Bispecific Construct Redirecting T Cells to IL-23R Target Cells
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Solution Overview
Problem
Current treatments for inflammatory and autoimmune diseases, as well as cancer, often rely on mechanisms that allow for redundant cytokine signaling, leading to incomplete efficacy and refractory patients, highlighting the need for more specific and stable bispecific molecules that can effectively target IL-23 receptor-expressing cells.
Innovation Solution
Development of a bispecific construct that specifically binds to cytotoxic effector T cells and IL-23 receptor-expressing target cells, such as Th17 cells, to induce cell killing and modulate the immune response, thereby treating inflammatory and autoimmune diseases and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for inflammatory and autoimmune diseases and cancer are used, then broad immune modulation is achieved, but specific targeting of IL-23 receptor-expressing cells is insufficient, leading to incomplete efficacy and refractory patients
Solution Approach 1:
The patent divides the immune system targeting into two distinct binding moieties: one targeting CD3 on T cells and another targeting IL-23R on pathogenic cells. This segmentation allows the bispecific construct to separately engage different cell types and pathways, achieving precise dual targeting that overcomes the limitations of single-target therapies while maintaining manageable molecular complexity
Solution Approach 2:
The bispecific construct serves multiple functions simultaneously: it acts as a bridge between cytotoxic T cells and IL-23R expressing target cells, provides dual specificity for both CD3 and IL-23R, and enables both direct target cell lysis and T cell-mediated cytotoxicity. This multi-functionality resolves the contradiction by integrating broad immune modulation with specific cell targeting in a single molecular entity
2Adaptability or versatility
If broad immune modulation is used to treat inflammatory diseases and cancer, then systemic immune activation occurs, but this leads to incomplete efficacy and refractory patients due to redundant cytokine signaling
Solution Approach 1:
The patent applies local quality by restricting immune activation to specific locations where both CD3+ T cells and IL-23R+ target cells are present. The bispecific construct only triggers immune responses at sites of disease pathology where both targets coexist, rather than causing widespread systemic activation. This localized approach maintains treatment versatility while minimizing harmful off-target effects
Solution Approach 2:
The bispecific construct acts as an intermediary molecule that bridges T cells and target cells only when both are present in proximity. This mediator function ensures that immune activation is contingent upon the physical presence of both cell types at the disease site, preventing uncontrolled systemic immune activation while maintaining the ability to modulate immunity where needed
3Ease of manufacture
If single-specific antibodies are used to target cytokines or receptors, then treatment is simpler, but redundant cytokine signaling pathways remain active, leading to refractory patients
Solution Approach 1:
The patent merges two specificities into a single bispecific construct: anti-CD3 and anti-IL-23R binding capabilities are combined in one molecular entity. This merging allows the treatment to simultaneously block IL-23 signaling and redirect T cells to target cells, eliminating redundant cytokine signaling pathways more completely than single-specific antibodies while maintaining a single administrable therapy that preserves treatment simplicity
Data Source
AI summary
The present invention relates to bispecific constructs that specifically bind to immune effector cells and, simultaneously, to IL23R-carrying target cells, as well as nucleic acids, vectors, host cells, pharmaceutical compositions, and methods of production and use thereof, including such bispecific constructs for use in treating inflammatory and/or autoimmune diseases and/or cancer.