolate exogenous plasma.

[0015] In some embodiments, the system further comprises removed tumor components, the removed tumor components comprising two or more of (i) removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products.

[0016] In some embodiments, the system further comprises the removed tumor components, which include (i) removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products.

[0017] In some embodiments, at least one apparatus includes an apparatus configured to direct UVA irradiation, an apparatus configured to direct UVB irradiation, and an apparatus configured to direct UVC irradiation to one or more of (i) removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products.

[0018] In some embodiments, the removed tumorous component consists only of the plasma residue, which is less than about 5% by volume of the separated tumorous component.

[0019] In some embodiments, the removed tumorous component consists only of the plasma residue, which is less than about 1 volume percent of the separated tumorous component.

[0020] In some embodiments, the removed tumorous component consists only of the plasma residue, which is less than about 0.5 volume percent of the separated tumorous component.

[0021] In some embodiments, the removed tumorous component consists only of the plasma residue, which is less than about 0.1 volume percent of the separated tumorous component.

[0022] In some embodiments, the removed tumorous components include at least two of (i) removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products.

[0023] In some embodiments, the removed tumorous components include (i) removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products.

[0024] In some embodiments, the system further comprises the removed oncogenetic component, the removed oncogenetic component comprising the removed oncolytic product, and the removed oncolytic product comprising the tumor exosomal peptide.

[0025] Another embodiment is a method of preparing an autologous vaccine against cancer in a mammalian subject using components of the subject's autologous blood and without using a surgically invasive biopsy of the subject. This method includes positioning a coil disposed in a conical shape or formed in a conical shape upstream of a blood filtration system. The base of the conical coil is disposed at the widest part of the coil and is configured to receive the peristaltically flowing autologous plasma of the subject. The coil is configured to increase the uniformity of the flow rate of the exogenous plasma output to the blood filtration system, thereby inhibiting hemolysis of the exogenous plasma.

[0026] The method further includes filtering, by a blood filtration system, autologous exogenous plasma output from a coil disposed in a conical shape or formed in a conical shape to remove a tumorous component including at least one of tumor cells, tumor stem cells, and tumor degradation products, the tumorous component not being recognized as an antigen by the immune system of the subject; and converting the removed tumorous component into an antigen by directing electromagnetic radiation to the removed tumorous component, such that each of at least one of the removed tumor cells, tumor stem cells, and tumor degradation products has a coagulated outer surface. Thereby, the removed tumorous component is modified to be recognizable as an antigen by the immune system.

[0027] In some embodiments, the method further includes filtering, by a hemofiltration system, autologous heterologous plasma output from a coil arranged in a conical shape or formed in a conical shape to remove multiple types of tumorous components. The multiple types include at least two of tumor cells, tumor stem cells, and tumor breakdown products, and do not include any of multiple types of tumorous components recognized as antigens by the immune system of the subject. The method further includes converting, by guiding electromagnetic radiation to at least two types of the removed tumorous components, each of the at least two types of the removed tumorous components into an antigen. Thereby, each of at least two of the removed tumor cells, tumor stem cells, and tumor breakdown products has a coagulated outer surface recognized as an antigen by the immune system.

[0028] In some embodiments, the method further includes using a peristaltic pump located upstream of a coil arranged in a conical shape or formed in a conical shape. The coil arranged in a conical shape or formed in a conical shape is arranged upstream of the hemofiltration system and is configured to receive exogenous plasma flowing from the peristaltic pump.

[0029] In some embodiments, the method further includes arranging a peristaltic pump downstream of the hemofiltration system and using an additional coil arranged or formed in a conical shape downstream of the pump. The additional coil has a base at its widest part, is configured to receive exogenous plasma flowing from the pump, and increase the uniformity of the flow rate of the exogenous plasma output from the pump, thereby inhibiting its hemolysis.

[0030] In some embodiments, the electromagnetic radiation has a wavelength in the ultraviolet (UV) range.

[0031] In some embodiments, the UV irradiation includes at least two of UVA irradiation, UVB irradiation, and UVC irradiation, and the UVA, UVB, and UVC irradiations are each applied separately.

[0032] In some embodiments, UV irradiation includes UVA irradiation, UVB irradiation, and UVC irradiation, each of which is applied separately.

[0033] In some embodiments, the method further includes irradiating at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products with electromagnetic radiation up to 0.1 terahertz.

[0034] In some embodiments, the method further includes applying hydrogenated water having a pH of about 8 to about 10 and a redox potential of about -400 to -800 mV to at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products.

[0035] In some embodiments, the method further includes the step of freezing at least one of the removed tumor cells, removed tumor stem cells, or removed tumor degradation products for at least 5 minutes.

[0036] In some embodiments, the method further includes injecting a subject with at least one of irradiated tumor cells, irradiated tumor stem cells, and irradiated tumor degradation products to cause the subject's immune system to produce antibodies in response to a coagulated outer surface.

[0037] In some embodiments, the method further comprises filtering plasma using a hemofiltration system comprising a multilayer rotatable filter, each layer of the multilayer rotatable filter configured for tumor cells or tumor degradation products of different sizes. In some embodiments, the rotatable filter has an outer layer configured to hold tumor cells and having an opening of a first diameter, and a second layer configured to hold tumor stem cells and having an opening of a second diameter smaller than the first diameter. In some embodiments, the rotatable filter further comprises an inner layer configured to hold tumor degradation products and having an opening of a third diameter smaller than the second diameter. In some embodiments, the rotatable filter includes an outermost layer having an opening configured to hold the largest size tumor cells, an inner layer (a layer inside the outermost layer) having an opening configured to hold the second largest size tumor cells, an intermediate layer having an opening configured to hold tumor stem cells, and an additional layer having an opening configured to hold tumor degradation products.

[0038] In some embodiments, the oncogenetic component comprises at least two of tumor cells, tumor stem cells, and tumor degradation products. In some embodiments, the oncogenetic component comprises tumor degradation products, the tumor degradation products comprising tumor exosomal peptides. [Brief explanation of the drawing]

[0039] The specification describes various embodiments as examples, with reference to the attached drawings. [Figure 1] Figure 1 is a schematic diagram of a tumor dialysis system according to one embodiment. [Figure 2] Figure 2 is a schematic diagram illustrating the effect of electromagnetic radiation on the outer layer of tumor degradation products, such as isolated tumor cells, isolated tumor stem cells, and isolated DNA, used in one embodiment of the system and method. [Figure 3A] Figure 3A shows the outer layer of a multilayer filter in a blood filtration system according to one embodiment. [Figure 3B]Figure 3B shows the outermost intermediate layer of a multilayer filter in a blood filtration system according to one embodiment. [Figure 3C] Figure 3C shows another intermediate layer of a multilayer filter in a blood filtration system according to one embodiment. [Figure 3D] Figure 3D shows the inner layer of a multilayer filter in a blood filtration system according to one embodiment. [Figure 3E] Figure 3E is a schematic diagram of a centrifuge in a hemofiltration system according to one embodiment, in which the exosome fraction is separated from plasma and reprogrammed using electromagnetic radiation. [Figure 4] Figure 4 is a schematic diagram of another version of the system according to one embodiment. [Figure 5] Figure 5 is a schematic diagram of various devices used to reprogram tumor cells, tumor stem cells, and the degradation products of tumor cells and tumor stem cells. [Figure 6] Figure 6 is a flowchart showing a method according to one embodiment. [Figure 7] Figure 7 is a flowchart showing another method according to one embodiment. [Figure 8] Figure 8 is a flowchart showing another method according to one embodiment. [Modes for carrying out the invention]

[0040] (Detailed explanation of the example) The following detailed description represents the best currently conceivable mode for carrying out the present invention. The description is not to be constrained, and the scope of the invention is best defined by the appended claims; therefore, it is provided merely to illustrate the general principles of the invention.

[0041] The applicant understood that even antibodies such as monoclonal antibodies, which are humanized by incorporating protein sequences found in human antibodies of people with the exact same type of cancer, may not be a good match for a patient because even certain types of cancer (e.g., glioblastoma) exhibit variability from person to person. Therefore, antibodies produced by other people have insufficient affinity.

[0042] Therefore, the applicant employs a completely different approach, namely, an approach to produce an individualized and customized tailor-made vaccine. This approach, in one embodiment, includes collecting the patient's blood containing circulating tumor cells, tumor stem cells, and tumor degradation products (DNA, protoplasm, etc.) of these tumor cells and tumor stem cells circulating in the bloodstream, isolating them, and reprogramming them, for example, outside the body, so that when reinjected into the patient / subject, the patient's immune system recognizes them as foreign and the patient produces antibodies against the “exogenous” reprogrammed tumor cells, tumor stem cells, and / or tumor cell degradation products. Thus, in one embodiment, a vaccine that is strictly customized for the patient is produced. Furthermore, in some embodiments, the patient's blood is purified, as circulating tumor cells, tumor stem cells, tumor DNA, and other degradation products are removed. Thus, the purified blood is adapted to be recirculated into the patient's veins, and as a result from the purification process alone, the risk of metastasis in the patient is much lower.

[0043] One embodiment generally provides a system and method for preparing a cancer vaccine for a mammalian subject using tumor dialysis. When a tumor metastasizes, cells from the tumor migrate into the patient's blood (and to certain nearby lymph nodes). In the preparation of the system and method (or according to some embodiments of the present method), blood containing circulating tumor cells and circulating tumor stem cells is removed from the patient's blood, for example, about 40 cc at a time, or in other embodiments, about 200 cc at a time, for example, using a peristaltic pump connected by a tube to the patient's vein (i.e., one arm of the patient), or by another method. The peristaltic pump may include a mechanism for inducing blood circulation. In one embodiment, since the movement of blood is not uniform and is driven by pulsation by the peristaltic pump, a damper, for example, at least one cone-shaped coil arranged or formed downstream of the pump, is used to maintain a smooth flow of blood (by increasing the uniformity of blood flow velocity). After passing through a coil or damper, the exogenous blood may continue into a container, such as a blood reservoir, from which, in some embodiments, it moves into a hemofiltration system through the inlet of the hemofiltration system. The exogenous blood referred to herein is autologous.

[0044] The hemofiltration system is configured to isolate or separate at least one (or, in other embodiments, at least two or all three) of tumor cells, tumor stem cells, and tumor degradation products from exogenous plasma (the exogenous plasma itself filtered from the subject's exogenous blood) using, for example, a filter which may have multiple layers. In some embodiments, the system is also configured to isolate plasma from the subject's exogenous blood as a preliminary step.

[0045] Part of the filtration process may also include subjecting the filtered material, such as cells, to evaluation to determine whether or not they are tumor cells. Such treatment may include staining cells that are too large to pass through a particular layer of the filter, and then observing these cells under a microscope to determine whether or not they are actually cancerous. In some embodiments, this tumor identification step is automated. In some embodiments, this tumor identification step is performed by a human operator or physician.

[0046] After filtration in the blood filtration system, at least one of the isolated tumor degradation products, such as isolated tumor cells, isolated tumor stem cells, tumor proteins (i.e., tumor proteins, tumor peptides, tumor exosomal peptides, tumor DNA, or tumor RNA fragments, or other fragments that were inside tumor cells), is reprogrammed. This can, but is not limited to, occur within a vessel.

[0047] As part of the reprogramming process, these isolated or separated products (products) may be exposed to electromagnetic radiation, such as UV wavelength electromagnetic radiation, for about 5 to 9 seconds (or for an amount in between). Other treatments, such as hydrous water, ozone, or freezing, may be used in the reprogramming step. These reprogrammed and isolated components are then adapted to be injected into the patient's muscle (or otherwise delivered). The purified blood is adapted to be recirculated or reintroduced to the patient, for example, through a vein in the patient's arm (different from the arm from which the blood was initially drawn). In some embodiments, recirculation occurs after the purified blood has been passed through a further peristaltic pump and at least one further cone-shaped coil.

[0048] During reprogramming, electromagnetic radiation coagulates the outer layer of one or more isolated components (tumor cells, tumor stem cells, and tumor cell degradation products such as tumor DNA and tumor protoplasm). Furthermore, in some embodiments, all (or virtually all) of the circulating (metastatic) tumor cells and circulating tumor stem cells, as well as their respective components, are removed from the blood itself.

[0049] Reprogrammed components circulating in the patient's bloodstream, possessing a coagulated outer layer, are recognized by the patient's immune system as foreign substances or foreign proteins, i.e., antigens, because the patient's immune system does not recognize these coagulated outer layers as the outer surface of any protein or cell recognized from the patient's body. Consequently, the patient's immune system is induced to produce autoantibodies that attack the reprogrammed tumor cells, reprogrammed tumor stem cells, and / or reprogrammed tumor cell degradation products (e.g., reprogrammed tumor proteins, tumor peptides, tumor exosomal peptides, or tumor DNA (these are not limited examples of tumor degradation products)).

[0050] As used herein, “tumor degradation products” (and the term “tumor cell degradation products”) refers to one or more components of tumor cells or tumor stem cells that have been degraded from tumor cells or tumor stem cells. Examples include tumor DNA, tumor protoplasm, tumor proteins, tumor peptides, and other degradation products of tumor cells or tumor stem cells. As used herein, “tumor cell degradation products” refers to tumor degradation products derived from tumor cells. As used herein, “tumor stem cell degradation products” refers to tumor degradation products derived from tumor stem cells. As used herein, “reprogrammed tumor degradation products” means one or more tumor degradation products that have been reprogrammed in relation to their external surface by one or more methods described herein (e.g., application of electromagnetic waves).

[0051] In this application, the word "isolated" means separated, and the phrase "to isolate" means to separate. Therefore, what is described as "isolated" (separated) in this specification does not necessarily exist in isolation.

[0052] Examples of tumor proteins, which are also examples of tumor peptides, include the exosomes of tumor cells and tumor stem cells. These exosomes of tumor cells and tumor stem cells are collectively referred to herein as “tumor exosomes,” “tumor exosomal peptides,” or “tumor exosomal proteins.” Since they circulate in the reinfusion of the blood of a subject with reprogrammed tumor tissue, they may also be referred to as “circulating tumor exosomal peptides” in some embodiments herein.

[0053] In some embodiments, one of the advantages of the systems 10, 100 and methods 200, 300, 400 described herein is the multi-component nature of reprogramming, which elicits an attack by the subject's immune system against different oncological components (when reinjected into the subject's body, for example, by reinjection). This generates a broader range of multivariate antibodies that are more likely to collectively overwhelm the cancer in the subject's body (than if only one oncological component were used to induce antibody production). For example, the various oncological components may include tumor cells, tumor stem cells, and tumor degradation products, and the tumor degradation products may include tumor exosomes. This means that various cancer tissues will be attacked by various antibodies.

[0054] One way cancer cells evade the body's immune system, which would otherwise attack them, is by producing proteins (called checkpoint proteins) on their surface. These proteins signal to immune system cells that the cancer cells are normal cells of the body and not foreign invaders. In contrast, in some embodiments of systems and methods, reprogramming of tumor cells, tumor stem cells, and tumor degradation products (such as tumor DNA, tumor protoplasm, or other tumor degradation products) causes their outer surface to become a coagulated or coagulated outer surface, allowing the patient's body to attack the tumor cells, tumor stem cells, and tumor degradation products (such as tumor DNA, tumor protoplasm, or other degradation products of tumor cells or tumor stem cells). Furthermore, in some embodiments, though not bound by theory, coagulation eliminates the possibility of tumor cells and tumor stem cells producing proteins on their surface that signal the cells are normal cells and thus evade the body's immune system. Therefore, reprogrammed tumor cells, tumor stem cells, and tumor cell degradation products (such as tumor DNA, tumor protoplasm, and other degradation products of tumor cells and tumor stem cells) are the active ingredients of cancer vaccines customized for specific patients.

[0055] Furthermore, the applicant believes that once the body's immune system produces autoantibodies targeting reprogrammed tumor cells, reprogrammed tumor stem cells, and reprogrammed DNA, exosomal peptides (and other degradation products of tumor cells), these autoantibodies (or other parts of the patient's immune system) will also attack newly produced tumor cells, tumor stem cells, and nascent degradation products that are broken down, metastasized, and circulate in the patient's bloodstream (after blood purification and reinjection of reprogrammed tumor tissue).

[0056] There may be many reasons for this. One non-limiting example of such a reason, though not limited by theory, is that when antibodies attack reprogrammed tumor cells, these attacked tumor cells break down, and their internal proteins, such as DNA, are lost. The body then also attacks the mutated tumor DNA, developing further antibodies against these mutated proteins. However, these mutated proteins are similar, if not identical, to the proteins of newly metastatic tumor cells and tumor stem cells. Therefore, these further antibodies are expected to be highly effective against newly metastatic tumor cells and tumor stem cells.

[0057] Furthermore, as a result of the hemofiltration system of the system and method (in some embodiments), regularly circulating tumor cells, tumor stem cells, and tumor degradation products in the process of metastasis are removed from the patient's blood. Thus, when the reprogrammed tumor cells, tumor stem cells, and tumor degradation products are injected into the patient's body, any previous metastases occurring within the patient's body are inhibited for this further reason. Since this purification and reprogramming is performed exogenously, as in renal dialysis, some embodiments of the method described herein can be referred to as a “tumor dialysis method,” and some embodiments of the system can be referred to as a “tumor dialysis system.”

[0058] Furthermore, without being constrained or limited by theory, the applicant believes that reprogramming (e.g., coagulation) degrades the outer layers of isolated cancer tissue by removing, for example, at least one outer layer (e.g., at least one external water layer), and in some cases, the outer layers (e.g., the outer water layers 2, 3, 4, 5) surrounding the proteins of the isolated tumor tissue (cancer cells, stem cells, tumor degradation products, exosomes, etc.). Not bound by theory, the applicant also believes that unreprogrammed tumor tissue (e.g., neoplastic tumor tissue formed after reinjection of reprogrammed tumor tissue) naturally has gaps in its outer layers that expose its proteins. Therefore, autoantibodies produced by the body to attack reprogrammed tumor tissue (which may have highly exposed proteins) also immunologically detect proteins exposed by voids in the outer layer of neoplastic tumor tissue (i.e., future neoplastic tumor cells, tumor stem cells, and neodegradation products that are broken down from the tumor and metastasize and circulate in the patient's blood after blood purification and reinjection of reprogrammed tumor tissue).

[0059] The process of removing blood and purifying the tumorous components during a session by separating circulating tumor cells, circulating tumor stem cells, and their circulating components can be repeated over approximately 7 to 10 days, for example, 7, 8, 9, or 10 days, or at other intervals. If 200 cc (cubic centimeters) of blood is removed during each session, approximately 25 sessions will be required to purify all of the blood of an average adult. Shorter intervals between sessions (i.e., 6 days) are possible, as long as the patient can tolerate the blood removal (and taking into account the amount of blood removed in each session and the capacity of the hemofiltration system). Longer intervals are also possible, but the patient's ability to tolerate the tumor (and the amount of blood removed in each session) must be considered. It should be noted that the effectiveness of antibody-inducing vaccines in patients does not depend on the complete purification of the patient's blood. In fact, in some embodiments, depending on the patient's health, the patient's immune system already attacks the reprogrammed cells and cellular components, as well as the newly formed tumor cells, after one or two sessions in which the reprogrammed tumor cells, tumor stem cells, and tumor degradation products are injected into each patient and the oncogenerated components are isolated.

[0060] In some embodiments, the system and method can also be used to determine whether an asymptomatic patient has cancer. This can be used as an alternative to surgically invasive biopsy. The separated material obtained during filtration by the blood filtration system 50 is examined or tested to determine whether a tumor is present. This method can be called extracorporeal fluid biopsy (extracorporeal blood biopsy) and avoids the significant pain caused by surgically invasive biopsy. In some embodiments, the blood can be obtained minimally invasively.

[0061] Alternatively, instead of taking blood from the patient as a source for isolating tumor cells, tumor stem cells, and tumor degradation products, in some embodiments of Methods 200, 300, and 400, and in some preparations for the use of Systems 10, 100, a fluid sample may be taken from the patient's lymphatic system at the lymph node location where cancer is most likely to first spread. This is done using lymphangiogenesis (inserting a cannula into a lymphatic vessel) or sentinel lymph node biopsy (SNLB) or incision. The sentinel lymph node is the first lymph node to which cancer cells are most likely to spread (for example, in breast cancer the sentinel lymph node is the axillary lymph node, and in lung cancer the sentinel lymph node is the thoracic lymph node). Tumor cells located in the lymph nodes / lymphatic fluid may also be isolated or filtered and then reprogrammed to be reinjected intramuscularly (IM).

[0062] In one embodiment, the rotatable filter of the blood filtration system comprises multiple layers. Each of these layers has openings of different sizes for holding substances of different sizes from (i) tumor cells of different sizes, (ii) tumor stem cells, and (iii) tumor degradation products (such as tumor DNA, tumor protoplasm, or other degradation products of tumor cells or tumor stem cells).

[0063] In some embodiments, the system also includes a device for directing electromagnetic radiation to isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products (which may be one or more of tumor DNA, tumor protoplasm, tumor exosome proteins, and other degradation products of tumor cells and tumor stem cells) while these isolated components or cells are stored in a container. The container may communicate with or form part of a filtration system. The electromagnetic radiation coagulates the outer surface of at least one of (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products (e.g., DNA or other protein or cellular degradation products (tumor cells or tumor stem cells)), resulting in the formation of a coagulated outer layer on them (one or more of them). The electromagnetic radiation may have a UV wavelength. In some embodiments, another device of at least one of the devices has a terahertz frequency. In some embodiments, ozonated water and / or hydrogenated water is applied during the reprogramming stage. The system may also include a blood filtration system, as well as processing units configured to control any other hardware and software necessary to carry out the steps of Method 200 and System 10, 100 outlined herein.

[0064] Generally, for the system and method to be effective, the applicant believes that the mammalian subject must have an adequate white blood cell count and functional bone marrow. One way to test this is by testing the bone marrow of the subject's femur. This test can be performed in many ways, including non-invasively via imaging modalities. If the bone marrow in the patient's femur is 30% of the normal amount, there is a sufficient amount for the system and method to be successful. Alternatively, specialized tissue suppression therapy can be used to regenerate the subject's bone marrow. The applicant has reason to believe that a 70% success rate can be achieved in patients with at least 30% of the bone marrow. Here, success is defined as a reduction in tumor size, or at least cessation of tumor growth or metastasis, as defined by the results of PET-CT. According to the applicant, simply cessating metastasis is considered highly beneficial because, according to the applicant, it is typically not the cancer itself that directly causes the patient's death, but rather the cancer depletes the bone marrow as a result of continued metastasis, thereby impairing the body's ability to fight infection.

[0065] In some embodiments, the vaccine comprises a variety of different reprogrammed tumor-derived components from among (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products. The tumor degradation products themselves can be of various different types, including tumor DNA (and other tumor proteins), tumor protoplasm, and tumor exosomal peptides or proteins. In some embodiments, this diversity increases the likelihood that the vaccine will induce the broadest range of antibodies that can then be used against the broadest range of proteins, while simultaneously ensuring the efficacy of the antibodies because all antibodies are autologous and derived from the patient's own reprogrammed tumor tissue or components. Thus, the vaccine is tailored to the patient / subject.

[0066] The principles and operation of the personalized autologous cancer vaccine and tumor dialysis system and method for blood purification according to the present invention can be better understood by referring to the drawings and accompanying description.

[0067] Figure 1 shows one embodiment of the tumor dialysis system 10. Blood containing circulating tumor cells and circulating tumor stem cells is drawn from a vein of the subject or patient 15 and drawn in a volume of approximately 200 cc at a time or during a single treatment session in one particular non-limiting embodiment. Instead of removing approximately 200 cc in one session, different amounts may be removed, taking into account the patient's ability to tolerate blood removal and the number of sessions appropriate for the patient, taking into account the patient's health. The amount of blood that can be filtered by the hemofiltration system is also taken into consideration. Thus, generally, the amount of cc removed may vary between 40 and 300 (or, in other embodiments, any number between 40 and 200 or 50 and 300 or 40 and 300, or any other appropriate amount). In some embodiments, blood collection from the patient is achieved by a peristaltic pump 20 at the patient's venous outlet (e.g., a vein in one of the patient's arms).

[0068] As can be seen from Figure 1, in one embodiment, a first pump, for example, a first peristaltic pump 20, is configured to generate a vacuum (controlled, depending on the direction of the pump's moment) for drawing blood from the patient into the pump. Meanwhile, a second pump downstream of the hemofiltration system 50 is configured to draw blood from the pump. In one embodiment, since the blood movement generated by the peristaltic pump 20 is in the form of pulsations, a damper 30 can be placed downstream of the pump 20 to maintain a smooth flow of blood. The damper 30 may be a coil 30 arranged or formed in a cone shape downstream of the pump 20, configured to maintain a smooth flow of blood, for example, by increasing the uniformity of the blood flow rate.

[0069] In one embodiment, the coil 30 may be at least one cone-shaped or cone-arranged coil 30 to maintain a smooth flow of blood upstream of the hemofiltration system, for example, by increasing the uniformity of the blood flow velocity. The at least one cone-shaped or cone-arranged coil 30 may include at least one coil 30 configured to maintain a smooth flow of blood downstream of the hemofiltration system (for example, by increasing the uniformity of the flow rate). In some embodiments, the system 10 comprises at least one cone-shaped or cone-arranged coil 30. The coil 30 comprises a first coil 32 located upstream of the inlet of the hemofiltration system and a second coil 34 located downstream of the outlet of the hemofiltration system 50, the coils 32, 34 also prevent hemolysis, which is normal but would interfere with the purification or filtration of blood by the hemofiltration system 50. The coils slow down the blood flow velocity, so there is less turbulence or tension in the blood flow that would normally induce hemolysis, especially at the base (wider) of the coils.

[0070] The blood moves into the blood reservoir 40, and from there it passes through the inlet (not shown) of the blood filtration system 50 and moves into the blood filtration system 50.

[0071] System 10 may include a hemofiltration system 50 for filtering exogenous plasma to separate (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products (which may include one or more tumor proteins such as tumor DNA, tumor exosomal peptides, tumor protoplasm, and other tumor breakdown products). The hemofiltration system 50 may comprise a filter 52 which may have multiple layers. Each of the multiple layers may have openings of different sizes so as to hold material of different sizes between (i) tumor cells of different sizes, (ii) tumor stem cells, and (iii) tumor breakdown products. It should be noted that (i) tumor cells, (ii) tumor stem cells, and (iii) tumor breakdown products were circulating in the patient's blood when the removed blood was previously circulating in the subject / patient's body.

[0072] In some embodiments, the blood filtration system 50 may also include a filter 52. The system 50 may be configured to first filter the subject's exogenous blood to separate the exogenous plasma, before the step of filtering the exogenous plasma to separate tumor cells, tumor stem cells and / or tumor degradation products.

[0073] The blood filtration system 50 may include a filter 52 comprising one or more layers. In one version, the filter 52 is a multilayer filter 52. The filter 52 or multilayer filter 52 may be a rotatable filter 52. In the case of a multilayer filter, the multilayer filter 52 may include an outer layer 54 (Figure 3A) configured to hold tumor cells. The filter 52 or multilayer filter 52 may have an opening 55a of a first diameter. One or more intermediate layers 56 of the multilayer filter 52 may include a second outermost layer 56a configured to hold tumor stem cells and having an opening 55b of a second diameter smaller than the first diameter. In some embodiments, the multilayer filter 52 further comprises an inner layer 58 configured to hold tumor DNA and having an opening 55d of a third diameter smaller than the second diameter.

[0074] In some embodiments, the multiple layers of the rotatable filter 52 include an outermost layer 54 having an opening 55a configured to hold the largest size tumor cells, an outermost intermediate layer 56a having an opening 55b configured to hold the second largest size tumor cells, another intermediate layer 56b having an opening 55c configured to hold tumor stem cells, and an additional intermediate layer 56c having an opening 55d configured to hold tumor degradation products (such as tumor DNA or tumor protoplasm) of tumor cells or stem cells. Alternatively, there may be five layers (54, 56a, 56b, 56c, 58) or more layers with openings of different sizes. For example, there may be multiple layers with progressively decreasing diameters for holding tumor cells of different sizes, then one or more layers with smaller diameter openings (of progressively decreasing size) for stem cells, and one or more layers with even smaller diameters for tumor DNA or other degradation products (of tumor cells or tumor stem cells). Alternatively, there may be only two layers.

[0075] The blood filtration system 50 may also include a base 51 supporting a multilayer filter 52, a substantially rectangular base 51 in a non-limiting example. Any such base 51 may also support or house an actuator 53 configured to rotate the filter 52 forward and backward over a defined rotational area, for example, over a rotational area of ​​about 45 degrees (or over a rotational area of ​​30 to 60 rotational angles), as indicated by the dashed arrows in Figure 1. In a non-limiting implementation, the actuator 53 comprises one or more motors.

[0076] As the filter 52 rotates back and forth, the forces on tumor cells, stem cells, and tumor DNA cause these components to be filtered through the various layers (sometimes called the floors) of the filter 52. For example, tumor cells, stem cells, and tumor DNA can pass through (i.e., traverse) 0 to 1, 2, 3, or 4 or more layers (sometimes called the floors) of the filter 52, depending on their size and the size of the openings 55, by traversing the openings 55 or by not traversing the openings 55 in the walls of each layer or floor. In some embodiments, as seen in Figures 3A, 3B, 3C, and 3D, the aperture 55 of the filter 52 gradually decreases as it moves from the outer layer of the filter 52 toward the inner layer 58 of the filter 52.

[0077] As can be seen from Figure 1, according to one embodiment, after separation by the blood filtration system 50, tumor cells, tumor stem cells, and tumor degradation products such as tumor proteins can be subjected to electromagnetic radiation by at least one device 70 (see Figures 1 and 2) configured to direct electromagnetic radiation to them. The electromagnetic radiation may be of UV wavelength (e.g., 100-400 nm). For example, the at least one device 70 may include two or more devices, and the UV irradiation may include at least two types of UV irradiation from among (i) UVA irradiation (315-400 nm), (ii) UVB irradiation (280-315 nm), and (iii) UVC irradiation (100-280 nm). In some embodiments, the electromagnetic radiation used is of UVC wavelength, or in other embodiments, one or more of (i) UVC wavelength radiation and (ii) UVB wavelength radiation are applied. In some embodiments, the electromagnetic radiation applied is 100 nm to 300 nm (visible light is approximately 300 to 400 nm), or in some embodiments, approximately 100 to approximately 300 nm. In some embodiments, if two or three of UVA, UVB, and UVC irradiation are applied, each of UVA, UVB, and UVC irradiation may be provided separately, for example, by using separate devices 70 (i.e., two or more devices), or in other embodiments, by a single device 70. In one embodiment, only UVC irradiation is applied. In the case of tumor exosomes, in one embodiment, UVC irradiation is applied. In some embodiments, UVC irradiation of approximately 100 nm is applied, for example, approximately 100 to 110 nm or 90 to 110 nm or 100 to 120 nm or 90 to 120 nm or 100 to 130 nm or 90 to 130 nm or approximately 100 to 140 nm or approximately 100 to 150 nm.

[0078] While not bound by theory, the applicant found that UVA and UVB enhance the effects of UVC irradiation. Furthermore, UVA and UVB are weaker than UVC. Therefore, UVA and UVB coagulate the outer envelope of tumor cells and tumor stem cells, while UVC coagulates not only the outer envelope of tumor cells and tumor stem cells but also their nuclei. In fact, UVC often kills tumor cells and tumor stem cells. These dead cells are effective in inducing autoantibody production by the subject's immune system (once re-introduced into the subject's body). Generally, different tumor cells or tumor stem cells require different frequencies of electromagnetic radiation to coagulate their outer envelopes, so it is useful to use UVA, UVB, and UVC irradiation to maximize the effect.

[0079] Therefore, in one implementation, UVA irradiation, UVB irradiation, and UVC irradiation 720 are each directed to one or more (in other embodiments two or more, or in other embodiments three or more) isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products (of tumor cells or stem cells, which may include tumor DNA or other tumor proteins, tumor exosomes (such as tumor exosomal peptides), tumor protoplasm, or other tumor degradation products) by at least one device 70, which may be at least one radiation device 70. This may be performed by different devices 70 (i.e., different radiation devices 70) for each type of irradiation, and this may be performed sequentially (i.e., not simultaneously). In one version, UVA irradiation is first applied by one device 70 for 5 to 9 seconds, then UVB irradiation is applied by a second device 70 for 5 to 9 seconds, and then UVC irradiation is applied by a third device for 5 to 9 seconds. In other implementations, either UVA or UVB irradiation is applied, and UVC irradiation is also applied (in one implementation of this example, UVA is applied followed by UVC, or UVB is applied followed by UVC). In some embodiments, only one type of radiation is applied.

[0080] In one embodiment, each type of electromagnetic radiation 720 to which UV irradiation 720 is applied is continuously irradiated for a period of about 5 to about 9 seconds (or some time between about 5 seconds and less than about 9 seconds) to one or more (in other embodiments, two or more, or in other embodiments, three or more) of isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products of tumor cells or stem cells.

[0081] In some embodiments, at least one device 70 further includes a device 72 for directing electromagnetic radiation 720 to one or more (at least two in other embodiments, or all three in other embodiments) of isolated tumor cells 91, isolated tumor stem cells 92, and isolated tumor degradation products (e.g., including tumor DNA 93), or other degradation products for generating a coagulated outer layer 91a, 92a, 93a, wherein the electromagnetic radiation 720 has a terahertz frequency up to about 0.1 terahertz (at least about 2,997,924.58 nm, or at least about 3 million nm in other embodiments).

[0082] In any embodiment described herein, electromagnetic radiation 720 (e.g., UVC or any other electromagnetic radiation 720) guided by at least one device 70 can degrade the outer layer of isolated tumor tissue (tumor cells, tumor stem cells and / or tumor degradation products) to expose proteins beneath such outer layer.

[0083] One embodiment of System 10 is a system for preparing a cancer vaccine for a mammalian subject having circulating tumor tissue. System 10 may include a hemofiltration system 50 for filtering exogenous plasma to separate oncogeneic components (e.g., from the plasma). The oncogeneic components comprise at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor disintegration products, and the oncogeneic components are not configured to be recognized as antigens by the subject's immune system. The oncogeneic components mainly consist of at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor disintegration products, and the plasma residue may contain less than about 5% by volume or less than about 1% by volume in some embodiments, or less than about 0.5% by volume in some embodiments, or less than 0.1% by volume in some embodiments.

[0084] System 10 may also include at least one device 70 for directing electromagnetic radiation 720 to the isolated tumor component so as to convert the outer surface of at least one of (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products into a coagulated outer layer, thereby converting the tumor component into something that the subject's immune system will recognize as an antigen when the tumor component is reinserted into the subject's body (e.g., when it is reinserted or reinjected into the subject's bloodstream after its outer surface has been coagulated, degraded, or altered). The electromagnetic radiation may have a UV wavelength. One example of converting a tumor component into something that the immune system will recognize as an antigen is by degrading the outer layer of the isolated tumor tissue, for example, by degrading the water in the outer layer of the isolated tumor tissue, which can cause coagulation of the outer layer of the isolated tumor tissue.

[0085] System 10 may also include a processing unit 80 configured to control the blood filtration system 50. The processing unit 80 may include one or more processors 82 that execute program instructions 84, such as software 84 stored in memory 86. System 10 may also include any other hardware of the software required to implement the system.

[0086] In some embodiments, the hemofiltration system 50 is configured to separate the yield of tumorigenic components from exogenous plasma (which can then be subjected to reprogramming). The yield of tumorigenic components may still contain only plasma residue, e.g., negligible plasma residue. In some embodiments, the negligible plasma residue in the separated tumorigenic components is less than about 5 vol%; in some embodiments, less than about 1 vol%; in some embodiments, less than about 0.5 vol%; in some embodiments, less than about 0.1 vol%; and in some embodiments, a different percentage (or less than another percentage), such as 1% to 5%, 0.5% to 1%, or 0.1% to 0.5%. Thus, when reprogramming the separated tumorigenic components using electromagnetic radiation 720 to break down the outer layer of tumor tissue and produce a coagulated outer layer, for example, in some embodiments, the advantage is achieved that cancerous proteins rather than healthy proteins are irradiated. As a result, when the reprogrammed tumor tissue is reinserted or reinjected into the subject's body, the antibodies induced by the subject's immune system are formed against the tumor tissue and not against healthy proteins. This minimizes autoimmune disease caused by antibodies.

[0087] In addition, in some embodiments, system 10 has the advantage of separating multiple types of oncological components (rather than a single type) so that when reprogramming and reinsertion into the body occurs, system 10 is configured to induce an attack by the subject's immune system against multiple diverse tumor tissues from which it has been separated. Thus, the immune system's attack by autoantibodies against the reprogrammed tumor tissue is more diverse and complete than in prior art systems. For example, the oncological components may include at least two, or in other cases all three, of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products. Furthermore, in some embodiments, the separated oncological components may also include tumor degradation products that may include tumor exosomes (in this case, the hemofiltration system may also include a centrifuge) and / or DNA. In one embodiment of system 10, as part of the reprogramming, system 10 further includes a device 71 (Figure 5) configured to provide ozonated water to be applied to the isolated tumor cells, isolated tumor stem cells, and isolated tumor DNA or other tumor degradation products (outer surface) after the application of UV irradiation, preferably UVC (and / or UVA and / or UVB). Ozone-treated water can have a concentration of approximately 5 mcg to 15 mcg per 1 ml of solution. When used, ozone-treated water helps to further ensure that coagulation occurs.

[0088] In one embodiment, system 10 includes a device 72 (Figure 5) configured to apply hydrogenated water to the outer surface of isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products, either before, after, or independently of the application of ozonated water. In some embodiments, the hydrogenated water has a pH of 8–10 and an oxidation-reduction potential of -400mV to -800mV. As a result, the hydrogenated water creates an alkaline environment, killing circulating tumor cells and tumor stem cells and tumor degradation products, even though they retain their basic cellular morphology. Dead tumor cells (as opposed to living tumor cells) are more likely to be recognized as antigens by the organism.

[0089] The same applies to frozen tumor cells and frozen tumor degradation products, which (in contrast to unfrozen tumor cells and tumor degradation products) are more likely to be recognized as antigens by the patient's immune system. In some embodiments, one or more of the reprogrammed tumor cells, reprogrammed tumor stem cells, and reprogrammed tumor degradation products (i.e., DNA) are frozen (before being injected into the subject). The length of the freezing time is, in some embodiments, the amount of time sufficient to cause crystallization of one or more of the tumor cells, tumor stem cells, and tumor degradation products. For example, the freezing time may be about 5 to 13 minutes, or in some embodiments about 8 to 10 minutes (or another length of time configured to cause crystallization). In some embodiments, freezing occurs by setting the temperature of the container body in which the tumor cells and degradation products are placed to a temperature somewhere between about -5°C and about -10°C. Freezing is performed before the reprogrammed cells / components are injected into the patient. This freezing causes crystallization of the tumor cells, tumor stem cells, and tumor degradation products (such as peptides), increasing the likelihood that the subject's immune system will recognize these cells or components as antigens.

[0090] As shown in Figure 5, reprogramming of at least one of tumor cells, tumor stem cells, and tumor degradation products (such as DNA or other degradation products) may occur while the tumor cells or tumor stem cells or tumor degradation products are in container 60, but this is not a requirement.

[0091] Reprogrammed tumor cells, reprogrammed tumor stem cells, and at least one of the reprogrammed tumor degradation products can, according to some embodiments, then be injected into the muscles of the patient 15, for example, in the buttocks (or delivered into the subject / patient's body in some other way) (during or after the reprogramming process). In addition, the purified or cleaned blood (after passing through a further peristaltic pump 20 and a further conically arranged coil 30, according to some embodiments) is recirculated in some embodiments by a further tube 29 into the subject / subject's veins (typically in the veins of the subject's other arm, not the vein of the arm from which the blood was drawn).

[0092] Therefore, electromagnetic radiation 720 (and in some versions, one or more of ozonated water, hydrogenated water, and freezing (e.g., about 5 or 6 or 7 or 8 to about 10 or about 11 or about 12 or about 13 minutes (e.g., 8 to 10 minutes)) causes the outer layer of each isolated component applied (tumor cells 91, tumor stem cells 92, and tumor cell degradation products 93 such as tumor DNA 93) to coagulate or form coagulated outer layers 91a, 92a, 93a, and thus undergoes substantially "reprogramming" which results in these component antigens inducing autoantibody production by the patient's immune system when injected into the subject / patient. In some embodiments, the injection of the vaccine described herein into the subject occurs immediately after reprogramming (within a few hours), so there is no need to utilize preservatives as part of the vaccine.

[0093] Furthermore, the blood that is recirculated to the patient is purified blood from which circulating (metastatic) tumor cells and circulating tumor stem cells, as well as their respective degradation products (i.e., DNA and other tumor degradation products), have been removed by the hemofiltration system 50 (for example, largely removed in some embodiments).

[0094] System 10 may also include a processing unit 80 configured to control the blood filtration system 50. The processing unit 80 may include one or more processors 82 that execute program instructions 84, such as software 84 stored in memory 86. Systems 10, 100 may also include any other hardware of software required to implement the system (or any method 200 described herein). The processor 82 can control the frequency at which the actuator 53 or another component rotates the filter 52 back and forth over a defined rotational area. If the yield of tumor cells, tumor stem cells, or tumor degradation products (after examination) is not high enough to meet a predetermined criterion, the processor 82 may change the frequency and magnitude of the area (rotation angle) over which rotation occurs. In some embodiments, artificial intelligence, such as machine learning, is used by the processor 82 to perform these functions, including controlling the frequency of rotation of the filter 52, controlling the magnitude of the area (i.e., rotation angle) over which rotation occurs, and determining whether the yield of the filter 52 meets a desired predetermined threshold amount of tumor cells, tumor stem cells, and / or tumor degradation products.

[0095] In another embodiment, as shown in Figure 4, the system 100 does not include the at least one device 70 described above. The system 100 may include at least one coil 30 (coils 32, 34, etc.). For example, the system 100 may comprise a system 100 for purifying the blood of a mammalian subject having a cancerous tumor, which includes a hemofiltration system 50 for filtering exogenous blood. The filtration system 50 can filter plasma from the remainder of the exogenous blood. In some embodiments, the filtration system 50 of the system 100 is configured to start with exogenous plasma as input. In this case, the filtration system 50 is configured to filter and isolate at least one (or at least two in some other embodiments, or all three in some other embodiments) of tumor degradation products such as (previously circulating) tumor cells, (previously circulating) tumor stem cells, and (previously circulating) DNA.

[0096] The blood filtration system 50 may include a rotatable filter 52 having multiple layers.

[0097] As can be seen from Figure 4, the system 100 may include at least one cone-shaped or cone-shaped coil 30. The coil 30 comprises a first coil located upstream of the inlet of the blood filtration system and a second coil 30 located downstream of the outlet of the blood filtration system 50. The system 100 may also include a processing unit 80 (including machine learning and artificial intelligence in any version described with respect to the system 10) configured to control the blood filtration system 50.

[0098] Any version of the elements of system 10 (other than the device 70) can be used in each element of system 100. For example, any version of the blood filtration system 50 (or its layer) or coil 30 described in relation to system 10 can be used in the blood filtration system 50 or coil 30 of system 100. Similarly, a pump 20 may be present in system 100, just as it may be present in system 10.

[0099] In one embodiment, system 10 or system 100 may also include a centrifuge 57 (Figure 3E) useful for separating tumor exosomes 94. This is important because even exosomes from healthy cells are programmed to eventually leave the cell. When tumor exosomes 94 leave tumor cells or tumor stem cells, this constitutes (or causes) metastasis. Furthermore, since exosomes leave healthy cells earlier than cellular apoptosis, the exit of tumor exosomes 94 from tumor cells or tumor stem cells can occur even before primary proliferation (tumor cells or tumor stem cells) metastasizes, without being constrained or limited by theory.

[0100] The applicant believes that the detection of tumor exosomes 94 or tumor exosomal peptides 94 in the blood offers significant advantages to filtering and removing tumor exosomes 94, reprogramming them (e.g., by exposing the outer surface of tumor exosomes 94 to electromagnetic radiation, for example, by coagulating the outer surface), and reinjecting the reprogrammed tumor exosomes into the patient's body. Since the exit of tumor exosomes 94 occurs before clinical symptoms appear, in some embodiments, a vaccine based on injecting reprogrammed tumor exosomes into a patient can stimulate autoantibodies against the tumor as early as possible in metastasis. In some embodiments, this is before the onset of clinical symptoms. Furthermore, since tumor exosomes (and exosomes in general) contain cellular RNA and DNA from which they emanate, in some embodiments, a vaccine developed from reprogrammed tumor exosomes is effective in stimulating autoantibodies to attack the entire tumor.

[0101] Furthermore, the mere purification of the blood from tumor exosomes 94 (without reinjecting the coagulated tumor exosomes after their reprogramming) is also important. This is because the applicant believes that exosomes (including tumor exosomes), due to their small size (approximately 50-80 nanometers), can penetrate the blood and brain barriers, causing obviously dangerous disruption within the brain (e.g., metastasis).

[0102] Figure 3E shows a centrifuge 57 of a hemofiltration system 50 in which tumor exosome fragments are separated from plasma 99 and reprogrammed by at least one device 70 using electromagnetic radiation. Thus, in some embodiments of system 10, system 10 includes a centrifuge 57, as shown in Figure 3E. In particular, the hemofiltration system 50 may include a centrifuge 57 configured to separate tumor exosomes 94 from plasma 99, for example, by separating tumor exosomes 94 from plasma 99 in a stepwise centrifugation process. In some embodiments, the centrifuge 57 is generally used to do this after the plasma of tumor cells 91, tumor stem cells 92, and tumor degradation products 93 has been previously purified. Since tumor exosomes 94 are smaller than other tumor degradation products, tumor exosomes are not separated in the step prior to purifying the plasma.

[0103] The centrifugation process by stepping with a centrifuge 57 may include using the centrifuge 57 at a first speed (e.g., about 1,000 rpm (e.g., 750–1,250 rpm)), then using the centrifuge 57 (or theoretically a different centrifuge) at a second speed (e.g., 5,000 rpm or 4,000–6,000 rpm), and then using the centrifuge 57 (or a different centrifuge) at a third speed (e.g., 7,000 rpm or 6,000–8,000 rpm) to finally obtain tumor exosome fragments 94 (Figure 3E). This is because tumor exosomes may be the lightest of the separable components of the centrifuged plasma 99. The tumor exosomes 94 are then available to be reprogrammed by applying electromagnetic radiation to the outer layer of the tumor exosomes 94 using at least one apparatus 70 (e.g., using UVC).

[0104] In some cases, "G" is used instead of "rpm" as the unit of centrifugal separation. In that case, the relative centrifugal force is set to G in the first step, G+x in the second step, and G+y in the third step, where y is greater than x.

[0105] In some embodiments, the duration of centrifugation using the centrifuge 57 at a first speed is approximately 1 minute, the duration at a second speed is approximately 1 minute, and the duration at a third speed is approximately 3 to 5 minutes. These durations are merely examples and are not limiting.

[0106] Furthermore, as shown in Figure 3E, at least one apparatus 70 may be configured, in some embodiments, to direct electromagnetic radiation 720 (e.g., UVC irradiation) to the isolated tumor exosomes 94 to produce a coagulated outer layer 94a of the tumor exosomes 94. Although tumor exosomes are a type of tumor degradation product 93, tumor exosomes isolated using the centrifuge 57 are assigned a separate reference number "94" because the isolation of such tumor exosomes 94 occurs through a separate process using this centrifuge 57.

[0107] As shown in Figure 6, another embodiment is a method 200 for purifying exogenous blood and preparing a vaccine against cancer in a mammalian subject using components of the exogenous blood. Method 200 may include step 210 of filtering the exogenous plasma to separate oncogeneic components, which consist mainly of one or more tumor cells, tumor stem cells, and tumor lysis products. Here, such tumor lysis products may include one or more tumor DNA, tumor proteins or tumor peptides, or tumor exosomes or tumor exosomal peptides. Here, the oncogeneic components are not configured to be recognized as antigens by the subject's immune system.

[0108] The isolated neoplastic component may consist mainly of at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products. The isolated neoplastic component may consist only of the remainder of the plasma, containing less than about 5% by volume, or less than about 1% by volume, or less than about 0.5% by volume, or less than 0.1% by volume, in some embodiments.

[0109] In some versions, mature circulating tumor cells are first isolated, and then tumor stem cells are isolated. In some versions of Method 200, Method 200 includes only the step of filtering the patient's plasma to isolate one or more of the tumor cells, tumor stem cells, and tumor degradation products such as DNA, and filtering the exogenous blood to obtain plasma, which is not part of Method 200.

[0110] Method 200 may also include step 220 of directing electromagnetic radiation to one or more of (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products (such as DNA or tumor exosomal peptides or proteins) so that they each acquire a coagulated outer surface or layer 91a, 92a, 93a, thereby converting the tumor component into something that the subject's immune system will recognize as an antigen when the tumor component is reinserted into the subject's body.

[0111] In some embodiments, directional electromagnetic radiation 720 causes coagulation of the outer layer of isolated tumor tissue (i.e., (i) isolated tumor cells, (ii) isolated tumor stem cells, and / or (iii) isolated tumor degradation products which may contain DNA and / or tumor exosomes or tumor exosomal peptides). Degradation may occur by removing at least one outer layer (e.g., at least one outer aqueous layer) and possibly two, three, four, or five outer layers (e.g., two, three, four, or five outer aqueous layers) surrounding the proteins of the isolated tumor tissue (tumor cells, tumor stem cells, tumor degradation products, DNA, exosomes, etc.). The depiction of tumor degradation products 93 in Figure 2 is just one non-limiting example.

[0112] In some embodiments, the electromagnetic radiation 720 directed to the tumor tissue has wavelengths in the UV range. In some embodiments, the UV irradiation is UVC irradiation. In some embodiments, the UV irradiation is UVC irradiation and one of UVA or UVB irradiation. In one non-limiting version, the UV irradiation includes at least two of UVA irradiation, UVB irradiation, and UVC irradiation, and UVA irradiation, UVB irradiation, and UVC irradiation are provided separately. In some embodiments, the UV irradiation includes UVA irradiation, UVB irradiation, and UVC irradiation, each applied separately. Similar to system 10, in step 220 of method 200, the electromagnetic radiation 720 may be irradiated for about 5 seconds to about 9 seconds (each type of radiation (UVA, UVB, UVC)), or any in between. Applying electromagnetic radiation (specifically UVC irradiation) for longer than 9 seconds carries the risk of causing undesirable mutations.

[0113] In one embodiment, step 220 includes directing electromagnetic radiation using an apparatus 70 (any version of the apparatus 70 described with respect to system 10) configured to irradiate tumor cells, tumor stem cells and DNA (or other degradation products of tumor cells) with electromagnetic radiation up to 0.1 terahertz.

[0114] Method 200 may also include the step of using a processing unit 80 to control plasma filtration, for example, by controlling a hemofiltration system 50 that performs plasma filtration.

[0115] In one embodiment of Method 200, step 220 further comprises applying ozonated water to isolated tumor cells, isolated tumor stem cells, and isolated DNA or other degradation products of tumor cells. The ozonated water may have a concentration of about 5 to about 15 mcg per ml of solution. Method 220 may also comprise applying hydrogenated water to at least one of the isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products to create an alkaline environment. For example, the hydrogenated water may have a pH of about 8 to about 10 and an oxidation-reduction potential of about -400 to -800 mV. Step 220 may also, in some embodiments, comprise freezing and crystallizing one or more of the reprogrammed tumor cells, reprogrammed tumor stem cells, and reprogrammed tumor degradation products for, for example, about 5 to 13 minutes, or in some embodiments about 8 to about 10 minutes, before injecting them into a subject, thereby increasing the likelihood that the subject's body will recognize them as antigens.

[0116] Method 200 may include a further optional step of injecting the patient with irradiated DNA, pre-circulating tumor cells, and tumor stem cells to induce the patient's immune system to produce autoantibodies against the coagulated outer surface.

[0117] In step 210 of Method 200 (and generally in any of the other Methods 300, 400), any version of the filtration system 50 and filter 52 described with respect to System 10 or System 100 may be used.

[0118] As one non-limiting example, method step 220 may include filtering the patient's plasma using a hemofiltration system 50 that includes a filter, such as a multilayer filter which may be a rotatable filter. Each layer of the multilayer filter may be configured for tumor cells or tumor cell degradation products of different sizes. Similarly, method step 210 may include using a rotatable filter. In some embodiments, the rotatable filter has an outer layer configured to hold tumor cells and having an opening of a first diameter, and a second layer configured to hold tumor stem cells and having an opening of a second diameter smaller than the first diameter, the rotatable filter further comprises an inner layer configured to hold tumor DNA and having an opening of a third diameter smaller than the second diameter. Method step 210 may include utilizing a rotatable filter that includes an outermost layer having an opening configured to hold the largest size tumor cells, an inner layer (a layer inside the outermost layer) having an opening configured to hold the second largest size tumor cells, an intermediate layer having an opening configured to hold tumor stem cells, and an additional layer having an opening configured to hold tumor DNA.

[0119] Method step 210 may include subjecting the filtered material (e.g., tumor cells or tumor stem cells or tumor degradation products) to oncological evaluation to determine whether they are tumor cells or not. Such evaluation procedure may include staining cells (or samples thereof) that were too large to pass through a particular layer of the filter, and then observing these cells under a microscope to determine whether they are actually cancerous. The aforementioned oversized cells are, for example, cells that were too large to pass through the opening 55a and were therefore retained by the outer layer 54. This may be quantitatively compared to the amount of one or more tumor cells, tumor stem cells, and tumor degradation products that were present before filtration in method step 210. The previous amount may be evaluated in a further substep of method step 210.

[0120] Method 200 may include placing at least one cone-shaped or cone-shaped coil upstream of the inlet of the hemofiltration system, and optionally placing at least one cone-shaped or cone-shaped coil downstream of the outlet of the hemofiltration system. Each of these is for the purpose of improving the uniformity of blood flow velocity and preventing hemolysis, which impedes blood purification.

[0121] As shown by the flowchart in Figure 7, one embodiment of Method 300 is a method for purifying the blood of a mammalian subject having a cancerous tumor, the blood having circulating tumor cells, tumor stem cells, and / or tumor degradation products. This is similar to Method 200, except that it omits the steps of reprogramming one or more of the isolated tumor cells, isolating tumor stem cells, and isolating tumor degradation products. Method 200 may include a step 310 of filtering the exogenous blood to obtain plasma. This can be done using a centrifuge. Method 300 may also include a step 320 of filtering the obtained plasma to isolate at least one of the tumor cells, tumor stem cells, and tumor degradation products. This step 320 can be performed using any version of System 10, 100 or filtration system 50 of Method 200, and any version of Method Step 210 of Method 200, including any substep or version thereof.

[0122] In one version of Method 200 or Method 300, the Method further comprises separating tumor exosomes 94 from plasma by a stepwise centrifugation process using a centrifuge 57 after, for example, the purification of plasma 99. The stepwise centrifugation process may include using the centrifuge 57 at a first speed, then at a second speed, then at a third speed, to finally obtain tumor exosomes. The first speed may be 750–1250 rpm (e.g., applied for about 1 minute), the second speed may be 4000–6000 rpm, and the third speed may be 6000–8000 rpm (e.g., applied for about 3–5 minutes). These speeds and time intervals are merely illustrative and non-limiting.

[0123] Method 300 may also include the step of using a processing unit 80 to control the filtration of plasma, for example, by controlling a hemofiltration system 50 that performs the step of filtering plasma to separate at least one of tumor cells, tumor stem cells, and tumor degradation products.

[0124] One implementation of Method 300 includes purifying plasma by removing tumor cells, tumor stem cells, and tumor degradation products (all three), and returning the purified plasma to the patient's blood from which the plasma was separated (e.g., the original 200 cc). Further versions also include recirculating the reconstituted purified blood to the patient (e.g., through the patient's vein). This process of purifying or cleaning the blood from oncological components (cells, degradation products) may be repeated many times (e.g., 25 times for an average adult if 200 cc of blood is removed in each session) until all of the patient's blood is purified from circulating tumor cells, tumor stem cells, and tumor degradation products, in some embodiments.

[0125] As shown in Figure 8, Method 400 is a method for purifying exogenous blood and preparing a vaccine against cancer in a mammalian subject using components of the exogenous blood. Method 400 may include step 410 of filtering the subject's exogenous human blood to separate the plasma. The exogenous blood may be about 200 cc of blood (or another suitable amount as described herein with respect to any method or system) or may be blood removed from the patient during that session. Filtration of the blood to obtain plasma can be performed by centrifugation, taking advantage of the fact that plasma is more liquid than the rest of the blood.

[0126] Method 400 may also include step 420 of filtering the plasma to separate the oncogenetic components, which are mainly one or more of tumor cells, tumor stem cells, and tumor degradation products. The separated oncogenetic components may mainly consist of at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products. The separated oncogenetic components may, in some embodiments, consist only of the remainder of the plasma containing less than about 5 vol% or less than about 1 vol% or, in some embodiments, less than about 0.5 vol% or, in some embodiments, less than 0.1 vol% of the oncogenetic components.

[0127] Any filtration system 50 described herein with respect to systems 10, 100 or methods 200, 300 (including any version of step 210 of method 200 or step 320 of method 300) may be suitable for step 420. In some versions, mature circulating tumor cells are first isolated, and then tumor stem cells are isolated.

[0128] Method 400 may also include step 430 of directing electromagnetic radiation to one or more of (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products (e.g., DNA) so that they acquire a coagulated outer surface or layer 91a, 92a, 93a, respectively. This is a reprogramming step to induce the production of autoantibodies, as described, when the vaccine is injected. In some embodiments, the electromagnetic radiation has wavelengths in the UV range. In some embodiments, the UV irradiation is UVC irradiation. In some embodiments, the UV irradiation is UVC irradiation and one of UVA or UVB irradiation. In one non-limiting version, the UV irradiation includes at least two of UVA irradiation, UVB irradiation, and UVC irradiation, and UVA irradiation, UVB irradiation, and UVC irradiation are provided separately. In some embodiments, the UV irradiation includes UVA irradiation, UVB irradiation, and UVC irradiation. In some embodiments, each is applied separately for about 5 to 9 seconds. Any version of the reprogramming step described herein with respect to System 10 or Method 200 may be used in Method 400. For example, step 430 may include the application of hydrous water, ozone, and / or the freezing of one or more tumor cells, tumor stem cells, and tumor degradation products. For example, Method 100 may include any version of the type or combination of several types of UV irradiation and the length of time the radiation is applied, as described with respect to System 10 or Method 200.

[0129] Method 400 may also include the step of using a processing unit 80 to control the filtration of plasma, for example, by controlling a hemofiltration system 50 that performs the step of filtering the plasma to separate at least one of tumor cells, tumor stem cells, and tumor degradation products.

[0130] Some implementations of Method 200 or Method 400 include the step of applying electromagnetic radiation to form a coagulated outer surface of at least one of tumor cells, tumor stem cells, and tumor degradation products, The method comprises the steps of applying hydrogenated water having a pH of approximately 8 to approximately 10 and an oxidation-reduction potential of approximately -400 to -800 mV to at least one of isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products, and freezing at least one of the isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products for at least 5 minutes.

[0131] In any version of Methods 200, 300, and 400, some embodiments may also include one or both of the following additional steps “a)” and “b).

[0132] a) Before reprogramming one or more of the isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products, organize a large population of tumor cells, tumor stem cells, or tumor degradation products by cloning one or more of the isolated tumor cells, isolated tumor stem cells, and isolated tumor degradation products and placing them in animal plasma or the subject's own plasma, thereby organizing a “medium / suspension” that acts as nutrients for these isolated tumor cells, tumor stem cells, and tumor degradation products and helps them to grow and replicate. This growth and replication will occur naturally (but other known techniques for growth and replication may be added if desired). Then, the reprogramming step(s) is performed on the cloned population.

[0133] b) After the reprogramming step of any of methods 200, 300, or 400, the reprogrammed material (i.e., one or more of tumor cells, tumor stem cells, and tumor degradation products) is added to antigen-presenting cells (APCs) including macrophages, B cells, and dendritic cells in solution. This can be achieved by collecting peripheral blood (from the same subject from which the exogenous blood was collected), for example by venotomy, running a cycle in a centrifuge to separate the whole blood components, then collecting only the white blood cells (WBCs), and placing these (or only the APCs in the WBCs) in solution (suspension). This results in a faster-acting vaccine because the inventors allow the subject's exhausted immune system to skip at least one step in the process of converting the immune system from a tolerogenic (receptive) state to an immunogenic (tumor-degrading) state. The immune system (once the vaccine is injected) and the APCs no longer need time to spontaneously find the reprogrammed tumor cells, stem cells, and tumor degradation products. B cells and T cells can process tumor cells without waiting for antigen-presenting cells to find them, and can act immediately without coupling their peptides to the surface of immune system cells (T cells and B cells).

[0134] In any of the Systems 10, 100 or Methods 200, 300, 400 herein, the isolation of a neoplastic component comprising (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products, or the isolation of a neoplastic component comprising (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products, does not necessarily mean that these elements of the neoplastic component are separated from each other. In some embodiments, they are separated from each other, and in some embodiments, they are not separated from each other (whole or partially).

[0135] Similarly, in any system 10, 100 or method 200, 300, 400 herein, in some implementations of reprogramming isolated oncological components (i.e., at least one or at least two or all of (i) isolated tumor cells, (ii) isolated tumor stem cells, and (iii) isolated tumor degradation products), these elements of the oncological components are not necessarily separated from one another. In some implementations of reprogramming isolated oncological components, they are not separated from one another in whole or in part, and in some implementations they are separated from one another.

[0136] In any system or method of the present application, the dose of the reinjected and reprogrammed neoplastic tissue (i.e., tumor cells, tumor stem cells, and / or tumor degradation products including tumor exosomal peptides, exosomal DNA, or RNA) does not need to be large enough to induce the immune system to produce antibodies. In one non-limiting example, the dose of each type of neoplastic component or tissue (i.e., tumor cells, tumor stem cells, tumor degradation products including subtypes of such tumor degradation products such as tumor exosomal peptides, exosomal DNA, or exosomal RNA) comprises 8 to 25 micrograms or 10 to 15 micrograms.

[0137] In any embodiment of the method or system of the present application, when the method or system is used, reinjection of the tumor component is contemplated for future action, or in any embodiment in which reinjection is included in the method / system, reinjection may be performed immediately after reprogramming of the tumor component. Reinjection may be performed intramuscularly, subcutaneously and / or intradermally (or via any other method referred to herein).

[0138] Alternatively, in any embodiment, instead of reinjecting the tumor component, in some versions, the reprogrammed tumor component is stored or preserved, for example, in a refrigerator, where the cells of the tumor component can be proliferated, for example, provisionally in case mutations are present in the subject, for use in future vaccines.

[0139] As used in this application, the term “about” may be used to specify a value of a quantity or parameter that lies within a continuous range of values ​​in the vicinity (and including) a given (stated) value. In particular, “about” means that the value of a parameter is between 95% and 105% of a given value.

[0140] Although the present invention has been described in relation to a limited number of embodiments, it will be understood that many variations, modifications, and other applications of the present invention are possible. Accordingly, the claimed invention, as described in the following claims, is not limited to the embodiments described herein.

Claims

1. A system for preparing an autologous cancer vaccine for a mammalian subject, wherein the system uses components of the subject's own exogenous blood without using surgically invasive biopsy of the subject. The aforementioned system, A hemofiltration system for filtering autologous exogenous plasma to remove neoplastic components from autologous exogenous plasma, wherein the neoplastic components include at least one of (i) tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products, and the neoplastic components are not recognized as antigens by the subject's immune system. A coil having a base at its widest point and located upstream of a hemofiltration system, arranged or formed in a conical shape, wherein the base is configured to receive peristaltically flowing exogenous plasma, and the coil is configured to increase the uniformity of the flow rate of the exogenous plasma output to the hemofiltration system, thereby inhibiting hemolysis of the exogenous plasma, (i) converting the outer surface of at least one of tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products into a coagulated outer layer, thereby guiding electromagnetic radiation to the removed tumor component so that the removed tumor component can be recognized as an antigen by the subject's immune system having a UV wavelength, A processing unit configured to control the blood filtration system, A system that includes this.

2. The hemofiltration system is configured to filter the autologous exogenous plasma output from the cone-shaped or cone-shaped coil to remove a plurality of types of tumor components, the plurality of types comprising at least two tumor cells, tumor stem cells and tumor degradation products, none of the plurality of types of tumor components are recognized as antigens by the subject's immune system, and the system according to claim 1, wherein at least one device is configured to convert each of the at least two of the plurality of types of removed tumor components into antigens by directing electromagnetic radiation to each of the at least two of the plurality of types of removed tumor components, so that each of the at least two of the removed tumor cells, tumor stem cells and tumor degradation products has a coagulated outer surface that is recognizable as an antigen by the immune system.

3. The system according to claim 1, wherein the tumor component comprises a tumor degradation product, and the tumor degradation product comprises a tumor exosomal peptide.

4. The system according to claim 1, wherein the at least one device further includes a device for directing electromagnetic radiation to at least one of removed tumor cells, removed tumor stem cells, and removed tumor degradation products to produce a coagulated outer layer, wherein the electromagnetic radiation has a terahertz frequency up to 0.1 terahertz.

5. The cone-shaped arrangement or cone-shaped coil is located upstream of the blood filtration system. A peristaltic pump is further provided upstream of the cone-shaped or cone-shaped coils. The system according to claim 1, wherein the cone-shaped arrangement or cone-shaped coil is configured to receive the exogenous plasma flowing from the peristaltic pump.

6. (i) a peristaltic pump downstream of the hemofiltration system, and (ii) an additional coil located downstream of the hemofiltration system, having its base at its widest part, arranged or formed in a cone shape, The coil according to claim 1, wherein the additional coil is configured to receive the exogenous plasma flowing from the pump and to inhibit hemolysis of the exogenous plasma by increasing the uniformity of the flow velocity of the exogenous plasma output from the peristaltic pump.

7. The system according to claim 1, wherein the filter has a plurality of layers, each of the plurality of layers having openings of different sizes to hold materials of different sizes from among (i) one or more sizes of tumor cells, (ii) tumor stem cells, and (iii) tumor degradation products.

8. The aforementioned filter, The outer layer is configured to hold the tumor cells and has an opening of a first diameter, A second layer configured to hold the tumor stem cells and having an opening with a second diameter smaller than the first diameter, The system according to claim 7, having the following features.

9. The aforementioned filter, The system according to claim 8, further comprising an inner layer configured to hold the tumor degradation product and having an opening of a third diameter smaller than the second diameter.

10. Multiple layers of the aforementioned filter, The outermost layer has an opening configured to hold the largest tumor cells, An inner layer having an opening configured to hold the second largest size tumor cell, An intermediate layer having an opening configured to hold tumor stem cells, An additional layer having openings configured to retain tumor degradation products, The system according to claim 7, including the system described in claim 7.

11. The blood filtration system according to claim 1, wherein the blood filtration system includes an actuator configured to rotate the filter back and forth over a defined rotational area.

12. The system according to claim 1, wherein the hemofiltration system is configured to filter the exogenous blood of the subject in order to isolate the exogenous plasma.

13. The system according to claim 1, further comprising the removed tumor component, wherein the removed tumor component comprises two or more of the following: (i) the removed tumor cells, (ii) the removed tumor stem cells, and (iii) the removed tumor degradation products.

14. The system according to claim 1, further comprising the removed tumor component, wherein the removed tumor component comprises (ii) the removed tumor cells, and (iii) the removed tumor degradation products.

15. The aforementioned at least one device, A device configured to guide UVA irradiation, A device configured to guide UVB irradiation, A device configured to direct UVC irradiation to one or more of the removed tumor cells, (ii) removed tumor stem cells, and (iii) removed tumor degradation products, The system according to claim 1, including the following:

16. The system according to claim 1, wherein the removed tumorous component consists only of the remainder of the plasma, which is less than about 5% by volume of the separated tumorous component.

17. The system according to claim 1, wherein the removed tumorous component consists only of the remainder of the plasma, which is less than about 1 volume percent of the separated tumorous component.

18. The system according to claim 1, wherein the removed tumorous component comprises only the remainder of the plasma, which is less than approximately 0.5% by volume of the separated tumorous component.

19. The system according to claim 1, wherein the removed tumorous component consists only of the remainder of the plasma, which is less than about 0.1 volume percent of the separated tumorous component.

20. The system according to claim 1, wherein the removed tumorous component comprises at least two of (i) the removed tumor cells, (ii) the removed tumor stem cells, and (iii) the removed tumor degradation products.

21. The system according to claim 1, wherein the removed tumorous components include (i) the removed tumor cells, (ii) the removed tumor stem cells, and (iii) the removed tumor degradation products.

22. The system according to claim 1, further comprising the removed tumor component, wherein the removed tumor component comprises the removed tumor degradation product, and the removed tumor degradation product comprises a tumor exosomal peptide.

23. A method for preparing an autologous vaccine for a mammalian subject, wherein the method uses components of the subject's own exogenous blood and does not use surgically invasive biopsy of the subject. The aforementioned method, A step of positioning a cone-shaped coil upstream of a hemofiltration system, wherein the base of the cone-shaped coil is located at the widest part of the coil and is configured to receive the peristaltically flowing autologous plasma of the subject, and the coil is configured to inhibit hemolysis of the exogenous plasma by increasing the uniformity of the flow rate of the exogenous plasma output to the hemofiltration system; A step of filtering autologous exogenous plasma output from a cone-shaped coil or coil formed in a cone shape to remove oncogeneic components including at least one of tumor cells, tumor stem cells, and tumor degradation products, wherein the oncogeneic components are not recognized as antigens by the subject's immune system; A step of converting the removed tumor component into an antigen by directing electromagnetic radiation to it, such that each of the removed tumor cells, tumor stem cells, and tumor degradation products has a coagulated outer surface such that the removed tumor component can be recognized as an antigen by the immune system. Methods that include...

24. A step of filtering the autologous exogenous plasma output from the cone-shaped or cone-shaped coil by the hemofiltration system in order to remove a plurality of types of the tumorous components, wherein the plurality of types include at least two of tumor cells, tumor stem cells, and tumor degradation products, and none of the plurality of types contain tumorous components that are recognized as antigens by the subject's immune system. The steps include directing electromagnetic radiation to each of the at least two of the plurality of types of the removed tumorous component to convert each of the at least two of the plurality of types of the removed tumorous component into an antigen, so that each of the at least two of the removed tumorous cells, tumor stem cells, and tumor degradation products has a coagulated outer surface that can be recognized as the antigen by the immune system, The method according to claim 23, further comprising:

25. The method according to claim 23, further comprising the step of utilizing a peristaltic pump located upstream of the cone-shaped or cone-shaped coil, wherein the cone-shaped or cone-shaped coil is located upstream of the hemofiltration system and configured to receive the exogenous plasma flowing from the peristaltic pump.

26. The steps include placing a peristaltic pump downstream of the blood filtration system, The step of utilizing additional coils arranged or formed in a cone shape downstream of the pump, It further includes, The method according to claim 23, wherein the additional coil has a base at its widest portion and is configured to receive the exogenous plasma flowing from the pump and to inhibit hemolysis of the exogenous plasma by increasing the uniformity of the flow velocity of the exogenous plasma output from the pump.

27. The method according to claim 23, wherein the electromagnetic radiation has wavelengths in the ultraviolet (UV) range.

28. The method according to claim 23, wherein the UV irradiation includes at least two of UVA irradiation, UVB irradiation, and UVC irradiation, and the UVA irradiation, UVB irradiation, and UVC irradiation are provided separately.

29. The method according to claim 23, wherein the UV irradiation includes UVA irradiation, UVB irradiation, and UVC irradiation, each of which is applied separately.

30. The method according to claim 23, further comprising the step of irradiating at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products with electromagnetic radiation up to 0.1 terahertz.

31. The method according to claim 23, further comprising the step of applying hydrogenated water having a pH of about 8 to about 10 and an oxidation-reduction potential of about -400 to -800 mV to at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products.

32. The method according to claim 23, further comprising the step of freezing at least one of the removed tumor cells, removed tumor stem cells, and removed tumor degradation products for at least 5 minutes.

33. The method according to claim 23, further comprising injecting a subject with at least one of irradiated tumor cells, irradiated tumor stem cells, and irradiated tumor degradation products to cause the subject's immune system to produce antibodies in response to a coagulated outer surface.

34. The method according to claim 23, further comprising the step of filtering the plasma using a hemofiltration system including a multilayer rotatable filter, wherein each layer of the multilayer rotatable filter is configured according to tumor cells or tumor degradation products of different sizes.

35. The rotatable filter, The outer layer is configured to hold the tumor cells and has an opening of a first diameter, A second layer configured to hold the tumor stem cells and having an opening with a second diameter smaller than the first diameter, The method according to claim 34, having the following characteristics.

36. The aforementioned rotatable filter, The method according to claim 34, further comprising an inner layer configured to hold the tumor degradation product and having an opening of a third diameter smaller than the second diameter.

37. The rotatable filter, The outermost layer has an opening configured to hold the largest tumor cells, An inner layer having an opening configured to hold the second largest size tumor cell, An intermediate layer having an opening configured to hold tumor stem cells, An additional layer having openings configured to retain tumor degradation products, The method according to claim 36, including the method described in claim 36.

38. The method according to claim 23, wherein the neoplastic component comprises at least two of tumor cells, tumor stem cells, and tumor degradation products.

39. The method according to claim 37, wherein the tumor component comprises a tumor degradation product, and the tumor degradation product comprises a tumor exosomal peptide.

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