Application method and system of tumor effect B cells in colorectal cancer liver metastasis

Abstract

The invention belongs to the technical field of medicine, and discloses an application method of tumor-killing effect B cells in colorectal cancer liver metastasis, Meta-CBL is used for transforming the B cells into tumor-killing effect cells for the first time, and the anti-tumor immune effect is remarkably enhanced. In a tumor microenvironment, the meta-CBL can directly kill tumor cells and activate other effector immune cells, so that synergistic anti-tumor is realized. By combining liquid biopsy and single cell sequencing, tumor load and microenvironment immune state can be tracked in real time. The evaluation precision is higher than that of traditional iconography, invalid treatment patients can be recognized in the early stage, and the treatment strategy is adjusted in time. Precise treatment and dynamic prognosis evaluation of colorectal cancer liver metastasis are realized by innovatively utilizing meta-CBL, and the defects of limited treatment effect and lagging evaluation means in the prior art are overcome. The comprehensive system structure and the precise treatment strategy of the system bring brand new treatment choices and remarkable survival benefits for patients with colorectal cancer liver metastasis, and the system has extremely high industrialization and clinical popularization value.

Description

Technical Field

[0001] This invention belongs to the field of medical technology, and in particular relates to a method and system for the application of tumor-killing B cells in liver metastases of colorectal cancer. Background Technology

[0002] Colorectal cancer liver metastases (CRLM) are one of the leading causes of death in colorectal cancer (CRC) patients. Current treatments include surgical resection, radiotherapy, chemotherapy, and targeted therapy, but their efficacy is limited and side effects are significant. In recent years, immunotherapy (such as immune checkpoint inhibitors) has shown some potential; however, in colorectal cancer liver metastases, the complexity of the tumor microenvironment and its immunosuppressive properties result in low patient response rates. Furthermore, tumor prognostic assessment relies on traditional imaging and biomarkers, making it difficult to dynamically reflect treatment efficacy.

[0003] Based on the above analysis, the problems and shortcomings of the existing technology are as follows:

[0004] (1) Treatment challenge: How to effectively activate the anti-tumor immune response in the tumor microenvironment and improve the tumor killing effect.

[0005] (2) Inadequate prognostic assessment: How to assess the treatment effect of colorectal cancer liver metastasis in a real-time, dynamic and accurate manner.

[0006] (3) Lack of personalized treatment strategies: How to develop precise personalized immunotherapy strategies based on the specific tumor characteristics of patients. Summary of the Invention

[0007] To address the problems existing in the prior art, this invention provides a method for applying tumor-killing effector B cells in colorectal cancer liver metastases.

[0008] This invention is implemented as follows: a method for applying tumor-killing effector B cells in colorectal cancer liver metastases includes:

[0009] Step 1, preparation and loading of meta-CBL;

[0010] B cells were extracted from the patient's peripheral blood and modified using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines.

[0011] Meta-CBL was amplified in an in vitro culture system and loaded into a targeted delivery system via a specific delivery vector.

[0012] Step 2, Immune remodeling of the tumor microenvironment;

[0013] The loaded meta-CBL is delivered to the tumor site via local injection or hepatic artery perfusion to perform the following functions:

[0014] It secretes pro-inflammatory factors and activates the anti-tumor activity of CD8+ T cells and natural killer cells;

[0015] Neutralize immunosuppressive factors in the tumor microenvironment;

[0016] It works synergistically with tumor antigen-specific cytokines to promote the direct killing of tumor cells;

[0017] Step 3, real-time prognostic assessment;

[0018] Circulating tumor DNA and exosomes were collected from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden;

[0019] By combining single-cell sequencing technology, the distribution, activity and action pathway of meta-CBL in the tumor microenvironment were analyzed, and a high-resolution immune response map was obtained.

[0020] Step 4, Intelligent Feedback and Optimization;

[0021] The collected data is uploaded to the AI ​​analysis platform, and machine learning models are used to conduct multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerance, and the extent of prognostic improvement.

[0022] Based on AI feedback, the dosage and delivery strategy of meta-CBL are optimized to customize personalized treatment plans for patients.

[0023] Furthermore, the preparation and loading of the meta-CBL:

[0024] Cell sorting system:

[0025] B cells were isolated from the patient's peripheral blood and high-purity B cells were obtained using flow cytometry.

[0026] After sorting, B cells are stored in a sterile environment to ensure cell viability and purity for subsequent operations.

[0027] Gene transfection instrument:

[0028] Tumor antigen-specific receptor gene fragments are introduced into B cells using electroporation or viral vectors.

[0029] At the same time, gene editing technology can be used to give B cells the ability to secrete specific immunomodulatory factors, such as IFN-γ and IL-12.

[0030] In vitro culture device:

[0031] The transfected B cells were transferred to a dynamic culture device to provide suitable growth conditions;

[0032] Adding growth factors and supplementing nutrients promotes the expansion and functional differentiation of meta-CBLs;

[0033] The amplified meta-CBL was aliquoted using a cryopreservation device and prepared for treatment.

[0034] Furthermore, the immune remodeling of the tumor microenvironment:

[0035] Local drug delivery system:

[0036] meta-CBL is encapsulated via nanocarriers or liposome delivery systems to protect cells from attack by the body's immune system;

[0037] Using microinfusion pumps or hepatic artery perfusion technology, meta-CBL can be precisely delivered to the tumor site, ensuring efficient delivery to liver metastases.

[0038] Microenvironment monitoring sensors:

[0039] Microsensors are implanted at the tumor site to monitor the concentration of immune factors and metabolic indicators in the tumor microenvironment in real time.

[0040] The sensor transmits the monitoring results to the central processing unit in real time via wireless data transmission to determine the activity of meta-CBL in the tumor microenvironment;

[0041] Immune microenvironment remodeling:

[0042] meta-CBL activates the anti-tumor activity of CD8+ T cells and natural killer cells by secreting pro-inflammatory cytokines;

[0043] Meanwhile, the factors released by meta-CBL inhibit immunosuppressive cells and enhance the overall anti-tumor immune response.

[0044] Furthermore, the real-time prognostic assessment:

[0045] Circulating tumor DNA detection platform:

[0046] ctDNA is isolated from the patient's blood using liquid biopsy technology;

[0047] The abundance of specific mutation sites in ctDNA can be detected using fluorescent PCR or digital PCR techniques to assess changes in tumor burden.

[0048] Single-cell sequencing equipment:

[0049] Meta-CBL and tumor cell samples were extracted from tumor tissue or blood and single-cell sequencing was performed.

[0050] The distribution, activity, and interactions of meta-CBL with other cells in the tumor microenvironment were analyzed.

[0051] Generate dynamic maps of the tumor immune microenvironment for precise evaluation of treatment efficacy;

[0052] Results integration and dynamic feedback:

[0053] The test data is uploaded to the cloud via a data interface, and combined with the patient's historical data, the treatment efficiency of meta-CBL is dynamically evaluated;

[0054] Adjust the dosage or delivery strategy of meta-CBL based on the results.

[0055] Furthermore, the intelligent feedback and optimization:

[0056] Data acquisition terminal:

[0057] Data is collected in real time from microenvironment sensors, liquid biopsy platforms, and single-cell sequencing equipment;

[0058] The data included immune factor concentrations, changes in tumor burden, and the distribution and activity of meta-CBLs.

[0059] AI analytics platform:

[0060] Utilize deep learning models to analyze and model the collected data;

[0061] Generate multidimensional analysis results, including dynamic changes in tumor burden, meta-CBL activity heatmap, and immune response curve;

[0062] Predict the short-term and long-term effects of treatment and identify potential risk factors;

[0063] Cloud storage and feedback system.

[0064] Furthermore, the cloud storage and feedback system:

[0065] All data is uploaded to a cloud platform for comparative analysis with a global gene database to search for new tumor markers and immune response mechanisms;

[0066] Based on the analysis results, the system provides clinicians with treatment optimization suggestions, including dose adjustment, meta-CBL reloading, or combination with other immunotherapy regimens.

[0067] Another object of the present invention is to provide a system for the application of tumor-killing B cells in colorectal cancer liver metastases, comprising:

[0068] The preparation and loading module is used to extract B cells from the patient's peripheral blood, modify the B cells using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines, amplify meta-CBL in an in vitro culture system, and load it into a targeted delivery system through a specific delivery vector;

[0069] The tumor microenvironment regulation module is used to deliver the loaded meta-CBL to the tumor site via local injection or hepatic artery perfusion, and performs the following functions: secreting pro-inflammatory factors, activating the anti-tumor activity of CD8+ T cells and natural killer cells; neutralizing immunosuppressive factors in the tumor microenvironment; and synergistically acting with tumor antigen-specific cytokines to promote the direct killing of tumor cells.

[0070] The prognostic assessment module is used to collect circulating tumor DNA and exosomes from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden; combined with single-cell sequencing technology, it analyzes the distribution, activity, and pathway of meta-CBL in the tumor microenvironment and obtains high-resolution immune response maps.

[0071] The intelligent analysis and feedback module is used to upload the collected data to the AI ​​analysis platform and use machine learning models to perform multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerability, and the extent of prognostic improvement. Based on AI feedback, the meta-CBL dosage and delivery strategy are optimized to customize personalized treatment plans for patients.

[0072] Another object of the present invention is to provide a computer device comprising a memory and a processor, the memory storing a computer program, which, when executed by the processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases.

[0073] Another object of the present invention is to provide a computer-readable storage medium storing a computer program, which, when executed by a processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases.

[0074] Another objective of this invention is to provide an information data processing terminal, which is used to realize the application system of tumor-killing effect B cells in colorectal cancer liver metastases.

[0075] Based on the above technical solutions and the technical problems solved, the advantages and positive effects of the technical solution to be protected by this invention are as follows:

[0076] The working principle of each module achieves efficient collaboration through the combination of hardware and software. The meta-CBL preparation and loading module ensures the preparation of high-quality tumor-killing cells; the tumor microenvironment regulation module optimizes the local immune microenvironment; the prognostic assessment module enables real-time, dynamic monitoring of treatment effects; and the intelligent analysis and feedback module provides precise suggestions for personalized treatment. This system can significantly improve treatment outcomes while reducing treatment risks, propelling the treatment of colorectal cancer liver metastases into the era of precision immunotherapy.

[0077] 1. Breakthrough in treatment challenges

[0078] meta-CBL is the first technology to transform B cells into tumor-killing effector cells, significantly enhancing anti-tumor immune effects.

[0079] In the tumor microenvironment, meta-CBL can directly kill tumor cells and activate other effector immune cells, achieving synergistic anti-tumor effects.

[0080] 2. Real-time dynamic prognostic assessment

[0081] The combination of liquid biopsy and single-cell sequencing enables real-time tracking of tumor burden and microenvironmental immune status.

[0082] The assessment accuracy is higher than that of traditional imaging, enabling early identification of patients who do not respond to treatment and timely adjustment of treatment strategies.

[0083] 3. Realization of Personalized Treatment

[0084] By using patients' tumor-specific antigen information, personalized meta-CBLs can be designed to significantly improve treatment targeting.

[0085] By combining AI platform analysis, treatment plans can be optimized, adverse reactions reduced, and patient tolerance improved.

[0086] 4. Significant clinical efficacy

[0087] In animal models, meta-CBL significantly inhibited the growth of liver metastases, with a tumor shrinkage rate of over 70%.

[0088] Clinical trial results showed that patients' overall survival (OS) and progression-free survival (PFS) were significantly prolonged.

[0089] This technology innovatively utilizes meta-CBL to achieve precise treatment and dynamic prognostic assessment of colorectal cancer liver metastases, overcoming the limitations of existing technologies in terms of limited treatment efficacy and outdated assessment methods. Its comprehensive system structure and precise treatment strategy bring new treatment options and significant survival benefits to patients with colorectal cancer liver metastases, possessing extremely high industrialization and clinical application value. Attached Figure Description

[0090] Figure 1 This is a flowchart illustrating the application of tumor-killing B cells in colorectal cancer liver metastases, as provided in this embodiment of the invention.

[0091] Figure 2 This is a flowchart of the real-time prognostic assessment method provided in the embodiments of the present invention.

[0092] Figure 3 This is a block diagram of the system structure for the application of tumor-killing B cells in colorectal cancer liver metastases, as provided in an embodiment of the present invention. Detailed Implementation

[0093] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0094] like Figure 1 As shown, the application method of tumor-killing effector B cells in colorectal cancer liver metastases provided by this embodiment of the invention includes the following steps:

[0095] S101, preparation and loading of meta-CBL;

[0096] B cells were extracted from the patient's peripheral blood and modified using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines.

[0097] Meta-CBL was amplified in an in vitro culture system and loaded into a targeted delivery system via a specific delivery vector.

[0098] S102, immune remodeling of the tumor microenvironment;

[0099] The loaded meta-CBL is delivered to the tumor site via local injection or hepatic artery perfusion to perform the following functions:

[0100] It secretes pro-inflammatory factors and activates the anti-tumor activity of CD8+ T cells and natural killer cells;

[0101] Neutralize immunosuppressive factors in the tumor microenvironment;

[0102] It works synergistically with tumor antigen-specific cytokines to promote the direct killing of tumor cells;

[0103] S103, Real-time Prognostic Assessment;

[0104] Circulating tumor DNA and exosomes were collected from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden;

[0105] By combining single-cell sequencing technology, the distribution, activity and action pathway of meta-CBL in the tumor microenvironment were analyzed, and a high-resolution immune response map was obtained.

[0106] S104, intelligent feedback and optimization;

[0107] The collected data is uploaded to the AI ​​analysis platform, and machine learning models are used to conduct multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerance, and the extent of prognostic improvement.

[0108] Based on AI feedback, the dosage and delivery strategy of meta-CBL are optimized to customize personalized treatment plans for patients.

[0109] Preparation and loading of meta-CBL provided in this embodiment of the invention:

[0110] Cell sorting system:

[0111] B cells were isolated from the patient's peripheral blood and high-purity B cells were obtained using flow cytometry.

[0112] After sorting, B cells are stored in a sterile environment to ensure cell viability and purity for subsequent operations.

[0113] Gene transfection instrument:

[0114] Tumor antigen-specific receptor gene fragments are introduced into B cells using electroporation or viral vectors.

[0115] At the same time, gene editing technology can be used to give B cells the ability to secrete specific immunomodulatory factors, such as IFN-γ and IL-12.

[0116] In vitro culture device:

[0117] The transfected B cells were transferred to a dynamic culture device to provide suitable growth conditions;

[0118] Adding growth factors and supplementing nutrients promotes the expansion and functional differentiation of meta-CBLs;

[0119] The amplified meta-CBL was aliquoted using a cryopreservation device and prepared for treatment.

[0120] Immune remodeling of the tumor microenvironment provided in this embodiment of the invention:

[0121] Local drug delivery system:

[0122] meta-CBL is encapsulated via nanocarriers or liposome delivery systems to protect cells from attack by the body's immune system;

[0123] Using microinfusion pumps or hepatic artery perfusion technology, meta-CBL can be precisely delivered to the tumor site, ensuring efficient delivery to liver metastases.

[0124] Microenvironment monitoring sensors:

[0125] Microsensors are implanted at the tumor site to monitor the concentration of immune factors and metabolic indicators in the tumor microenvironment in real time.

[0126] The sensor transmits the monitoring results to the central processing unit in real time via wireless data transmission to determine the activity of meta-CBL in the tumor microenvironment;

[0127] Immune microenvironment remodeling:

[0128] meta-CBL activates the anti-tumor activity of CD8+ T cells and natural killer cells by secreting pro-inflammatory cytokines;

[0129] Meanwhile, the factors released by meta-CBL inhibit immunosuppressive cells and enhance the overall anti-tumor immune response.

[0130] like Figure 2 As shown, the real-time prognostic assessment provided by the embodiments of the present invention:

[0131] S201, Circulating Tumor DNA Detection:

[0132] ctDNA is isolated from the patient's blood using liquid biopsy technology;

[0133] The abundance of specific mutation sites in ctDNA can be detected using fluorescent PCR or digital PCR techniques to assess changes in tumor burden.

[0134] S202, Single-cell sequencing:

[0135] Meta-CBL and tumor cell samples were extracted from tumor tissue or blood and single-cell sequencing was performed.

[0136] The distribution, activity, and interactions of meta-CBL with other cells in the tumor microenvironment were analyzed.

[0137] Generate dynamic maps of the tumor immune microenvironment for precise evaluation of treatment efficacy;

[0138] S203, Results Integration and Dynamic Feedback:

[0139] The test data is uploaded to the cloud via a data interface, and combined with the patient's historical data, the treatment efficiency of meta-CBL is dynamically evaluated;

[0140] Adjust the dosage or delivery strategy of meta-CBL based on the results.

[0141] The intelligent feedback and optimization provided in this embodiment of the invention:

[0142] Data acquisition terminal:

[0143] Data is collected in real time from microenvironment sensors, liquid biopsy platforms, and single-cell sequencing equipment;

[0144] The data included immune factor concentrations, changes in tumor burden, and the distribution and activity of meta-CBLs.

[0145] AI analytics platform:

[0146] Utilize deep learning models to analyze and model the collected data;

[0147] Generate multidimensional analysis results, including dynamic changes in tumor burden, meta-CBL activity heatmap, and immune response curve;

[0148] Predict the short-term and long-term effects of treatment and identify potential risk factors;

[0149] Cloud storage and feedback system.

[0150] The cloud storage and feedback system provided in this embodiment of the invention:

[0151] All data is uploaded to a cloud platform for comparative analysis with a global gene database to search for new tumor markers and immune response mechanisms;

[0152] Based on the analysis results, the system provides clinicians with treatment optimization suggestions, including dose adjustment, meta-CBL reloading, or combination with other immunotherapy regimens.

[0153] like Figure 3 As shown, an embodiment of the present invention provides an application system for tumor-killing B cells in colorectal cancer liver metastases, comprising:

[0154] The preparation and loading module is used to extract B cells from the patient's peripheral blood, modify the B cells using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines, amplify meta-CBL in an in vitro culture system, and load it into a targeted delivery system through a specific delivery vector;

[0155] The tumor microenvironment regulation module is used to deliver the loaded meta-CBL to the tumor site via local injection or hepatic artery perfusion, and performs the following functions: secreting pro-inflammatory factors, activating the anti-tumor activity of CD8+ T cells and natural killer cells; neutralizing immunosuppressive factors in the tumor microenvironment; and synergistically acting with tumor antigen-specific cytokines to promote the direct killing of tumor cells.

[0156] The prognostic assessment module is used to collect circulating tumor DNA and exosomes from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden; combined with single-cell sequencing technology, it analyzes the distribution, activity, and pathway of meta-CBL in the tumor microenvironment and obtains high-resolution immune response maps.

[0157] The intelligent analysis and feedback module is used to upload the collected data to the AI ​​analysis platform and use machine learning models to perform multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerability, and the extent of prognostic improvement. Based on AI feedback, the meta-CBL dosage and delivery strategy are optimized to customize personalized treatment plans for patients.

[0158] Another object of the present invention is to provide a computer device comprising a memory and a processor, the memory storing a computer program, which, when executed by the processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases.

[0159] Another object of the present invention is to provide a computer-readable storage medium storing a computer program, which, when executed by a processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases.

[0160] Another objective of this invention is to provide an information data processing terminal, which is used to realize the application system of tumor-killing effect B cells in colorectal cancer liver metastases.

[0161] Specific implementation of the present invention:

[0162] System Structure and Method Steps

[0163] System Structure

[0164] Tumor-killing effector B cells (meta-CBL) preparation and loading module

[0165] Core technologies: gene editing and in vitro differentiation technology.

[0166] Equipment components: cell sorting system, gene transfection instrument, in vitro culture device.

[0167] Tumor microenvironment regulation module

[0168] Core technology: Immune microenvironment remodeling based on meta-CBL.

[0169] Equipment components: local drug delivery system, microenvironment monitoring sensors.

[0170] Prognostic assessment module

[0171] Core technology: Liquid biopsy combined with single-cell sequencing technology.

[0172] Equipment components: circulating tumor DNA (ctDNA) detection platform, single-cell sequencing equipment.

[0173] Intelligent Analysis and Feedback Module

[0174] Core technology: AI-driven efficacy assessment and treatment strategy optimization.

[0175] Equipment components: data acquisition terminal, AI analysis platform, cloud storage and feedback system.

[0176] Tumor-killing effector B cells (meta-CBL) preparation and loading module

[0177] Working principle:

[0178] Cell sorting system:

[0179] B cells were isolated from the patient's peripheral blood and high-purity B cells were obtained using flow cytometry (based on surface markers such as CD19).

[0180] After sorting, B cells are stored in a sterile environment to ensure cell viability and purity for subsequent operations.

[0181] Gene transfection instrument:

[0182] Electroporation or viral vectors (such as lentiviruses or adeno-associated viruses) are used to introduce tumor antigen-specific receptor (such as CAR-B cell receptor) gene fragments into B cells.

[0183] At the same time, gene editing technology (CRISPR / Cas9) can be used to give B cells the ability to secrete specific immunomodulatory factors, such as IFN-γ and IL-12.

[0184] In vitro culture device:

[0185] The transfected B cells were transferred to a dynamic culture device and provided with suitable growth conditions (e.g., 37°C, 5% CO2 concentration).

[0186] Adding growth factors (such as IL-2) and supplementing nutrients can promote the expansion and functional differentiation of meta-CBLs.

[0187] The amplified meta-CBL was aliquoted using a cryopreservation device and prepared for treatment.

[0188] Tumor microenvironment regulation module

[0189] Working principle:

[0190] Local drug delivery system:

[0191] meta-CBLs are encapsulated via nanocarriers or liposome delivery systems to protect cells from attacks by the body's immune system.

[0192] Using microinfusion pumps or hepatic artery perfusion technology, meta-CBL can be precisely delivered to the tumor site, ensuring efficient delivery to liver metastases.

[0193] Microenvironment monitoring sensors:

[0194] Miniature sensors are implanted at the tumor site to monitor in real time the concentration of immune factors (such as TGF-β and IL-10) and metabolic indicators (such as lactate concentration) in the tumor microenvironment.

[0195] The sensor transmits the monitoring results to the central processing unit in real time via wireless data transmission to determine the activity of meta-CBL in the tumor microenvironment.

[0196] Immune microenvironment remodeling:

[0197] meta-CBL activates the anti-tumor activity of CD8+ T cells and natural killer cells (NK cells) by secreting pro-inflammatory cytokines (such as IFN-γ).

[0198] Meanwhile, the factors released by meta-CBL inhibit immunosuppressive cells (such as regulatory T cells and MDSCs) and enhance the overall anti-tumor immune response.

[0199] Prognostic assessment module

[0200] Working principle:

[0201] Circulating tumor DNA (ctDNA) detection platform:

[0202] ctDNA is isolated from the patient's blood using liquid biopsy technology.

[0203] The abundance of specific mutation sites in ctDNA can be detected using fluorescent PCR or digital PCR techniques to assess changes in tumor burden.

[0204] Single-cell sequencing equipment:

[0205] Meta-CBL and tumor cell samples were extracted from tumor tissue or blood and single-cell sequencing was performed.

[0206] The distribution, activity, and interactions of meta-CBL with other cells in the tumor microenvironment were analyzed.

[0207] Generate dynamic maps of the tumor immune microenvironment for precise evaluation of treatment efficacy.

[0208] Results integration and dynamic feedback:

[0209] The test data is uploaded to the cloud via a data interface, and combined with the patient's historical data, the treatment efficiency of meta-CBL is dynamically evaluated.

[0210] Adjust the dosage or delivery strategy of meta-CBL based on the results.

[0211] Intelligent Analysis and Feedback Module

[0212] Working principle:

[0213] Data acquisition terminal:

[0214] Data is collected in real time from microenvironment sensors, liquid biopsy platforms, and single-cell sequencing equipment.

[0215] The data included immune factor concentrations, changes in tumor burden, and the distribution and activity of meta-CBL.

[0216] AI analytics platform:

[0217] The collected data is analyzed and modeled using deep learning models.

[0218] Generates multidimensional analysis results, including dynamic changes in tumor burden, meta-CBL activity heatmap, and immune response curves.

[0219] Predict the short-term and long-term effects of treatment and identify potential risk factors.

[0220] Cloud storage and feedback system:

[0221] All data is uploaded to a cloud platform for comparative analysis with a global gene database to search for new tumor markers and immune response mechanisms.

[0222] Based on the analysis results, the system provides clinicians with treatment optimization suggestions, including dose adjustment, meta-CBL reloading, or combination with other immunotherapy regimens.

[0223] The working principle of each module achieves efficient collaboration through the combination of hardware and software. The meta-CBL preparation and loading module ensures the preparation of high-quality tumor-killing cells; the tumor microenvironment regulation module optimizes the local immune microenvironment; the prognostic assessment module enables real-time, dynamic monitoring of treatment effects; and the intelligent analysis and feedback module provides precise suggestions for personalized treatment. This system can significantly improve treatment outcomes while reducing treatment risks, propelling the treatment of colorectal cancer liver metastases into the era of precision immunotherapy.

[0224] Methods and Steps

[0225] Preparation and loading of meta-CBL

[0226] B cells are extracted from the patient's peripheral blood and modified using gene editing technology (CRISPR / Cas9) to express tumor antigen-specific receptors (such as CAR or TCR) and pro-inflammatory cytokines (such as IFN-γ).

[0227] Meta-CBLs are amplified in an in vitro culture system and loaded into a targeted delivery system via a specific delivery vector (such as liposomes or exosomes).

[0228] Immune remodeling of the tumor microenvironment

[0229] The loaded meta-CBL is delivered to the tumor site via local injection or hepatic artery perfusion to perform the following functions:

[0230] It secretes pro-inflammatory factors and activates the anti-tumor activity of CD8+ T cells and natural killer cells (NK cells).

[0231] Neutralize immunosuppressive factors (such as TGF-β and IL-10) in the tumor microenvironment.

[0232] It works synergistically with tumor antigen-specific cytokines to promote the direct killing of tumor cells.

[0233] Real-time prognostic assessment

[0234] Circulating tumor DNA (ctDNA) and exosomes in the peripheral blood of patients were collected using liquid biopsy technology to dynamically monitor tumor burden.

[0235] By combining single-cell sequencing technology, we can analyze the distribution, activity, and pathway of meta-CBL in the tumor microenvironment and obtain a high-resolution immune response map.

[0236] Intelligent feedback and optimization

[0237] The collected data is uploaded to an AI analysis platform, and machine learning models are used to conduct multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerance, and the extent of prognostic improvement.

[0238] Based on AI feedback, the dosage and delivery strategy of meta-CBL are optimized to customize personalized treatment plans for patients.

[0239] Example 1: Local immunotherapy for colorectal cancer liver metastases based on meta-CBL

[0240] background

[0241] The patient was a 50-year-old male diagnosed with colorectal cancer with liver metastasis. He had poor tolerance to conventional chemotherapy. The liver metastasis was 3cm × 4cm in size. His liver function was relatively normal, but he was also in an immunosuppressive state (significantly elevated TGF-β).

[0242] Implementation steps

[0243] Sample collection and meta-CBL preparation:

[0244] 50 mL of blood was collected from the patient's peripheral blood, and B cells were separated and purified using a flow cytometry system.

[0245] The anti-tumor antigen-specific receptor gene and the immunomodulatory factor gene were introduced using a gene transfection instrument.

[0246] Meta-CBL was amplified in an in vitro culture device, ultimately yielding 2×10⁻⁶ cells / years. 6 Functional meta-CBL cells were preserved in a sterile cryopreservation system.

[0247] Local delivery and microenvironment regulation:

[0248] Under the guidance of DSA (digital subtraction angiography), a microinfusion pump is used to precisely deliver meta-CBL to the metastatic lesion area through the hepatic artery.

[0249] Simultaneously, a low-dose nano-sized TGF-β inhibitor is injected, along with a microenvironment regulation module, to reduce local immunosuppression.

[0250] Treatment monitoring and evaluation:

[0251] The circulating tumor DNA level was monitored every two weeks using a ctDNA detection platform to observe changes in tumor burden.

[0252] Single-cell sequencing technology was used to analyze the activity of meta-CBL in metastatic lesions and its interaction with tumor cells.

[0253] A follow-up CT scan one month after treatment showed that the tumor volume had decreased by 50% and the ctDNA level had decreased significantly.

[0254] Optimization feedback:

[0255] After the data was uploaded to the AI ​​analysis platform, it was recommended that the dose of the second meta-CBL injection be increased by 20% and the drug delivery time be extended.

[0256] Example 2: Postoperative prognostic assessment of colorectal cancer using meta-CBL combined with intelligent analysis platform

[0257] A 45-year-old female patient underwent resection of liver metastases from colorectal cancer. Preoperative immune assessment showed low CD8+ T cell activity in the tumor microenvironment, and the postoperative prognosis was unclear.

[0258] Postoperative preparation and injection of meta-CBL:

[0259] One week after surgical resection, peripheral blood samples were collected from the patient, and meta-CBL was prepared using gene editing technology.

[0260] The expanded meta-CBL was injected around the liver resection area to activate a local immune response.

[0261] Dynamic monitoring:

[0262] The tumor microenvironment immune factor data, including IFN-γ and IL-10 concentrations, are continuously collected using microenvironment monitoring sensors.

[0263] The distribution of meta-CBL and local immune response were monitored using multispectral imaging.

[0264] Prognostic assessment: One month after surgery, the concentration of circulating tumor DNA was monitored using a ctDNA detection platform, and changes in the liver microenvironment after surgery were analyzed using single-cell sequencing technology.

[0265] The AI ​​analysis platform models the collected immune response data to predict the risk of relapse in patients.

[0266] Treatment optimization: Based on the AI ​​platform's recommendations, the patient started adjuvant immunotherapy (second injection of meta-CBL) in the second month after surgery, combined with a low-dose PD-1 inhibitor.

[0267] Subsequent monitoring showed a 60% reduction in the risk of tumor recurrence, with no significant side effects observed in the patient.

[0268] Example 1 demonstrates the therapeutic potential of precise delivery of meta-CBL combined with microenvironment modulation, resulting in a significant reduction in tumor burden.

[0269] Example 2 emphasizes the role of meta-CBL in postoperative prognostic assessment, demonstrating how an intelligent analysis platform can optimize treatment plans and reduce the risk of recurrence. Both cases validate the effectiveness and feasibility of meta-CBL, providing a novel approach for the treatment and prognostic assessment of colorectal cancer liver metastases.

[0270] The meta-CBL combined intelligent analysis platform of this invention is mainly applied in the fields of tumor immunotherapy and prognostic assessment, particularly for precision treatment and dynamic monitoring after colorectal cancer liver metastasis surgery. Specific application areas include:

[0271] 1) Postoperative immunotherapy: Through the preparation and local injection of meta-CBL, the immune response activity in the tumor microenvironment is enhanced, which can be used as adjuvant therapy for high-risk patients after surgery.

[0272] 2) Tumor microenvironment regulation: Real-time collection of immune factor data, such as IFN-γ and IL-10 concentrations, using microenvironment monitoring sensors to dynamically assess immune changes at the tumor site.

[0273] 3) Postoperative prognostic assessment: By using the ctDNA detection platform and single-cell sequencing technology, we analyze the changes in the postoperative microenvironment and the concentration of circulating tumor DNA to provide data support for predicting the risk of recurrence.

[0274] 4) AI-powered intelligent treatment optimization: Relying on an AI analysis platform, immune factors and tumor dynamic data are modeled to generate personalized treatment plans and optimize medication strategies.

[0275] 5) Commercialization of the comprehensive treatment platform: The technical modules of this invention (such as the meta-CBL preparation system, microenvironment monitoring sensor, and AI analysis platform) can be applied as independent products in the treatment of other cancers.

[0276] In Example 1, the precise delivery of meta-CBL successfully activated the immune response around the hepatectomy area postoperatively. Dynamic monitoring data showed a significant increase in local IFN-γ concentration and a decrease in the immunosuppressive factor IL-10, demonstrating the regulatory role of meta-CBL in the local immune microenvironment. The patient's tumor burden was significantly reduced postoperatively, providing a new approach for adjuvant therapy after colorectal cancer liver metastasis surgery.

[0277] In Example 2, the AI ​​analysis platform, after modeling and using ctDNA detection and single-cell sequencing, significantly reduced the predicted risk of recurrence by 60%. This result was validated by subsequent imaging examinations and blood biomarker detection, confirming the accuracy and clinical value of the intelligent analysis platform in postoperative prognostic assessment.

[0278] The AI ​​platform provided treatment recommendations based on postoperative data, assisting the patient in receiving a second injection of meta-CBL in the second month post-surgery, combined with low-dose PD-1 inhibitor therapy. The patient experienced no significant side effects, and immune monitoring results showed a further enhanced immune response, validating the crucial role of the AI ​​platform in optimizing the treatment plan.

[0279] In both cases, the preparation and delivery of meta-CBL were performed efficiently, safely, and under control. The combination of microenvironment monitoring sensors and multispectral imaging technology further enhanced the accuracy of efficacy assessment. No immune-related adverse reactions occurred in any of the patients post-operatively, demonstrating the good safety and operability of the technology of this invention.

[0280] In summary, this invention, through two case studies, validates the remarkable efficacy of meta-CBL and the intelligent analysis platform in the treatment and prognostic assessment of colorectal cancer liver metastases, providing important technical support for the field of precision medicine.

[0281] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, and improvements made by those skilled in the art within the scope of the technology disclosed in the present invention, and within the spirit and principles of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for applying tumor-killing B cells in colorectal cancer liver metastases, characterized in that, Includes the following steps: Step 1, preparation and loading of meta-CBL; B cells were extracted from the patient's peripheral blood and modified using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines. Meta-CBL was amplified in an in vitro culture system and loaded into a targeted delivery system via a specific delivery vector. Step 2, Immune remodeling of the tumor microenvironment; The loaded meta-CBL is delivered to the tumor site via local injection or hepatic artery perfusion to perform the following functions: It secretes pro-inflammatory factors and activates the anti-tumor activity of CD8+ T cells and natural killer cells; Neutralize immunosuppressive factors in the tumor microenvironment; It works synergistically with tumor antigen-specific cytokines to promote the direct killing of tumor cells; Step 3, real-time prognostic assessment; Circulating tumor DNA and exosomes were collected from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden; By combining single-cell sequencing technology, the distribution, activity and action pathway of meta-CBL in the tumor microenvironment were analyzed, and a high-resolution immune response map was obtained. Step 4, Intelligent Feedback and Optimization; The collected data is uploaded to the AI ​​analysis platform, and machine learning models are used to conduct multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerance, and the extent of prognostic improvement. Based on AI feedback, the dosage and delivery strategy of meta-CBL are optimized to customize personalized treatment plans for patients.

2. The method for applying tumor-killing B cells in colorectal cancer liver metastases as described in claim 1, characterized in that, Preparation and loading of the meta-CBL: Cell sorting system: B cells were isolated from the patient's peripheral blood and high-purity B cells were obtained using flow cytometry. After sorting, B cells are stored in a sterile environment to ensure cell viability and purity for subsequent operations. Gene transfection instrument: Tumor antigen-specific receptor gene fragments are introduced into B cells using electroporation or viral vectors. At the same time, gene editing technology can be used to give B cells the ability to secrete specific immunomodulatory factors, such as IFN-γ and IL-12. In vitro culture device: The transfected B cells were transferred to a dynamic culture device to provide suitable growth conditions; Adding growth factors and supplementing nutrients promotes the expansion and functional differentiation of meta-CBLs; The amplified meta-CBL was aliquoted using a cryopreservation device and prepared for treatment.

3. The method for applying tumor-killing B cells in colorectal cancer liver metastases as described in claim 1, characterized in that, Immune remodeling of the tumor microenvironment: Local drug delivery system: meta-CBL is encapsulated via nanocarriers or liposome delivery systems to protect cells from attack by the body's immune system; Using microinfusion pumps or hepatic artery perfusion technology, meta-CBL can be precisely delivered to the tumor site, ensuring efficient delivery to liver metastases. Microenvironment monitoring sensors: Microsensors are implanted at the tumor site to monitor the concentration of immune factors and metabolic indicators in the tumor microenvironment in real time. The sensor transmits the monitoring results to the central processing unit in real time via wireless data transmission to determine the activity of meta-CBL in the tumor microenvironment; Immune microenvironment remodeling: meta-CBL activates the anti-tumor activity of CD8+ T cells and natural killer cells by secreting pro-inflammatory cytokines; Meanwhile, the factors released by meta-CBL inhibit immunosuppressive cells and enhance the overall anti-tumor immune response.

4. The method for applying tumor-killing B cells in colorectal cancer liver metastases as described in claim 1, characterized in that, The real-time prognostic assessment: Circulating tumor DNA detection platform: ctDNA is isolated from the patient's blood using liquid biopsy technology; The abundance of specific mutation sites in ctDNA can be detected using fluorescent PCR or digital PCR techniques to assess changes in tumor burden. Single-cell sequencing equipment: Meta-CBL and tumor cell samples were extracted from tumor tissue or blood and single-cell sequencing was performed. The distribution, activity, and interactions of meta-CBL with other cells in the tumor microenvironment were analyzed. Generate dynamic maps of the tumor immune microenvironment for precise evaluation of treatment efficacy; Results integration and dynamic feedback: The test data is uploaded to the cloud via a data interface, and combined with the patient's historical data, the treatment efficiency of meta-CBL is dynamically evaluated; Adjust the dosage or delivery strategy of meta-CBL based on the results.

5. The method for applying tumor-killing B cells in colorectal cancer liver metastases as described in claim 1, characterized in that, The aforementioned intelligent feedback and optimization: Data acquisition terminal: Data is collected in real time from microenvironment sensors, liquid biopsy platforms, and single-cell sequencing equipment; The data included immune factor concentrations, changes in tumor burden, and the distribution and activity of meta-CBLs. AI analytics platform: Utilize deep learning models to analyze and model the collected data; Generate multidimensional analysis results, including dynamic changes in tumor burden, meta-CBL activity heatmap, and immune response curve; Predict the short-term and long-term effects of treatment and identify potential risk factors; Cloud storage and feedback system.

6. The method for applying tumor-killing effector B cells in colorectal cancer liver metastases as described in claim 5, characterized in that, The cloud storage and feedback system: All data is uploaded to a cloud platform for comparative analysis with a global gene database to search for new tumor markers and immune response mechanisms; Based on the analysis results, the system provides clinicians with treatment optimization suggestions, including dose adjustment, meta-CBL reloading, or combination with other immunotherapy regimens.

7. A system for applying tumor-killing B cells in colorectal cancer liver metastases using the application method described in any one of claims 1-6, characterized in that, The system for applying tumor-killing B cells in colorectal cancer liver metastases includes: The preparation and loading module is used to extract B cells from the patient's peripheral blood, modify the B cells using gene editing technology to make them express tumor antigen-specific receptors and pro-inflammatory cytokines, amplify meta-CBL in an in vitro culture system, and load it into a targeted delivery system through a specific delivery vector; The tumor microenvironment regulation module is used to deliver the loaded meta-CBL to the tumor site via local injection or hepatic artery perfusion, and performs the following functions: secreting pro-inflammatory factors, activating the anti-tumor activity of CD8+ T cells and natural killer cells; neutralizing immunosuppressive factors in the tumor microenvironment; and synergistically acting with tumor antigen-specific cytokines to promote the direct killing of tumor cells. The prognostic assessment module is used to collect circulating tumor DNA and exosomes from the patient's peripheral blood using liquid biopsy technology to dynamically monitor tumor burden; combined with single-cell sequencing technology, it analyzes the distribution, activity, and pathway of meta-CBL in the tumor microenvironment and obtains high-resolution immune response maps. The intelligent analysis and feedback module is used to upload the collected data to the AI ​​analysis platform and use machine learning models to perform multidimensional analysis of the effects of meta-CBL, including tumor killing efficiency, patient tolerability, and the extent of prognostic improvement. Based on AI feedback, the meta-CBL dosage and delivery strategy are optimized to customize personalized treatment plans for patients.

8. A computer device, characterized in that, The computer device includes a memory and a processor. The memory stores a computer program, which, when executed by the processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases as described in any one of claims 1-6.

9. A computer-readable storage medium storing a computer program, which, when executed by a processor, causes the processor to perform the steps of the method for applying tumor-killing effector B cells in colorectal cancer liver metastases as described in any one of claims 1-6.

10. An information data processing terminal, characterized in that, The information data processing terminal is used to implement the application system of tumor-killing effect B cells in colorectal cancer liver metastasis as described in claim 7.

Images