IL-27 Producing B-1a Cells for Immune Suppression
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Solution Overview
Problem
Current treatments for uveitis, age-related macular degeneration (AMD), graft-versus-host disease (GVHD), and multiple sclerosis are limited by adverse effects and lack of effective long-term therapies, with no cure for AMD and inadequate management of progressive retinal degeneration.
Innovation Solution
An isolated population of mammal cells comprising 75% or higher B-1a regulatory cells expressing LAG-3, PD-1, CXCR4, and secreting IL-27, which are obtained by isolating CD5+ cells, activating them with BCR or TLR agonists, and exposing them to IL-27, then administered to suppress the immune system or used in transplants to prevent GVHD.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If steroids or immunosuppressants are used to treat uveitis, MS, or GVHD, then immune suppression is achieved, but serious adverse effects occur that preclude prolonged use
Solution Approach 1:
The patent uses IL-27 as an intermediary substance that mediates immune suppression through a different mechanism than traditional steroids. IL-27-producing B-1a cells act as living mediators that deliver suppressive signals to pathogenic T cells, achieving immune modulation without the harmful side effects of conventional immunosuppressants
Solution Approach 2:
The patent employs the body's own B-1a cells to produce IL-27 and perform immune suppression functions. By activating and expanding endogenous regulatory B cells, the therapy leverages the patient's own immune system for self-regulation, avoiding the need for external immunosuppressive drugs and their associated adverse effects
2Duration of action of moving object
If traditional immunosuppressive therapies are used for long-term treatment, then disease symptoms are managed, but the treatments lack sustainability due to adverse effects
Solution Approach 1:
The therapy activates the patient's own B-1a cells to continuously produce IL-27, creating a self-sustaining immune regulatory system. These endogenous cells can persist and function long-term without requiring continuous administration of external drugs, enabling sustainable long-term treatment
Solution Approach 2:
IL-27 serves as a sustainable intermediary that bridges the gap between B-1a cells and pathogenic T cells. The cytokine provides ongoing suppressive signals that can be maintained indefinitely, unlike finite courses of traditional immunosuppressants
3Reliability
If direct cytokine administration is used for immune suppression, then immune responses are suppressed, but the suppression is not sustained compared to cell-based therapy
Solution Approach 1:
Rather than administering cytokines transiently, the patent creates living factories (B-1a cells) that continuously produce IL-27 within the patient's body. These cells self-renew and persist long-term, providing sustained cytokine production and ongoing immune suppression without repeated injections
Solution Approach 2:
The patent uses B-1a cells as living carriers that deliver and continuously supply the IL-27 intermediary. This cell-based delivery system ensures prolonged presence and activity of the suppressive cytokine at the site of action, unlike direct cytokine administration which has limited half-life
Data Source
AI summary
The invention is directed to an isolated population of mammal cells comprising about 75% or higher B-1a regula e PBS-treated tory cells expressing the cell surface inhibitory receptors lympho-cyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1), and C-X-C chemokine receptor type 4 (CXCR4), and secreting interleukin-27 (IL-27). The invention is also directed to methods of preparing and using the cell population to suppress the immune system and/or to treat or prevent diseases.