Anti-CD8α Antibodies for Rapid T-Cell Depletion Control
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Solution Overview
Problem
There is a need for a therapeutic tool that can specifically target and transiently deplete CD8+ cytotoxic T cells in a controlled manner to address various diseases and disorders while allowing for a controlled repopulation of these cells.
Innovation Solution
Development of anti-CD8α antibodies with specific CDR sequences in their variable regions that bind to CD8α, enabling efficient depletion and subsequent controlled repopulation of CD8α-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional antibodies are used to deplete CD8+ T cells, then some depletion effect is achieved, but the depletion is not fast or complete enough
Solution Approach 1:
The patent modifies the antibody structure by optimizing the CDR regions (particularly VH-CDR3 and VL-CDR3) to achieve higher affinity binding to CD8α. This structural parameter change enables the antibody to rapidly bind and internalize CD8α, resulting in fast and complete depletion of CD8+ T cells within 24-48 hours, resolving the contradiction between depletion speed and completeness.
2Reliability
If CD8+ T cells are depleted to treat diseases, then therapeutic effect is achieved, but the ability to control repopulation is lost
Solution Approach 1:
The patent employs a dynamic depletion approach where the antibody treatment is administered in controlled cycles. The depleting antibody is given to achieve rapid CD8+ T cell depletion for therapeutic effect, followed by a cessation period that allows natural repopulation. This dynamic on-off treatment pattern provides controlled therapeutic action while preserving the ability to restore immune function, resolving the contradiction between therapeutic control and depletion duration.
Data Source
AI summary
Novel anti-CD8α (cluster of differentiation 8 alpha) antibodies and antigen-binding fragments thereof, a fusion protein including the anti-CD8α antibodies and antigen-binding fragments thereof, and a nucleic acid molecule encoding the anti-CD8α antibodies and antigen-binding fragments thereof. Also, pharmaceutical compositions including the anti-CD8α antibodies and antigen-binding fragments thereof. Further, methods using the anti-CD8α antibodies and antigen-binding fragments thereof for treating CD8-related diseases and in vitro methods in which CD8a-expressing cells are depleted in a sample or in which CD8α is detected or quantified in a sample.