Anti-il1RL1 / il-33 / NF-kb antibody and method for treating acute myeloid leukemia using same

Abstract

An anti-IL1RL1 / IL-33 / NF-kB antibody and a method for treating acute myeloid leukemia using same. The anti-IL1RL1 / IL-33 / NF-kB antibody comprises an anti-IL1RL1 antibody, an anti-IL-33 antibody, and an anti-NF-kB antibody. The treatment method comprises: step 1, patient assessment and diagnosis; step 2, antibody selection and preparation; step 3, treatment plan formulation; step 4, antibody administration; step 5, efficacy monitoring and assessment; and step 6, subsequent treatment and follow-up. The combined use of the anti-IL1RL1 antibody, the anti-IL-33 antibody, and the anti-NF-kB antibody for treating AML can inhibit the proliferation and survival of AML cells at multiple levels by means of simultaneously blocking the IL-33 / IL1RL1 signaling pathway and NF-kB activation, thereby improving the therapeutic effect.

Description

Anti-il1rl1 / il-33 / nf-kb antibodies and methods of using the same to treat acute myeloid leukemia TECHNICAL FIELD

[0001] The present application relates to the technical field of acute myeloid leukemia treatment, in particular to anti-il1rl1 / il-33 / nf-kb antibodies and methods of using the same to treat acute myeloid leukemia. BACKGROUND

[0002] Acute myeloid leukemia (AML), also known as acute myelocytic leukemia, is a malignant disease originating from myeloid hematopoietic stem / progenitor cells. The clinical manifestations of patients with acute myeloid leukemia are diverse, mainly including anemia: pale complexion, fatigue, dizziness and even dyspnea, etc.; bleeding: petechiae, ecchymoses, gum bleeding, nasal bleeding, etc.; intracranial hemorrhage can be fatal, and disseminated intravascular coagulation may occur in the late stage; infection: patients are prone to infection due to lack of granulocytes, and the infection site may involve the upper respiratory tract, lungs, oral cavity, perianal and whole body (sepsis), etc.; organ infiltration: lymph node and liver and spleen enlargement (but splenomegaly is relatively rare), bone and joint pain (sternal tenderness is a common sign), and testicular enlargement and other extramedullary relapse manifestations; in addition, chloroma (localized infiltration of abnormal white blood cells under the periosteum or in soft tissue) may also occur.

[0003] The existing acute myeloid leukemia treatment method has the following defects: first, AML cells are not sensitive enough to most chemotherapy drugs; this means that even with high-intensity chemotherapy intervention, it is difficult to ensure the effective elimination of AML cells, thereby affecting the overall effect of treatment and the prognosis of patients; this characteristic increases the risk of disease recurrence, making the treatment process more complex and difficult; second, AML cells exhibit high drug resistance, and some AML cells can resist chemotherapy drugs through various mechanisms such as increased drug pumping out, enhanced DNA repair ability, or inhibition of the apoptosis pathway, forming a so-called drug resistance phenomenon; the existence of this drug resistance not only limits the effectiveness of chemotherapy drugs, but also further exacerbates the difficulty and uncertainty of treatment; third, antibody therapy as a new emerging treatment method has achieved preliminary results in the treatment of some types of leukemia, but its application in AML is faced with the problem of insufficient targeting; due to the high heterogeneity of AML cells and the complex and variable expression of surface markers, antibody therapy is difficult to accurately distinguish AML cells from normal blood cells, thereby inevitably causing damage to normal cells during the treatment process, leading to a series of serious side effects. SUMMARY

[0004] The present application aims to provide anti-IL1RL1 / IL-33 / NF-kB antibodies and methods for treating acute myeloid leukemia using the same to solve the problems raised in the background.

[0005] To achieve the above-mentioned purpose, the present application provides the following technical solutions: Anti-IL1RL1 / IL-33 / NF-kB antibodies, comprising: anti-IL1RL1 antibodies, anti-IL-33 antibodies and anti-NF-kB antibodies, the anti-IL1RL1 antibodies are specific receptors of interleukin-33 (IL-33), which function to block the binding of IL-33 to IL1RL1, thereby inhibiting IL-33-mediated signal transduction, and in AML treatment, by blocking the IL-33 / IL1RL1 signaling pathway, cell proliferation can be inhibited, cell apoptosis can be promoted, and drug sensitivity can be enhanced.

[0006] As a further technical solution of the present application: the anti-IL-33 antibody is an IL-1-like cytokine with a wide range of biological effects, which functions to prevent its binding to the receptor IL1RL1, thereby inhibiting the activation of the downstream signaling pathway, and in AML treatment, the anti-IL-33 antibody can be used to block IL-33-mediated NF-κB activation and AKT phosphorylation, thereby inhibiting cell survival and drug resistance.

[0007] As a further technical solution of the present application: the anti-NF-kB antibody, as a key transcription factor, is involved in various cellular processes, including proliferation, apoptosis and inflammatory response, which functions to directly inhibit the activity of NF-κB, prevent it from entering the nucleus and regulate the expression of target genes, and in AML treatment, the anti-NF-kB antibody can be used to block IL-33-induced NF-κB activation, thereby inhibiting the activation of the downstream signaling pathway, such as the production of IL-6 and the phosphorylation of AKT.

[0008] The method for treating acute myeloid leukemia using anti-IL1RL1 / IL-33 / NF-kB antibodies comprises the following steps: step one, patient evaluation and diagnosis; step two, antibody selection and preparation; step three, treatment plan development; step four, antibody administration; step five, efficacy monitoring and evaluation; step six, follow-up treatment and follow-up;

[0009] In the above step one, the overall health status of the patient is comprehensively evaluated to determine the stage and type of the disease;

[0010] In the above step two, according to the specific condition of the patient and the treatment plan, the appropriate anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody are selected;

[0011] In the above step three, according to the specific condition of the patient, the physical condition and the characteristics of the antibody, a detailed treatment plan is developed;

[0012] Among them, in the above step four, according to the treatment plan, the selected antibody is administered to the patient through an appropriate route;

[0013] Among them, in the above step five, during the treatment, the patient's condition changes are monitored regularly, and the patient's possible side effects and adverse reactions are concerned;

[0014] Among them, in the above step six, according to the patient's treatment effect and condition change, the subsequent treatment plan is made, and the regular follow-up and review are arranged.

[0015] As a further technical solution of the present application: in the step one, the overall health status of the patient is comprehensively and deeply evaluated, including detailed inquiry of the patient's medical history, family history, and comprehensive physical examination, blood test, bone marrow test, imaging examination means are used to determine the stage and type of AML, the stage is usually based on the proportion of leukemia cells in the bone marrow, whether it has spread to other organs and other factors; and the type is based on the genetic and molecular characteristics of leukemia cells, this process is crucial for the subsequent treatment plan, which helps to understand the severity of the disease, the possible development trend, and the patient's potential response to a specific treatment.

[0016] As a further technical solution of the present application: in the step two, according to the patient's specific condition and treatment goal, the appropriate anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody are selected, and various factors need to be considered in the selection process, including the specificity, potency, side effects of the antibody, and the patient's possible allergy history, to ensure that the antibody is in the best state, including the correct storage temperature, to avoid contamination and expired use, to ensure its treatment effect and safety.

[0017] As a further technical solution of the present application: in the step three, according to the patient's specific condition, physical condition and the characteristics of the selected antibody, a detailed treatment plan is made, including the goal of treatment, the expected course of treatment, the administration mode, the dose and the frequency of the antibody, in addition to considering the possible side effects and adverse reactions encountered by the patient, and making corresponding prevention and response measures, the treatment plan ensures the effectiveness and safety of the treatment.

[0018] As a further technical solution of the present application: in the step four, according to the treatment plan, the selected antibody is administered to the patient through an appropriate route, the administration process needs to strictly follow the aseptic operation principle to ensure the purity and safety of the drug, in the administration process, the patient's vital signs and reactions are closely monitored to discover and handle any possible abnormal situation in time, after the administration is completed, the patient is closely observed to ensure that the drug can exert the expected therapeutic effect.

[0019] As a further technical solution of the present application: in step five, during the treatment process, the patient's condition changes are regularly monitored to evaluate the effectiveness of the treatment, including checking the patient's blood indicators, bone marrow image, and conducting necessary imaging examinations. Through these examinations, it can be understood whether the number of leukemia cells in the patient is reduced, whether the symptoms are improved, and whether new lesions appear. At the same time, attention should be paid to possible side effects and adverse reactions of the patient, such as allergic reactions, infections and bleeding, and appropriate treatment measures should be taken in time. Treatment monitoring and evaluation are important links to ensure the effectiveness and safety of treatment.

[0020] As a further technical solution of the present application: in step six, according to the treatment effect and condition changes of the patient, a follow-up treatment plan is developed. If the treatment effect is significant and the patient's symptoms have improved significantly, the current treatment regimen will be continued or the dosage and administration frequency will be appropriately adjusted. If the treatment effect is not good or the patient has relapsed, etc., the medical team will re-evaluate the patient's condition and consider using other treatment methods or combined treatment regimens. Regular follow-up and review will be arranged to monitor the patient's condition changes and timely discover and handle any new problems. The frequency of follow-up and review will be determined according to the specific circumstances of the patient to ensure that the patient can receive timely and effective treatment.

[0021] Compared with the prior art, the present application has the following beneficial effects: the present application combines anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody for treating AML, realizing a new strategy of multi-target point synergistic treatment. By simultaneously blocking the IL-33 / IL1RL1 signaling pathway and the activation of NF-kB, the proliferation and survival of AML cells can be inhibited from multiple aspects, significantly reducing the survival ability of AML cells and improving the treatment effect. By precisely blocking the combination of IL-33 and IL1RL1 through anti-IL1RL1 antibody, the signal transduction process mediated by IL-33 is effectively inhibited, thereby inhibiting the proliferation ability of AML cells and promoting their apoptosis. At the same time, the sensitivity of AML cells to chemotherapeutic drugs is also significantly enhanced, thereby further improving the treatment effect. By inhibiting the activation of NF-κB and AKT phosphorylation through anti-IL-33 antibody and anti-NF-kB antibody, the drug resistance of AML cells can be reduced, avoiding the occurrence of drug resistance. Since the antibody can accurately recognize and bind to specific antigens on the surface of AML cells, the damage to normal cells can be minimized, thereby greatly reducing the side effects of treatment. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 is a flowchart of the method of the present application. DETAILED DESCRIPTION

[0023] With reference to the accompanying drawings: the technical solutions in the embodiments of the present application will be apparently and completely described, obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor belong to the scope of protection of the present application.

[0024] Please refer to FIG. 1, an embodiment provided by the present application: an anti-IL1RL1 / IL-33 / NF-kB antibody, including: an anti-IL1RL1 antibody, an anti-IL-33 antibody and an anti-NF-kB antibody, the anti-IL1RL1 antibody is a specific receptor of interleukin-33 (IL-33), its function is to block the binding of IL-33 and IL1RL1, thereby inhibiting IL-33-mediated signal transduction, in the treatment of AML, by blocking the IL-33 / IL1RL1 signaling pathway, it can inhibit cell proliferation, promote apoptosis, and enhance drug sensitivity; the anti-IL-33 antibody is an IL-1-like cytokine with a wide range of biological effects, its function is to prevent its binding to the receptor IL1RL1, thereby inhibiting the activation of the downstream signaling pathway, in the treatment of AML, the anti-IL-33 antibody can be used to block IL-33-mediated NF-κB activation and AKT phosphorylation, thereby inhibiting cell survival and the generation of drug resistance; the anti-NF-kB antibody is a key transcription factor, which is involved in various cellular processes, including proliferation, apoptosis and inflammatory response, its function is to directly inhibit the activity of NF-κB, prevent it from entering the nucleus and regulate the expression of target genes, in the treatment of AML, the anti-NF-kB antibody can be used to block IL-33-induced NF-κB activation, thereby inhibiting the activation of the downstream signaling pathway, such as the production of IL-6 and the phosphorylation of AKT.

[0025] The method for treating acute myeloid leukemia using anti-IL1RL1 / IL-33 / NF-kB antibody, including step one, patient evaluation and diagnosis; step two, antibody selection and preparation; step three, treatment plan development; step four, antibody administration; step five, efficacy monitoring and evaluation; step six, follow-up treatment and follow-up;

[0026] Among them, in the above step one, the overall health status of the patient is comprehensively and deeply evaluated, including detailed inquiry of the patient's medical history, family medical history, and comprehensive physical examination, using blood test, bone marrow test, imaging examination means, to determine the stage and type of AML, the stage is usually based on the proportion of leukemia cells in the bone marrow, whether it has spread to other organs and other factors; while the type is based on the genetic and molecular characteristics of leukemia cells, this process is crucial for the subsequent development of treatment plan, which helps to understand the severity of the disease, the possible development trend, and the potential response of the patient to a specific treatment;

[0027] Among the above step two, according to the specific condition of the patient and the treatment target, the appropriate anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody is selected, and the selection process needs to consider various factors, including the specificity, potency, side effects of the antibody, and the patient's possible allergy history, to ensure that the antibody is in the best state, including the correct storage temperature, avoid contamination and expired use, to ensure its therapeutic effect and safety;

[0028] Among the above step three, according to the specific condition of the patient, physical condition and the characteristics of the selected antibody, a detailed treatment plan is developed, including the target of treatment, the expected course of treatment, the administration mode, dosage and frequency of the antibody, in addition to considering the side effects and adverse reactions that the patient may encounter, and developing corresponding prevention and response measures, the development of treatment plan ensures the effectiveness and safety of treatment;

[0029] Among the above step four, according to the treatment plan, the selected antibody is administered to the patient through appropriate routes, the administration process needs to strictly follow the aseptic operation principle to ensure the purity and safety of the drug, and in the administration process, the patient's vital signs and reactions are closely monitored to discover and handle any abnormal situations in time, and after the administration is completed, the patient is closely observed to ensure that the drug can exert the expected therapeutic effect;

[0030] Among the above step five, during the treatment, the patient's condition changes are monitored regularly to evaluate the effectiveness of the treatment, including checking the patient's blood indicators, bone marrow image, and conducting necessary imaging examinations, through these examinations, it can be known whether the patient's leukemia cell count is reduced, the symptoms are improved, and whether new lesions appear, at the same time, the patient's possible side effects and adverse reactions, such as allergic reactions, infections and bleeding, are concerned, and appropriate handling measures are taken in time, the efficacy monitoring and evaluation are important links to ensure the effectiveness and safety of treatment;

[0031] Among the above step six, according to the patient's treatment effect and condition change, the subsequent treatment plan is developed, if the treatment effect is significant and the patient's symptoms are significantly improved, the current treatment plan is continued or the dosage and administration frequency are appropriately adjusted, if the treatment effect is not good or the patient has recurrence, etc., the medical team will re-evaluate the patient's condition and consider using other treatment methods or combined treatment plan, arrange regular follow-up and review to monitor the patient's condition changes, and timely discover and handle any new problems, the frequency of follow-up and review will be determined according to the patient's specific situation, to ensure that the patient can receive timely and effective treatment.

[0032] Based on the above, the advantages of the present application are that the present application proposes a new strategy of applying anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-κB antibody to acute myeloid leukemia treatment, which marks a major progress of multi-target point synergistic therapy in the field of AML, and by simultaneously acting on the two key biological processes of IL-33 / IL1RL1 signal pathway and NF-κB activation, the present application can comprehensively inhibit the proliferation activity and survival ability of AML cells from multiple dimensions and aspects, thereby significantly improving the treatment effect, specifically, the anti-IL1RL1 antibody precisely blocks the interaction between IL-33 and IL1RL1 with high specificity and affinity, which effectively inhibits the signal transduction pathway mediated by IL-33, thereby significantly inhibiting the abnormal proliferation of AML cells and inducing them to enter the apoptosis program, and also exhibits the ability to enhance the sensitivity of AML cells to chemotherapeutic drugs, so that traditional chemotherapeutic drugs can more effectively exert their killing effect, thereby further improving the overall treatment effect, while the anti-IL-33 antibody and the anti-NF-κB antibody synergistically inhibit the activation of NF-κB and the downstream AKT phosphorylation process, which not only weakens the drug resistance mechanism of AML cells, but also significantly reduces the occurrence of drug resistance, so that AML cells are more vulnerable when facing chemotherapeutic drugs, thereby improving the success rate of treatment, and more importantly, since antibody therapy has high targeting ability, it can accurately recognize and bind to specific antigens on the surface of AML cells, thereby minimizing non-specific damage to normal cells, which greatly reduces the side effects of treatment, so that patients can maintain a high quality of life during treatment, reducing discomfort and pain caused by treatment, and in summary, the multi-target point synergistic therapy strategy proposed in the present application not only significantly improves the treatment effect of AML, but also maximally reduces the side effects of treatment, providing a safer and more effective treatment for AML patients.

[0033] It will be apparent to those skilled in the art that the present application is not limited to the details of the above exemplary embodiments, but can be implemented in other specific forms without departing from the spirit or essential characteristics of the present application. Therefore, the embodiments should be considered in all aspects as exemplary and non-limiting, and the scope of the present application is defined by the appended claims rather than the above description, and it is intended to encompass all changes falling within the meaning and scope of the equivalent elements of the claims. Any reference signs in the claims should not be considered as limiting the claims involved.

Claims

1. Anti-IL1RL1 / IL-33 / NF-kB antibodies, comprising: Anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody, characterized in that: the anti-IL1RL1 antibody is a specific receptor of interleukin-33 (IL-33), which functions to block the binding of IL-33 to IL1RL1, thereby inhibiting IL-33-mediated signal transduction, and by blocking the IL-33 / IL1RL1 signaling pathway, it is possible to inhibit cell proliferation, promote apoptosis, and enhance drug sensitivity in the treatment of AML.

2. The anti-ILlRLl / IL-33 / NF-kB antibody of claim 1, wherein: The anti-IL-33 antibody is an IL-1-like cytokine with a wide range of biological effects, which functions to prevent its binding to the receptor IL1RL1, thereby inhibiting the activation of the downstream signaling pathway, and in the treatment of AML, the anti-IL-33 antibody can be used to block IL-33-mediated NF-κB activation and AKT phosphorylation, thereby inhibiting cell survival and the development of drug resistance.

3. The anti-ILlRLl / IL-33 / NF-kB antibody of claim 1, wherein: The anti-NF-kB antibody is a key transcription factor involved in various cellular processes, including proliferation, apoptosis, and inflammatory response, which functions to directly inhibit the activity of NF-κB, prevent its entry into the nucleus and regulate the expression of target genes, and in the treatment of AML, the anti-NF-kB antibody can be used to block IL-33-induced NF-κB activation, thereby inhibiting the activation of the downstream signaling pathway, such as the production of IL-6 and the phosphorylation of AKT.

4. A method for treating acute myeloid leukemia using anti-IL1RL1 / IL-33 / NF-kB antibodies, comprising the steps of: step one, patient evaluation and diagnosis; step two, antibody selection and preparation; step three, treatment plan development; step four, antibody administration; step five, efficacy monitoring and evaluation; step six, follow-up treatment and follow-up; characterized in that: In the above step one, the overall health status of the patient is comprehensively evaluated to determine the stage and type of the disease; In the above step two, according to the specific condition of the patient and the treatment plan, the appropriate anti-IL1RL1 antibody, anti-IL-33 antibody and anti-NF-kB antibody are selected; In the above step three, according to the specific condition of the patient, the physical condition and the characteristics of the antibody, a detailed treatment plan is developed; In the above step four, according to the treatment plan, the selected antibody is administered to the patient through an appropriate route; In the above step five, during the treatment process, the patient's condition changes are monitored regularly, and the possible side effects and adverse reactions of the patient are concerned; In the above step six, according to the treatment effect and condition change of the patient, the subsequent treatment plan is developed, and the regular follow-up and review are arranged.

5. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies according to claim 4, characterized in that: In step one, a comprehensive and in-depth assessment of the patient's overall health is conducted, including detailed inquiry of the patient's medical history, family history, and a thorough physical examination. Blood tests, bone marrow tests, and imaging tests are used to determine the stage and type of AML. The stage is usually based on the proportion of leukemia cells in the bone marrow, whether it has spread to other organs, etc. The type is based on the genetic and molecular characteristics of leukemia cells. This process is crucial for subsequent treatment plan development, helping to understand the severity of the disease, possible development trends, and the patient's potential response to specific treatments.

6. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies of claim 4, wherein: In step two, appropriate anti-IL1RL1 antibodies, anti-IL-33 antibodies, and anti-NF-kB antibodies are selected based on the patient's specific condition and treatment goals. The selection process needs to consider various factors, including the specificity, efficacy, side effects of the antibodies, and the patient's possible allergy history, to ensure that the antibodies are in the best condition, including the correct storage temperature, avoiding contamination, and avoiding expired use, to ensure their therapeutic effect and safety.

7. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies of claim 4, wherein: In step three, a detailed treatment plan is developed based on the patient's specific condition, physical condition, and the characteristics of the selected antibodies, including the treatment goals, expected course of treatment, antibody administration method, dosage, and administration frequency. In addition, possible side effects and adverse reactions encountered by the patient are considered, and corresponding prevention and response measures are developed. The development of the treatment plan ensures the effectiveness and safety of the treatment.

8. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies of claim 4, characterized in that: In step four, the selected antibodies are administered to the patient through appropriate routes according to the treatment plan. The administration process needs to strictly follow the principles of aseptic operation to ensure the purity and safety of the drugs. During the administration process, the patient's vital signs and reactions are closely monitored to detect and handle any abnormalities that may arise. After the administration is completed, the patient is closely observed to ensure that the drugs can exert the expected therapeutic effect.

9. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies of claim 4, characterized in that: In step five, during the treatment process, the patient's condition is regularly monitored to evaluate the effectiveness of the treatment, including checking the patient's blood indicators, bone marrow image, and performing necessary imaging tests. Through these tests, it can be determined whether the patient's leukemia cell count has decreased, symptoms have improved, and whether new lesions have appeared. At the same time, attention is paid to possible side effects and adverse reactions such as allergic reactions, infections, and bleeding, and appropriate handling measures are taken in a timely manner. Treatment monitoring and evaluation are important steps to ensure the effectiveness and safety of treatment.

10. The method of treating acute myeloid leukemia with anti-IL1RL1 / IL-33 / NF-kB antibodies of claim 4, characterized in that: In step six, based on the patient's treatment effect and condition changes, subsequent treatment plans are developed. If the treatment effect is significant and the patient's symptoms have improved significantly, the current treatment plan is continued or the dosage and administration frequency are appropriately adjusted. If the treatment effect is not satisfactory or the patient has relapsed, etc., the medical team will re-evaluate the patient's condition and consider using other treatment methods or combined treatment plans. Regular follow-up and review are arranged to monitor the patient's condition changes and timely detect and handle any new problems. The frequency of follow-up and review will be determined based on the patient's specific situation to ensure that the patient can receive timely and effective treatment.

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