Immunomodulatory Cloaking Cells for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Current immunotherapy approaches are unreliable and cumbersome, leading to non-specific antibody production and immune system suppression, which can cause autoimmune diseases and complicate treatments like organ transplants.
Innovation Solution
Genetically modified cells expressing specific transgenes and antigens to induce targeted immune tolerance, mitigating immune response activation and promoting antigen-specific immunity without widespread suppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive medication is used to dampen the immune system response, then transplant rejection and autoimmune disease are reduced, but side effects and risk of infection increase
Solution Approach 1:
The patent applies local quality by using antigen-specific tolerance inducing cells that target particular antigens (such as donor alloantigens or self-antigens) rather than suppressing the entire immune system. The cells express specific transgenes (PD-L1, HLA-G, Cd47, Cd200, FASLG, Ccl21, Mfge8, or Serpin B9) that locally modulate immune responses at the site of antigen presentation, providing targeted protection without systemic immunosuppression and its associated harmful effects.
2Reliability
If cell-based immunization is used to present antigen to the immune system, then antibody production can be induced, but the approach is unreliable and cumbersome and may lead to non-specific antibodies
Solution Approach 1:
The patent extracts and isolates specific immune modulatory functions from general cell-based immunization. By using defined transgenes (PD-L1, HLA-G, Cd47, Cd200, FASLG, Ccl21, Mfge8, or Serpin B9) in antigen-presenting cells, the invention extracts the specific mechanisms needed for tolerance induction, separating these functions from the complexity of whole-cell immunization and eliminating non-specific antibody production.
Solution Approach 2:
The patent changes the parameters of cell-based immunization by introducing specific transgenes that alter the immune modulatory properties of the cells. These transgenes change the expression profile of the cells to specifically induce tolerance to target antigens, transforming the unreliable and non-specific cell-based approach into a precise and controlled system.
3Reliability
If traditional vaccine development is used to produce immunity, then widespread immunity can be achieved, but the process is long and complex taking 10-15 years
Solution Approach 1:
The patent applies preliminary action by pre-modifying cells with specific transgenes before administration to the subject. The antigen-presenting cells are prepared in advance with the appropriate transgenes (PD-L1, HLA-G, Cd47, Cd200, FASLG, Ccl21, Mfge8, or Serpin B9) that will induce tolerance, eliminating the need for lengthy traditional vaccine development processes while still achieving reliable immunity.
Data Source
AI summary
Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.