CD19 CAR-T Leukemia Animal Model for Cytokine Release Syndrome
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Solution Overview
Problem
Current in vitro models fail to accurately simulate cytokine release syndrome (CRS) associated with CD19 chimeric antigen receptor (CAR)-T cell therapy for leukemia, limiting the development of effective intervention methods and posing safety concerns for patients.
Innovation Solution
An animal model of CD19 CAR-T cell therapy for leukemia complicated by CRS is developed, involving the preparation of a CD19 CAR-T cell line and construction of CRS animal models using SCID/Beige mice with varying tumor burdens and CD19 CAR-T cell infusions, allowing for the simulation of clinical CRS and investigation of therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If in vitro cell models are used to simulate CRS, then the model construction is simple, but the model cannot truly simulate the occurrence of CRS due to the complexity of cells and cytokines involved
Solution Approach 1:
The patent transitions from two-dimensional in vitro cell models to three-dimensional in vivo animal models (SCID/Beige mice) to simulate CRS. This dimensional change allows the model to accommodate the complexity of multiple cell types and cytokine interactions that cannot be adequately represented in simplified in vitro systems, thereby improving simulation accuracy while maintaining feasibility through the use of immunodeficient animals.
2Ease of operation
If clinical intervention methods using cytokine antagonists and glucocorticoids are used for CRS, then treatment can be provided, but serious adverse reactions cannot be avoided and efficacy is limited
Solution Approach 1:
The patent establishes an accurate animal model of CRS before testing interventions, enabling preliminary screening and optimization of treatment strategies. This preliminary modeling allows researchers to evaluate potential therapies in a controlled setting that truly mimics human CRS pathophysiology, reducing the risk of adverse reactions before clinical application and improving the likelihood of treatment efficacy.
Data Source
AI summary
Provide is an animal model of a chimeric antigen receptor (CAR)-T cell therapy for leukemia complicated by cytokine release syndrome (CRS), and a preparation method and use thereof. The preparation method of an animal model of a CD19 CAR-T cell therapy for leukemia complicated by CRS includes: preparing a CD19 CAR-T cell line: conducting cell separation of peripheral blood mononuclear cells (PBMCs), magnetic beads cell sorting of T cells, activation of the T cells, lentiviral infection, and amplification of CD19 CAR-T cells; and constructing CRS animal models after high-dose and low-dose CD19 CAR-T infusions: implanting a Nalm-6 cell line into a living animal to allow leukemia tumor burden to obtain a leukemia tumor-burdened living animal, and injecting the CD19 CAR-T cell line into the leukemia tumor-burdened living animal. The present disclosure further provides new use of the animal model of a CD19 CAR-T cell therapy for leukemia complicated by CRS.