TFR Cell Modulation via PD-1:PD-L1 Interaction Segmentation
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Solution Overview
Problem
Current methods for regulating immune responses are inadequate in controlling aberrant activation of immune responses, leading to autoimmune disorders and side effects from immunosuppressive therapies, and lack specificity in enhancing immunogenicity for desired antigens such as tumor antigens.
Innovation Solution
The discovery of PD-1:PD-L1 interactions regulating TFR cell differentiation and function, along with novel cell markers for identifying and separating TFH and TFR cells, allows for modulation of immune responses by altering PD-1 receptor interactions and enriching TFR or TFH cell populations for therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunosuppressive therapy is used to downregulate the immune system, then immune responses are suppressed, but subjects become susceptible to infections and cancers
Solution Approach 1:
The invention segments the immune system regulation by targeting specific T cell subsets (TFH and TFR cells) rather than applying generalized immunosuppression. This allows selective control of immune responses to specific antigens while preserving overall immune function against pathogens and tumors
Solution Approach 2:
The invention applies local quality by using antigen-specific T cell therapies that act locally on specific immune responses. TFR cells provide localized suppression to autoantigens or tumor antigens, while TFH cells provide localized enhancement to vaccine antigens, avoiding systemic immunosuppression
2Adaptability or versatility
If conventional T cell therapies are used, then immune responses are modulated, but specificity in targeting particular antigens is lacking
Solution Approach 1:
The invention segments T cell therapy into distinct functional subsets (TFH and TFR) with different roles. TFH cells are used for enhancing responses to specific antigens like vaccines, while TFR cells are used for suppressing responses to specific antigens like autoantigens or tumor antigens, providing antigen-specific precision
Solution Approach 2:
The invention uses antigen presentation as an intermediary mechanism to achieve specificity. T cells are activated or suppressed based on their interaction with antigen-presenting cells displaying specific antigens, allowing precise targeting of particular immune responses while sparing others
Data Source
AI summary
The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses, follicular helper T (TFH) cell-mediated immune responses or both, and the use of those methods in the treatment of diseases or conditions mediated by TFR or TFH cells. The invention also provides novel methods for identifying TFR and TFH cells in a population of cells. The invention also provides compositions comprising TFR cells that have enhanced suppressive activity as compared wild type TFR cells. The invention also provides compositions comprising T follicular regulatory (TFR) cells isolated from the peripheral blood of a subject wherein the composition is enriched for TFR cells. Methods of making and using the compositions of the invention to modulate an immune response are also provided.