Nrf2 Activators Enhance NK and T Cell Survival in Cancer Therapy
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Solution Overview
Problem
Current adoptive cell therapies for cancer, such as those involving NK cells and T cells, face challenges in the tumor microenvironment due to oxidative stress, hypoxia, and immune suppression, leading to reduced efficacy and potential side effects from systemic administration of stimulatory molecules.
Innovation Solution
Contacting NK and T cells with Nrf2 activators like auranofin, sulforaphane, and dimethyl fumarate enhances their activity and survival under stress conditions, allowing them to better tolerate the tumor microenvironment and maintain therapeutic effectiveness while minimizing long-term immune stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If NK cells and T cells are transferred into the tumor microenvironment via adoptive cell therapy, then anti-tumor activity is improved, but the hostile tumor microenvironment with oxidative stress and immune suppression reduces cell viability and activity
Solution Approach 1:
The patent applies preliminary anti-action by pre-treating NK cells and T cells with Nrf2 activators before transferring them into the tumor microenvironment. This pre-treatment induces antioxidant defenses and stress resistance in the cells beforehand, enabling them to counteract the oxidative stress and immune suppression they will encounter in the tumor microenvironment, thereby maintaining their anti-tumor activity and viability
Solution Approach 2:
The patent uses Nrf2 activators as intermediary substances that mediate the protection of NK cells and T cells against tumor microenvironment stress. These activators induce the Nrf2 pathway, which upregulates antioxidant genes and protective proteins, creating an intermediary defense mechanism that shields the immune cells from direct damage by reactive oxygen species and other harmful factors in the tumor microenvironment
2Reliability
If stimulatory molecules are administered systemically to enhance immune cell activity, then cell activity is improved, but serious and sometimes fatal side effects occur
Solution Approach 1:
The patent applies local quality by concentrating the Nrf2 activator treatment on the specific target cells (NK cells and T cells) rather than administering stimulatory molecules systemically. This localized approach modifies only the relevant immune cells to enhance their stress resistance and activity, avoiding exposure of the entire organism to high doses of stimulatory molecules and thereby preventing serious systemic side effects
Solution Approach 2:
The patent enables self-service by activating the endogenous Nrf2 pathway within NK cells and T cells, allowing these cells to self-regulate their own stress responses and protective mechanisms. This eliminates the need for external administration of stimulatory molecules that cause systemic side effects, as the cells use their own intrinsic pathways to enhance their activity and survival
Data Source
AI summary
The present invention relates to uses of and methods of using activators of Nrf2 to enhance natural killer (NK) cell and/or T cell activity and/or survival, particularly in response to stress. The NK cells and/or T cells can be utilised in the treatment of cancer via enhanced cell therapy.