Bispecific CD28 Molecule for Targeted T-Cell Costimulation
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Solution Overview
Problem
Existing immunotherapy agents targeting CD28, such as anti-CD28 antibodies, pose safety risks due to systemic overstimulation and non-specific activation of T-cells, limiting their effectiveness in treating conditions like cancer.
Innovation Solution
A multifunctional molecule covalently linked to both CD28 and another T-cell antigen, like PD-1, for targeted and controlled T-cell activation, avoiding systemic activation and non-specific effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If anti-CD28 antibodies are used for T-cell activation, then T-cell activation is enhanced, but systemic overstimulation and non-specific activation occur causing safety risks
Solution Approach 1:
The patent applies local quality by making the T-cell activation effect localized rather than systemic. The bispecific antibody structure enables targeted delivery to tumor-associated T-cells through dual binding to CD28 and tumor-specific antigens, concentrating the activating effect where needed while avoiding widespread systemic activation and its associated safety risks.
Solution Approach 2:
The bisspecific antibody acts as an intermediary molecule that mediates between the CD28 co-stimulatory pathway and tumor-specific antigens. This intermediary structure allows controlled, targeted T-cell activation by requiring simultaneous binding to both CD28 and tumor antigens, thereby preventing non-specific activation while maintaining therapeutic efficacy.
2Reliability
If bisspecific antibodies targeting both CD28 and tumor antigens are used, then direct tumor targeting with costimulatory effect is achieved, but complexity of the molecule increases
Solution Approach 1:
The patent merges two separate antibody functions into a single bispecific antibody molecule. By combining the CD28-binding domain with the tumor antigen-binding domain in one molecule, the invention achieves simultaneous tumor targeting and costimulatory activation, improving reliability while the merged structure actually reduces overall system complexity compared to using separate antibodies.
Solution Approach 2:
The bisspecific antibody exhibits multi-functionality by simultaneously performing tumor targeting and T-cell costimulation in a single molecule. This universal design allows the same molecule to execute multiple therapeutic functions, improving reliability through coordinated action while avoiding the need for separate administration of multiple agents.
Data Source
AI summary
The present invention provides a multifunctional molecule comprising an agonistic anti-CD28 binding domain covalently linked to another binding moiety that binds to a target specifically expressed on T cells surface, and uses thereof.