Method for recompiling immune system function by inducing immune resonance through heterologous antigen

Abstract

The invention provides a method for recompiling functions of an immune system by inducing immune resonance through a heterologous antigen, and belongs to the technical field of immunology and oncology. The method comprises the following steps: S1, screening specific heterologous antigens aiming at target tumor / cancer cells; s2, the screened heterologous antigen is modified to overcome immune escape of tumors / cancers or / and enhance immunogenicity of the tumors / cancers and change targeting of the tumors / cancers, and modification modes include but are not limited to carrier combination, chemical modification, adjuvant addition and the like; s3, delivering the modified heterologous antigen to a tumor / cancer pathogen site of a host or a microenvironment of the tumor / cancer pathogen site; and S4, monitoring the response of the host immune system to the heterologous antigen and the change condition of the tumor / cancer pathogen, and adjusting the dosage, the drug application frequency and the drug application mode of the heterologous antigen according to the monitoring result. According to the invention, by screening the specific heterologous antigen and carrying out modification treatment, the immunogenicity and the targeting property of the antigen are enhanced, and meanwhile, the treatment safety is evaluated and guaranteed.

Description

Technical Field

[0001] This invention provides a method for inducing immune resonance with heterologous antigens to reprogram the function of the immune system, belonging to the fields of immunology and oncology. Background Technology

[0002] Currently, the treatment of tumors / cancer-related diseases faces many challenges. Traditional treatments such as chemotherapy and radiotherapy often damage the patient's immune system and have limited efficacy. The immune system plays a crucial role in controlling tumors / cancer. How to effectively reprogram the immune system to overcome immune escape from tumors / cancer and reawaken its ability to recognize and eliminate tumors / cancer has become a hot research topic.

[0003] The body completes its metabolism through the replication and renewal of nucleic acid DNA, and gene mutations inevitably occur during this process due to changes in the body itself and / or the environment. These mutations are both a response to the environment and a source of species evolution. Most mutations are corrected under nucleic acid replication, cell proliferation, or immune regulation, but a few mutations escape regulation, leading to excessive cell growth and tumor formation, or slowing down and causing apoptosis. Over the past half-century, our pathological research on tumor formation and subsequent development into cancer has discovered a large number of tumor-specific antigens (TSA) or tumor-associated antigens (TAA), which has also confirmed that immune escape, resulting from immune desensitization or immune exhaustion (clonal selection) in response to immune regulation, leads to tumors and subsequently develops into cancer. However, most therapies targeting TSA / TAA are ineffective or even unsuccessful due to the body's immune escape from TSA / TAA.

[0004] To overcome immune evasion by tumors / cancer, we have invented immune resonance, which utilizes the expression of xenogeneic antigens (XA) on the surface of tumor / cancer cells to trigger a natural response from the body's immune system. This response reawakens the body's immune system to re-identify and process tumor / cancer cells (a reprogramming of the immune system) to achieve immune recognition, killing, and memory of tumors / cancer, thereby achieving specific and long-lasting therapeutic effects. This groundbreaking invention utilizes nucleic acid and / or protein drugs (nucleic acid drugs, protein drugs, or cell drugs) of xenogeneic antigens, expressed on tumor / cancer cells, to overcome the immune evasion of tumor / cancer cells from the patient's immune system, achieving specific and long-lasting therapeutic effects.

[0005] Because the expression of heterologous antigens (XA) on any tumor / cancer cell can trigger immune resonance, regardless of the tumor / cancer's own TSA / TAA, immune resonance technology has a broad spectrum of applications in tumor / cancer treatment. However, the immune resonance triggered by the expression of heterologous antigens (XA) on specific tumor / cancer cells is limited to those specific cells, thus immune resonance has high specificity and a narrow spectrum of applications in tumor / cancer treatment. Furthermore, because the immune memory induced by immune resonance is long-lasting, immune resonance treatment for tumors / cancer is long-term and has a long-lasting effect.

[0006] Based on the above, the inventors discovered that:

[0007] Heteroantigens, as antigenic substances from external sources, have the potential to stimulate an immune response in the body. However, existing immunotherapies for treating tumors / cancer have shortcomings in terms of immunogenicity, targeting, and safety, especially in overcoming immune escape, which limits their application in clinical treatment.

[0008] In view of this, research and improvement of existing therapies are proposed, and a method of inducing immune resonance by heterologous antigens to reprogram the immune system function is proposed to solve the above-mentioned problems. Summary of the Invention

[0009] This invention provides a method for inducing immune resonance with heterologous antigens to reprogram the function of the immune system, aiming to address the problems of low immunogenicity / immune escape, poor targeting, and insufficient safety in the treatment of tumors / cancer-related diseases.

[0010] To address the aforementioned problems, the present invention proposes the following technical solution: a method for inducing immune resonance with heterologous antigens to reprogram the function of the immune system, comprising the following steps:

[0011] S1. Screening for specific heterologous antigens targeting tumor / cancer cells, wherein the heterologous antigens may be selected from one or more of the following: pathogen antigens of infectious diseases, including viral antigens, functional heterologous antigens, cell surface marker antigens of other species, and artificially synthesized heterologous antigens.

[0012] S2. Modify the selected heterologous antigens to overcome immune escape from tumors / cancer and / or enhance their immunogenicity and change their targeting. Modification methods include, but are not limited to, binding with a carrier, chemical modification, and adding adjuvants.

[0013] S3. Deliver the modified heterologous antigen to the tumor / cancer pathogen site or its microenvironment in the host. Delivery methods include, but are not limited to, direct drug administration, drug administration via a drug delivery carrier, and direct drug administration to the surgical wound after surgery.

[0014] S4. Monitor the host's immune system response to foreign antigens and changes in tumor / cancer pathogens, and adjust the dosage, frequency, and method of administration of foreign antigens based on the monitoring results.

[0015] Furthermore, the cell surface antigens of other species include, but are not limited to, cell surface antigens of fish, rodents, birds, plants, fungi, bacteria, mycoplasma, and chlamydia.

[0016] Furthermore, the functional heteroantigens include intercellular adhesion molecules, activating or inhibiting proteins with certain activity, including but not limited to enzymes, hormones, cytokines, endocrine hormones, toxins, etc.

[0017] Furthermore, the drug delivery carrier includes liposomes (LNPs), viral vectors, modified messenger nucleic acid (mRNA) or short gene DNA fragments. During the drug delivery process, the host's physical condition is also assessed to determine the optimal timing and route of drug delivery.

[0018] Furthermore, the monitoring results include detecting the host's clinical indicators, including but not limited to the types, numbers, and activities of immune cells in the blood, the levels of cytokines, the content and changes of tumor markers, and examining the size and morphology of the tumor through imaging.

[0019] Furthermore, the adjustment of the dosage, frequency, and method of administration of the heterologous antigen is based on the intensity of the immune response and the control of the tumor / cancer pathogen in the monitoring results. When adjusting the dosage, frequency, and method of administration of the heterologous antigen, the host's age, sex, physical condition, and past medical history should also be considered.

[0020] Furthermore, this includes conducting safety assessments on heterologous antigens to ensure that they do not trigger severe adverse immune responses in the host.

[0021] Furthermore, the chemical modification includes one or more of the following modifications to the heterologous antigen: glycosylation, acetylation, and phosphorylation.

[0022] Furthermore, the adjuvant includes, but is not limited to, one or more of the following: protein, nucleic acid, lipid, aluminum adjuvant, oil emulsion adjuvant, and nucleic acid adjuvant.

[0023] Furthermore, the imaging examinations include one or more of CT scans, MRI scans, and PET-CT scans.

[0024] Due to the adoption of the above technical solution, the beneficial effects of the method of heterologous antigen-induced immune resonance to reprogram the immune system function in this invention are as follows:

[0025] 1. This invention enhances the immunogenicity and targeting of specific heterologous antigens by screening and modifying them, which can more effectively induce immune resonance and reprogram the immune system to reawaken immune recognition and memory of tumor / cancer cells.

[0026] 2. This invention improves the targetedness and long-term effectiveness of tumor / cancer treatment through reasonable delivery methods and monitoring and adjustment mechanisms, while also assessing and ensuring the safety of the treatment. This method provides a new and effective approach for the treatment of tumor / cancer-related diseases and has broad application prospects.

[0027] 3. This invention can be applied to the treatment of any tumor / cancer, and has a broad applicability to tumors / cancer. At the same time, it achieves its specificity and long-lasting effect by reprogramming the patient's immune system to generate specific recognition and memory of target tumor / cancer cells.

[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0029] Example 1: Treatment for Lung Cancer

[0030] Screening for heterologous antigens: Selecting specific antigens from different species as heterologous antigens for lung cancer.

[0031] Modification treatment: Nucleic acid modification and alteration of the selected heteroantigen genes to enhance their immunogenicity and targeting.

[0032] Delivery method: Liposomes (LNPs) are used as the drug delivery carrier to deliver the modified heterologous antigen to the lung tumor site in the patient. Before delivery, a comprehensive assessment of the patient's physical condition is conducted to determine the optimal timing and dosage for delivery.

[0033] Monitoring and Adjustment: Regularly monitor the types, numbers, and activities of immune cells, cytokine levels, and lung cancer tumor marker levels in the patient's blood. Simultaneously, monitor the size and morphology of the lung tumor using CT scans. Based on the monitoring results, if the immune response is weak and the tumor is not effectively controlled, appropriately adjust the dosage and frequency of the heterologous antigen; if the patient experiences mild discomfort, adjust the administration method to divided doses in small amounts. During the adjustment process, fully consider the patient's age, gender, physical condition, and past medical history.

[0034] Safety assessment: During treatment, the patient was closely monitored for adverse immune reactions such as fever and rash. Regular liver and kidney function tests were performed to ensure that the foreign antigen would not cause serious safety issues. After a period of treatment, the patient's lung tumor shrank, immune indicators improved, and no serious adverse reactions occurred.

[0035] Example 2: Treatment for Breast Cancer

[0036] Screening for heterologous antigens: Mouse cell surface marker antigens were selected as heterologous antigens for breast cancer.

[0037] Modification treatment: The murine antigen gene was modified and combined with an oil emulsion adjuvant to enhance its immunogenicity and targeting.

[0038] Delivery method: After surgical removal of breast cancer, the modified heterologous antigen is administered directly to the surgical wound, delivering it into the tumor microenvironment. The patient's postoperative recovery is assessed before administration to determine the appropriate timing.

[0039] Monitoring and Adjustment: Postoperatively, the types, activities, cytokine levels, and breast cancer tumor marker levels of relevant immune cells in the patient's blood are monitored regularly. Chest examination is also performed using MRI. Based on the monitoring results, if the immune response around the surgical wound is strong, the medication dosage is appropriately reduced; if signs of tumor recurrence are detected, the frequency of medication is increased. Adjustments are made based on the patient's individual circumstances.

[0040] Safety assessment: Observe the healing of the patient's surgical wound and check for adverse reactions such as infection and inflammation to ensure the safety of the treatment. After treatment, the patient's surgical wound healed well, no tumor recurrence was observed, and immune function was enhanced.

[0041] Example 3: Treatment for Liver Cancer

[0042] Screening for heterologous antigens: Selecting artificially synthesized heterologous antigens as therapeutic antigens for liver cancer.

[0043] Modification: Artificially synthesized antigen genes are modified to enhance their immunogenicity and targeting.

[0044] Delivery method: Modified messenger RNA is used as the drug delivery carrier to deliver the heterologous antigen to the patient's liver tumor site. Prior to delivery, the patient's liver function and other physical conditions are assessed to determine the optimal delivery route and dosage.

[0045] Monitoring and Adjustment: Regularly monitor the types and numbers of immune cells, cytokine levels, and liver cancer tumor marker levels in the patient's blood. Monitor changes in the liver tumor using PET-CT scans. Based on the monitoring results, if the immune response is moderate but the tumor shrinks slowly, adjust the medication frequency; if the patient's physical condition is poor, reduce the dose of the heterologous antigen. Adjustments should be made by comprehensively considering various factors related to the patient.

[0046] Safety assessment: Closely monitor the patient for any immune-related adverse reactions and regularly check liver function and other indicators. After treatment, the patient's liver cancer was controlled, immune function improved, and no serious safety events occurred.

[0047] The present invention and its embodiments have been described above. This description is not restrictive. In short, if a person skilled in the art is inspired by this description and designs a similar structure and embodiment without departing from the spirit of the present invention, such design should fall within the protection scope of the present invention.

Claims

1. A method for inducing immune resonance with heterologous antigens to reprogram the immune system, comprising the following steps: Includes the following steps: S1. Screening for specific heterologous antigens targeting tumor / cancer cells, wherein the heterologous antigens may be selected from one or more of the following: pathogen antigens of infectious diseases, including viral antigens, functional heterologous antigens, cell surface marker antigens of other species, and artificially synthesized heterologous antigens. S2. Modify the selected heterologous antigens to overcome immune escape from tumors / cancer and / or enhance their immunogenicity and change their targeting. Modification methods include, but are not limited to, binding with a carrier, chemical modification, and adding adjuvants. S3. Deliver the modified heterologous antigen to the tumor / cancer pathogen site or its microenvironment in the host. Delivery methods include, but are not limited to, direct drug administration, drug administration via a drug delivery carrier, and direct drug administration to the surgical wound after surgery. S4. Monitor the host's immune system response to foreign antigens and changes in tumor / cancer pathogens, and adjust the dosage, frequency, and method of administration of foreign antigens based on the monitoring results.

2. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The other species cell surface marker antigens include, but are not limited to, cell surface marker antigens of fish, rodents, birds, plants, fungi, bacteria, mycoplasma, and chlamydia.

3. The method for inducing immune resonance with heterologous antigens to reprogram the immune system function according to claim 1, characterized in that: The functional heteroantigens include intercellular adhesion molecules, activating or inhibiting proteins with certain activity, including but not limited to enzymes, hormones, cytokines, endocrine hormones, toxins, etc.

4. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The drug delivery carriers include liposomes (LNPs), viral vectors, modified messenger nucleic acid (mRNA) or short gene DNA fragments. During the drug delivery process, the host's physical condition is also assessed to determine the optimal timing and route of drug delivery.

5. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The monitoring results include detecting the host's clinical indicators, including but not limited to the types, numbers, and activities of immune cells in the blood, the levels of cytokines, the content and changes of tumor markers, and examining the size and morphology of the tumor through imaging.

6. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The adjustment of the dosage, frequency and method of administration of the heterologous antigen is based on the intensity of the immune response and the control of the tumor / cancer pathogen in the monitoring results. When adjusting the dosage, frequency and method of administration of the heterologous antigen, the host's age, sex, physical condition and past medical history should also be taken into account.

7. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: It also includes safety assessments of heterologous antigens to ensure that they do not trigger severe adverse immune responses in the host.

8. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The chemical modification includes one or more of the following: glycosylation, acetylation, and phosphorylation of the heterologous antigen.

9. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The adjuvants include, but are not limited to, one or more of the following: protein, nucleic acid, lipid, aluminum adjuvant, oil emulsion adjuvant, and nucleic acid adjuvant.

10. The method for inducing immune resonance with heterologous antigens to reprogram the immune system according to claim 1, characterized in that: The imaging examinations include one or more of CT scans, MRI scans, and PET-CT scans.