Bispecific Antigen-Binding Construct for Robo1-Targeted T Cell Activation
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Solution Overview
Problem
Current treatments for cancers with high Robo1 expression, such as liver and breast cancer, lack effective targeted therapies that can specifically activate immune cells to kill tumor cells.
Innovation Solution
A bispecific antigen binding construct comprising a single-chain variable fragment (ScFV) that binds to CD3 on immune cells and the Slit2D2 fragment binding to Robo1 on tumor cells, activating immune cells to target and kill cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then general treatment is provided, but they lack specific activation of immune cells to target tumor cells
Solution Approach 1:
The patent combines two functional domains into a single bispecific antigen-binding construct: the Slit2D2 domain that binds to Robo1 on tumor cells, and the anti-CD3 domain that binds to T cells. This merging allows the construct to simultaneously recognize tumor cells and activate immune cells, resolving the contradiction between targeted therapy effectiveness and immune cell activation capability
Solution Approach 2:
The bispecific antigen-binding construct performs multiple functions: it acts as a targeting moiety to recognize Robo1-expressing tumor cells, serves as an immune activation agent by binding CD3 on T cells, and functions as a bridge to recruit immune cells to the tumor site. This multi-functionality enables the construct to provide both targeted therapy and immune activation in a single molecule
2Reliability
If Robo1 is used as a tumor target, then high specificity for cancer cells is achieved, but lack of effective targeted therapy exists
Solution Approach 1:
The patent introduces the bispecific antigen-binding construct as an intermediary molecule that bridges the gap between Robo1 on tumor cells and the immune system. The construct's Slit2D2 domain binds to Robo1 with high specificity, while its anti-CD3 domain recruits T cells, effectively translating the target specificity into therapeutic action
Solution Approach 2:
The construct is segmented into distinct functional domains: the Slit2D2 domain for Robo1 binding and the anti-CD3 domain for immune cell recruitment. This segmentation allows each domain to perform its specific function optimally while working together as an integrated therapeutic agent
Data Source
AI summary
Disclosed are a bispecific antigen-binding construct and the preparation method and use thereof, wherein the construct comprises a first antigen binding unit and a second antigen binding unit, the first antigen binding unit is a single chain variable region antibody fragment ScFV which specifically binds to the surface antigen of immune cells, and the second antigen binding unit is a Slit2D2 protein fragment which specifically binds to the surface antigen Robo1 of tumour cells. That is to say, the construct can bind to the surface antigen of immune cells and the surface Robo1 molecule of tumour cells at the same time, so that as the distance between tumour cells and immune cells get smaller, the quiescent immune cells are effectively activated, and the effect of killing and wounding tumours is produced. The construct has advantages of small molecular weight and good tissue penetrability, has significant killing and wounding effects on the tumour cells which express a large amount of Robo1, and can be used in the development of anti-tumour drugs.