SARS-CoV-2-Specific T Cells With Steroid Resistance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments and preventive measures for coronavirus infections, such as SARS-CoV-2, lack effective solutions, particularly in managing severe atypical pneumonia associated with high morbidity and mortality, and there is a need for innovative approaches to enhance immune response and viral clearance.
Innovation Solution
The development of SARS-CoV-2-specific T cells, which are either autologous or allogeneic, are generated through ex vivo methods involving culturing peripheral blood mononuclear cells with peptides and cytokines, and may be genetically modified to express chimeric antigen receptors or have reduced expression of certain genes, to enhance their effectiveness and steroid resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments and preventive measures are used for coronavirus infections, then the current standard of care is maintained, but effective solutions for severe atypical pneumonia with high morbidity and mortality are lacking
Solution Approach 1:
The patent changes the parameter of immune response by introducing SARS-CoV-2-specific T cells with enhanced functionality. These T cells are generated through ex vivo expansion and genetic modification to express chimeric antigen receptors, fundamentally altering the immune response parameters to achieve better viral clearance and reduced mortality
Solution Approach 2:
The patent uses SARS-CoV-2-specific T cells as an intermediary between the host immune system and the virus. These engineered T cells act as mediators that directly target and eliminate infected cells, bridging the gap between conventional treatment and effective viral clearance
2Reliability
If SARS-CoV-2-specific T cells are generated through ex vivo culturing with peptides and cytokines, then targeted immune response is enhanced, but the complexity of cell preparation increases
Solution Approach 1:
The patent applies preliminary action by pre-expanding SARS-CoV-2-specific T cells ex vivo before administration. The T cells are cultured with SARS-CoV-2 peptides and cytokines in advance to generate large numbers of activated, virus-specific cells that can immediately upon infusion mount a potent anti-viral response
Solution Approach 2:
The patent uses cytokines (IL-2, IL-7, IL-15, IL-21) as intermediaries during the ex vivo expansion process. These cytokines mediate the activation and proliferation of T cells in response to peptide stimulation, enabling controlled generation of large numbers of specific immune cells
3Productivity
If T cells are genetically modified to express chimeric antigen receptors, then viral clearance capability is improved, but the difficulty of cell modification increases
Solution Approach 1:
The patent replaces the natural, slow T cell activation and differentiation process with a genetically engineered system. Chimeric antigen receptors are introduced that directly recognize SARS-CoV-2 antigens, substituting the complex natural immune recognition mechanism with a designed molecular system that provides faster and more specific viral clearance
Solution Approach 2:
The patent creates composite T cells that combine native T cell components with engineered chimeric antigen receptors. These hybrid cells integrate natural immune functions with artificial targeting capabilities, combining the best of both systems to achieve superior antiviral activity
4Stability of the object's composition
If T cells are modified to have reduced expression of certain genes for steroid resistance, then therapeutic stability is improved, but the complexity of genetic modification increases
Solution Approach 1:
The patent extracts or reduces the expression of specific genes that make T cells sensitive to glucocorticoids. By removing or downregulating these susceptibility genes, the engineered T cells become resistant to steroid-mediated depletion, allowing them to persist and function in patients receiving immunosuppressive therapy
Solution Approach 2:
The patent changes the genetic parameter of T cell composition by modifying gene expression levels. Specific genes are knocked down or eliminated to alter the T cells' responsiveness to glucocorticoids, fundamentally changing their survival characteristics in therapeutic settings
Data Source
AI summary
Embodiments of the disclosure includes methods of producing viral-specific therapy (VST) cells specific for the SARS-CoV-2 virus and uses of the cells. The methods may utilized peptide mixtures and stimulation of mononuclear cells using particular cytokine cocktails. The cells may also be genetically modified to lack expression of one or more endogenous genes, including one or more genes that renders the cells more effective and/or able to withstand deleterious conditions, such as the presence of glucocorticoids.