Anti-CD8α Antibodies for Transient 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 the VH and VL regions that efficiently deplete CD8α-expressing cells, followed by a controlled repopulation, including fusion proteins and nucleic acid molecules encoding these antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If anti-CD8α antibodies are used to deplete CD8+ cytotoxic T cells, then the ability to control and transiently deplete these cells is improved, but the risk of immune system dysfunction and inability to clear cancer cells or infected cells worsens
Solution Approach 1:
The antibody enables periodic depletion of CD8+ T cells rather than permanent elimination. The depletion is transient and reversible, allowing the immune system to recover and repopulate CD8+ T cells after the therapeutic effect is achieved, thus maintaining long-term immune functionality while providing controlled depletion during treatment
Solution Approach 2:
The invention changes the parameter of depletion duration from permanent to transient/controlled. By using anti-CD8α antibodies that induce temporary depletion rather than permanent elimination, the system allows dynamic control over CD8+ T cell levels, enabling clinicians to adjust depletion intensity and duration based on treatment response
2Object-generated harmful factors
If CD8+ cytotoxic T cells are depleted to treat diseases, then the therapeutic effect on autoimmune diseases and transplant rejection is improved, but the ability to clear cancer cells and infected cells worsens
Solution Approach 1:
The transient nature of the depletion allows for periodic treatment cycles where CD8+ T cells are temporarily reduced to control autoimmune activity, then allowed to repopulate to maintain anti-tumor and anti-infective immunity. This periodic approach enables the same cell population to serve different therapeutic functions at different times
Solution Approach 2:
The invention creates a dynamic treatment approach where CD8+ T cell levels are temporarily modulated rather than statically eliminated. The depletion is time-limited and reversible, allowing the immune system to adapt and maintain necessary functions while achieving therapeutic depletion when needed
3Duration of action of stationary object
If long-term depletion of CD8+ T cells is maintained to prevent disease recurrence, then the prevention of autoimmune disease recurrence is improved, but the risk of increased susceptibility to infections and tumors worsens
Solution Approach 1:
Instead of continuous long-term depletion, the invention employs periodic or transient depletion followed by repopulation phases. This allows the immune system to periodically reset and recover, maintaining disease prevention benefits while minimizing the risks associated with prolonged absence of CD8+ T cells
Solution Approach 2:
The transient depletion approach allows for monitoring of immune system response and disease control, enabling feedback-driven adjustment of treatment duration. If disease control is achieved, depletion can be stopped to allow immune recovery, preventing the accumulation of long-term risks while maintaining effective disease prevention
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.