Bispecific Dendritic Cell Engager for Tumor Immunity
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Solution Overview
Problem
Current cancer treatments struggle to effectively induce anti-tumor immunity by enhancing dendritic cell activation and maturation, particularly in engaging with immunogenic cell death (ICD) markers on tumor cells.
Innovation Solution
Development of anti-DC/anti-ICD bispecific engagers that target both dendritic cells and ICD markers on tumor cells, such as calreticulin and heat shock proteins, to enhance phagocytosis and activation of dendritic cells, thereby boosting anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional single-specific antibodies or treatments are used to target either dendritic cells or tumor cells, then the treatment mechanism is simple, but the ability to simultaneously enhance dendritic cell activation and engage ICD markers on tumor cells is insufficient
Solution Approach 1:
The bisspecific engager is divided into two distinct binding domains: a first binding domain that specifically binds to dendritic cells and a second binding domain that specifically binds to ICD markers on tumor cells. This segmentation allows each domain to be optimized for its specific target while maintaining overall functionality as a unified therapeutic agent.
Solution Approach 2:
The bisspecific engager performs multiple functions simultaneously: it engages dendritic cells to enhance activation and maturation, binds to ICD markers on tumor cells to promote phagocytosis, and bridges the gap between these two target populations. This multi-functionality resolves the contradiction by providing versatile anti-tumor activity through a single molecular construct.
2Productivity
If dendritic cells are activated and maturation is enhanced without simultaneous engagement of ICD markers, then immune response initiation is improved, but phagocytosis of ICD expressed tumor cells is not sufficiently enhanced
Solution Approach 1:
The patent merges the functions of dendritic cell activation and tumor cell engagement into a single bisspecific engager molecule. By combining a dendritic cell-targeting domain with an ICD marker-targeting domain, the invention ensures that both functions are performed simultaneously and reliably, eliminating the inconsistency that would arise from using separate agents.
3Stability of the object's composition
If bispecific engagers are designed with Fc fragments for enhanced stability, then pharmacokinetic properties are improved, but the complexity of molecular structure and manufacturing increases
Solution Approach 1:
The patent explores different molecular formats including full-length IgG bispecific antibodies and smaller recombinant bispecific formats derived from single chain variable fragment (scFv). By changing the structural parameters of the engager, the invention can optimize for either stability through Fc fragments or ease of manufacture through simplified scFv-based constructs, allowing flexibility in production approaches.
Data Source
AI summary
The present disclosure relates to treating cancer patients with anti-dendritic cells (anti-DCs)/anti-immunogenic cell death (anti-ICD) bispecific engager combined with tumor ICD inducers to enhance the dendritic cell activity. Exemplary polyvalent proteins include at least one DC binding site and at least one ICD binding site. In certain embodiments, the binding sites may be linked through a constant immunoglobulin region. Anti-DC and anti-ICD monoclonal antibodies are also provided.