Antigen-Specific T Cells for Targeted B-Cell Immune Tolerance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing therapies induce undesired immune responses, such as antibody production against therapeutic proteins or allergens, leading to conditions like transplant rejection, allergies, and asthma, and current immunosuppression methods are non-specific and can suppress beneficial immune responses.
Innovation Solution
Targeting antigen-specific B cells using engineered regulatory or cytotoxic T cells, or bispecific antibodies, to reduce undesirable immune responses by exposing B cells to T cells expressing the target antigen or a domain thereof, or using bi-specific antibodies to induce killing or suppression of antigen-specific B cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If non-specific regulatory T cells are used for immunosuppression, then immune responses to therapeutic agents are reduced, but desired immune responses to pathogenic infections and cancer are also suppressed
Solution Approach 1:
The patent segments the immune system response by creating antigen-specific regulatory T cells that target only B cells producing antibodies against specific therapeutic agents (e.g., FVIII). This segmentation allows suppression of harmful immune responses to particular therapies while preserving desired immune responses to pathogens and cancers through other immune mechanisms.
Solution Approach 2:
The invention applies local quality by engineering regulatory T cells with specific antigen recognition capabilities (e.g., anti-FVIII specificity) rather than using non-specific regulatory T cells. This localized specificity ensures that immunosuppression occurs only at the target antigen-B cell interface, leaving other immune functions intact.
2Productivity
If conventional FVIII therapies are administered frequently, then hemophilia A patients receive adequate clotting factor, but greater than 20% of patients develop undesired immune responses against therapeutic FVIII proteins
Solution Approach 1:
The patent applies preliminary action by administering antigen-specific regulatory T cells before or during FVIII therapy to prevent the development of inhibitory antibodies. This proactive approach establishes immune tolerance before the harmful immune response can develop, allowing continuous FVIII administration without inducing antibody production.
Solution Approach 2:
The invention converts the harmful immune response (antibody production against FVIII) into a beneficial outcome by using the same antigen specificity to generate regulatory T cells. These engineered T cells recognize FVIII and use this recognition to suppress B cells that would otherwise produce harmful antibodies, thereby protecting the therapeutic efficacy of FVIII.
3Object-affected harmful factors
If non-specific immunosuppression is applied, then undesirable immune responses are reduced, but the complexity of managing side effects increases
Solution Approach 1:
The patent changes the specificity parameter of regulatory T cells from non-specific to antigen-specific (e.g., FVIII-specific). This parameter change transforms the broad, difficult-to-manage immunosuppression into a targeted therapy that automatically limits its action to the intended target, reducing the complexity of managing side effects.
Data Source
AI summary
Described herein are agents and methods for targeting antigen-specific B cells using engineered T cells, such as regulatory T cells or cytotoxic T cells, or bi-specific antibodies. The agents and methods can be used to reduce undesirable immune responses.