Genetically Modified T Cells Expressing IL-2 or IL-15
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Solution Overview
Problem
Current T cell therapies for autoimmune and inflammatory diseases, as well as cancer, rely on exogenous IL-2 supplementation, which can be inadequate in patients with low IL-2 production, affecting Treg and Teff survival and function, and require repeated injections of large cell quantities.
Innovation Solution
Genetically modified Treg and Teff cells that stably express IL-2 or IL-15, using integrative viral vectors like lentiviruses or CRISPR-Cas9, to ensure constitutive or inducible expression, enhancing their survival and suppressive activity in IL-2-deprived environments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If exogenous IL-2 supplementation is used in T cell therapy, then Treg and Teff survival and function can be supported, but patients with low IL-2 production cannot benefit adequately
Solution Approach 1:
The patent modifies Tregs to autonomously produce IL-2 through genetic engineering, enabling them to self-support their survival and function without relying on exogenous IL-2 supplementation. This self-service capability ensures consistent therapeutic effect across all patient populations regardless of their endogenous IL-2 production levels.
Solution Approach 2:
The invention changes the functional parameter of Tregs by genetically modifying them to express IL-2, transforming them from IL-2 consumers to IL-2 producers. This parameter change enables the therapy to work effectively in patients with low IL-2 production by altering the fundamental cytokine dependency of the therapeutic cells.
2Reliability
If large quantities of Tregs are injected repeatedly, then therapeutic effect can be maintained, but treatment becomes cumbersome
Solution Approach 1:
By equipping Tregs with autonomous IL-2 production capability through genetic modification, the patent enables them to self-maintain their proliferation and survival in vivo. This self-service property allows a single injection of modified Tregs to provide sustained therapeutic effect without requiring repeated large-scale injections.
Solution Approach 2:
The patent performs preliminary genetic modification of Tregs ex vivo to establish autonomous IL-2 production before injection. This preliminary action ensures that the cells are pre-equipped with the necessary cytokine production capability, allowing them to immediately self-support upon injection and eliminating the need for subsequent booster injections.
3Productivity
If Tregs are cultured with large amounts of IL-2 ex vivo, then expansion can be achieved, but the cells face IL-2 deprivation upon re-injection into patients
Solution Approach 1:
The patent fundamentally changes the cytokine dependency parameter of Tregs by genetically modifying them to produce IL-2 autonomously. This parameter change allows the cells to be cultured with standard IL-2 levels ex vivo for expansion, while simultaneously ensuring they maintain survival capability after re-injection by having built-in IL-2 production capability.
Solution Approach 2:
The genetically modified Tregs are designed to self-produce IL-2, making them independent of exogenous IL-2 supplementation. This self-service capability ensures that regardless of the IL-2 conditions during ex vivo culture, the cells will maintain survival and function after re-injection into the IL-2-limited patient environment.
Data Source
Figure 1~2B
Figure 2C
Figure 2D~2E
AI summary
The invention relates to a composition comprising regulatory T (Treg) cells or effector T cells (Teff) which stably express an interleukin selected from the group consisting of interleukin-2 (IL-2) or interleukin-15 (IL-15).