Modulating Tregs and Bregs via APRIL-TACI Interaction
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Solution Overview
Problem
Current methods fail to selectively modulate the number and inhibitory immune activity of regulatory T cells (Tregs) and regulatory B cells (Bregs), which are crucial for immune regulation in tumor environments, due to shared genes and pathways with effector T cells, making it challenging to target them specifically for cancer treatment.
Innovation Solution
Targeting the APRIL/TACI interaction by administering agents that modulate the TACI receptor protein expressed by Tregs and Bregs, such as antibodies or RNA interfering agents, to selectively increase or decrease their number and inhibitory immune activity, thereby enhancing or suppressing their immune function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional immune modulation methods are used, then immune responses are affected, but Tregs and Bregs cannot be selectively modulated due to shared genes and pathways with effector T cells
Solution Approach 1:
The patent segments the immune cell population by identifying and targeting specific markers (TACI for Tregs and Bregs, CD19 for Bregs) that distinguish regulatory cells from effector T cells. This allows selective modulation of Tregs and Bregs through agents that bind to these specific markers, thereby resolving the contradiction between achieving selectivity and managing targeting complexity.
Solution Approach 2:
The patent applies local quality by using agents with specific binding properties targeting particular cell surface markers (TACI, CD19) on Tregs and Bregs. This localized targeting approach enables selective modulation of regulatory cells without affecting effector T cells, achieving precise control over which cell populations are modulated.
2Reliability
If Tregs are depleted to enhance anti-tumor immunity, then effector T cell function is improved, but immune homeostasis and self-tolerance may be compromised
Solution Approach 1:
The patent employs partial action by using anti-TACI antibodies or RNA interfering agents that selectively reduce Treg and Breg numbers and function without causing complete depletion. This partial modulation approach enhances anti-tumor immunity while maintaining sufficient regulatory cell populations to preserve immune homeostasis and prevent autoimmunity.
Solution Approach 2:
The patent changes the functional parameters of Tregs and Bregs by modulating their numbers, proliferation, and inhibitory activity through targeted agents. By adjusting these parameters rather than completely eliminating regulatory cells, the patent achieves enhanced anti-tumor responses while maintaining immune homeostasis.
3Reliability
If APRIL/TACI interaction is blocked to reduce Treg and Breg activity, then inhibitory immune function is decreased, but effects on other APRIL-receptor interactions may occur
Solution Approach 1:
The patent uses anti-TACI antibodies or RNA interfering agents as intermediaries to block the APRIL/TACI interaction specifically on Tregs and Bregs. These agents mediate the blockade of inhibitory signals without directly affecting other APRIL-receptor interactions on different cell types, thereby maintaining specificity while reducing Treg and Breg activity.
Data Source
AI summary
The present invention is based, in part, on methods for modulating regulatory T cells, regulatory B cells, and immune responses using modulators of the APRIL-TACI interaction.