AAV9-Mediated PDL1 Overexpression for Autoimmune Myocarditis Modeling
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Solution Overview
Problem
Current animal models for studying anti-PD-1/PD-L1 mAb-induced autoimmune myocarditis are inadequate, as they do not accurately simulate the human condition, leading to difficulties in understanding pathogenesis, identifying early warning markers, and developing effective treatments.
Innovation Solution
A method involving the use of AAV9 vectors to achieve high expression of PDL1 in myocardial tissue, combined with administration of anti-PD-1/PD-L1 mAb, to create a model that closely mimics the human condition of autoimmune myocarditis, allowing for dynamic monitoring of cardiomyopathy through cardiac magnetic resonance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-1/PD-L1 mAb is administered to treat malignant tumors, then anti-tumor effect is improved, but incidence of autoimmune myocarditis increases
Solution Approach 1:
The patent changes the parameter of PD-L1 expression level in myocardial tissue by using AAV9 vector for gene transfer. By creating a model with high PD-L1 expression (overexpressing group) compared to control levels, the patent enables the simulation of autoimmune myocarditis pathogenesis while maintaining the anti-tumor efficacy of anti-PD-1/PD-L1 mAb treatment.
Solution Approach 2:
The patent introduces AAV9 vector as an intermediary to deliver PD-L1 gene into myocardial tissue. This vector serves as a mediator that facilitates the expression of PD-L1 in cardiac cells, thereby creating the necessary conditions for anti-PD-1/PD-L1 mAb to induce autoimmune myocarditis in the animal model.
2Ease of manufacture
If animal model is established by directly administering anti-PD-1/PD-L1 mAb, then modeling process is simplified, but modeling success rate is low
Solution Approach 1:
The patent applies preliminary action by first using AAV9 vector to transfer and express PD-L1 gene in myocardial tissue before administering anti-PD-1/PD-L1 mAb. This pre-preparation of high PD-L1 expression environment significantly increases the modeling success rate, as the subsequent mAb administration can effectively trigger autoimmune myocarditis when PD-L1 is highly expressed.
Solution Approach 2:
The AAV9 vector acts as an intermediary that bridges the gap between simplified modeling process and high modeling success rate. It facilitates the expression of PD-L1 in cardiac tissue, creating the necessary conditions for anti-PD-1/PD-L1 mAb to induce autoimmune myocarditis, thereby achieving both process simplicity and high success rate.
3Adaptability or versatility
If existing animal models are used to study autoimmune myocarditis, then research on pathogenesis and treatment is enabled, but accuracy in simulating human condition is insufficient
Solution Approach 1:
The patent changes the key parameter of PD-L1 expression level in the animal model to match human disease characteristics. By creating a model with high PD-L1 expression in myocardial tissue, the patent achieves accurate simulation of human autoimmune myocarditis condition, enabling precise study of pathogenesis and treatment mechanisms.
Solution Approach 2:
The patent creates an animal model that copies the key feature of human autoimmune myocarditis - high PD-L1 expression in cardiac tissue. This copying of the critical disease parameter enables the model to accurately simulate human condition, thereby improving the accuracy of research findings.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The model achieves a high success rate in simulating the pathogenesis and clinical course of autoimmune myocarditis, enabling effective research on pathogenesis, early warning markers, and treatment development for anti-PD-1/PD-L1 mAb-induced myocarditis.
Implementation Method 1
mediating a model with AAV9 to achieve the high expression of PDL1 in a myocardial tissue
Implementation Method 2
applying an anti-PD-1/PD-L1 mAb to the model with high PDL1 expression in the myocardial tissue for modeling
Implementation Method 3
the cardiomyopathy can be dynamically monitored through cardiac magnetic resonance
Data Source
AI summary
A preparation method of an anti-PD-1/PD-L1 monoclonal antibody (mAb)-induced autoimmune myocarditis model is provided, including: mediating a model with adeno-associated virus 9 (AAV9) to achieve the high expression of PDL1 in a myocardial tissue, and applying an anti-PD-1/PD-L1 mAb to the model with high PDL1 expression in the myocardial tissue for modeling. The present disclosure also provides use of an animal model prepared by the preparation method. The model prepared by the present disclosure truly simulates the pathogenesis and clinical course of autoimmune myocarditis in a patient administered with an anti-PD1/PD-L1 mAb, is close to a pathophysiological status of a clinical patient, has a high modeling rate, and can be dynamically monitored.