Modified RELA Protein Engineering for T Cell Interferon Expression
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Solution Overview
Problem
Existing immune cell therapies, particularly those involving T cells, face limitations in functionality and survival in vivo, leading to suboptimal treatment outcomes for diseases such as cancer and infections, due to poor interferon production and susceptibility to immunosuppressive environments.
Innovation Solution
Engineering T cells with modified RELA proteins, specifically through substitution of lysine residues, to enhance interferon expression and metabolic capabilities, thereby improving survival, proliferation, and cytotoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cells are used in immune cell therapy, then anti-tumor and anti-infective responses are activated, but interferon production is insufficient leading to poor functionality and survival in vivo
Solution Approach 1:
The patent modifies the RELA protein (p65 subunit of NF-κB) by substituting lysine residues at specific positions (K122R, K123R, K310R, K314R, K315R) to change its functional parameters. This protein modification enables T cells to produce interferon constitutively and in response to stimulation, directly addressing the insufficient interferon production problem while improving reliability in vivo
Solution Approach 2:
The modified RELA protein enables T cells to autonomously produce interferon without requiring external stimulation or dependency on other cell types. This self-service capability allows T cells to maintain antiviral and antitumor functions independently, improving their survival and functionality in the complex in vivo environment
2Quantity of substance
If T cells are engineered with modified RELA protein, then interferon expression is enhanced, but device complexity increases
Solution Approach 1:
Instead of creating entirely new proteins or complex genetic constructs, the invention modifies existing RELA protein parameters through specific point mutations (lysine to arginine substitutions). This approach enhances interferon expression while maintaining the basic protein structure and function, thereby limiting the increase in device complexity
Solution Approach 2:
The invention targets specific lysine residues at defined positions (122, 123, 310, 314, 315) within the RELA protein sequence. By segmenting the modification approach into specific positional changes rather than global redesign, the complexity is managed and focused on critical functional regions only
Data Source
AI summary
The invention is in the field of immunotherapy. The present application provides modified RELA protein which are useful for inducing or promoting interferon expression by immune cells, in particular T cells. The invention enables the production of immune cells with an activated or enhanced interferon metabolism. The present application also relates to immune cells, in particular T cells, comprising and/or expressing a modified RELA protein according to the invention, such cells having an activated interferon metabolism. The present invention also provides in vitro and/or ex vivo method of preparing immune cells, in particular T cells, useful in immunotherapy. The invention also relates to methods for treating a patient, in particular a patient who has a cancer or an infectious disease, in particular an infection by a virus.