Twin Immune Cell Engager Segmented Assembly for Tumor Localization
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Solution Overview
Problem
Current immunooncology approaches for cancer treatment often fail to activate T cells selectively and restrict activity to the tumor microenvironment, lacking the ability to incorporate additional functional domains and ensure localized treatment.
Innovation Solution
The development of TWICE complexes, which are two-component antibody complexes that combine multiple functions, including targeted immune cell binding agents with specific domains that become activated in the tumor microenvironment, allowing for localized action and simultaneous activation of T cells and binding of tumor-associated antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If prior constructs are used to activate T cells in the tumor microenvironment, then T cell activation is achieved, but the ability to incorporate additional functional domains and ensure localized treatment is lost
Solution Approach 1:
The construct is divided into two separate components: Component 1 contains the T cell engaging domain (anti-CD3 antibody) and Component 2 contains the tumor antigen binding domain. These components are administered separately and only assemble into a functional complex within the tumor microenvironment, enabling both versatility and localized activity.
Solution Approach 2:
A tumor-specific assembly mechanism acts as an intermediary that brings Component 1 and Component 2 together only at the tumor site. This assembly mechanism ensures localized treatment while allowing the construct to incorporate multiple functional domains through the two-component design.
2Adaptability or versatility
If a single therapeutic approach is used, then simplicity is maintained, but the ability to encompass multiple functions (T cell activation, checkpoint inhibition, etc.) is lost
Solution Approach 1:
The two-component construct is designed to be universally applicable to multiple cancer types and can incorporate various functional domains. Component 1 can engage different immune cell types while Component 2 can target different tumor antigens, enabling a single platform to deliver multiple therapeutic functions.
Solution Approach 2:
By segmenting the therapeutic construct into separate administurable components that assemble at the target site, the system reduces the complexity of delivering multiple functions simultaneously. Each component can be optimized independently while the assembled complex provides multi-functional therapy.
3Ease of operation
If traditional antibody complexes are used, then ease of administration is maintained, but the ability to restrict activity to the tumor microenvironment is lost
Solution Approach 1:
The therapeutic agent is segmented into two separately administurable components that do not form an active complex until they reach the tumor microenvironment. This segmentation allows simple administration of individual components while ensuring localized activity through tumor-specific assembly.
Solution Approach 2:
The construct exhibits different properties in different locations: as separate components during circulation (low activity) and as an assembled complex within the tumor microenvironment (high activity). This local quality difference ensures tumor-specific therapeutic action while maintaining ease of administration.
Data Source
AI summary
A Twin Immune Cell Engager (TWICE) is a kit or composition for treating cancer comprising a first component and second component. Each component comprises a targeting moiety that binds a tumor antigen expressed by the cancer or an antigen expressed by a non-cancer cell in the tumor microenvironment. In some embodiments, the first and second components each comprise an immune cell binding domain capable of immune cell binding activity when binding the immune cell binding domain in the other component, and a complementary binding domain capable of binding to a complementary antigen when binding the complementary binding domain in the other component. In some embodiments, the first and/or second components comprise a complementary functional domain with activity when targeted to the cancer cell or its microenvironment.The present TWICE complexes offer a unique ability to combine multiple functions into a two-component complex that becomes activated in the tumor microenvironment. The present complexes, thus, provide meaningful advantages in having a single approach to administering a two-component complex that is localized to the tumor microenvironment and has the ability to effect two different signals to benefit patients. This unique construct offers benefits that were not present in prior art constructs.