PS-Binding Biomolecules for Exhausted Memory T Cell Reactivation

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Solution Overview

Problem

The role of activation-induced phosphatidylserine (PS) exposure in T cell function, particularly in the context of infections or autoimmune diseases, remains poorly understood, and existing PS-targeting antibodies have limited efficacy due to weak neutralizing activity and potential side effects.

Innovation Solution

Delivering therapeutically effective amounts of PS-binding biomolecules, such as antibodies or annexins, to peripheral blood mononuclear cells (PBMCs) in the presence of specific antigens to restore effector function in exhausted or non-responsive memory T cells, and using these biomolecules to modulate immune checkpoints like TIM3 and TIGIT.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing PS-targeting antibodies are used to target phosphatidylserine on T cells, then some immune modulation effect is achieved, but the neutralizing activity is weak and side effects occur

Engineering Contradiction:

Improveefficacy of PS-targeting antibodiesVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the properties of PS-targeting molecules by engineering antibodies with enhanced affinity and specificity for phosphatidylserine. This involves changing parameters such as binding constant, specificity ratio, and molecular structure to achieve stronger neutralizing activity while reducing off-target effects and side effects.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses composite antibody structures that combine multiple functional domains - including high-affinity PS-binding regions and epitope-specific recognition regions - to create molecules that simultaneously achieve strong neutralizing activity against PS-expressing cells while maintaining specificity for antigen-responsive T cells, thereby reducing side effects.

Inventive Principle:

Principle #40Composite materials

2Reliability

If memory T cells are exhausted or non-responsive to antigens, then immune response to infections or cancers is suppressed, but restoring effector function requires targeted intervention

Engineering Contradiction:

Improveeffector function of memory T cellsVSAvoidcomplexity of restoration method

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs PS-binding antibodies as intermediary molecules that bridge the gap between exhausted memory T cells and their reactivation. These antibodies bind to PS on the surface of exhausted T cells, serving as a mediator that delivers reactivation signals and restores effector function without requiring complex multi-step protocols.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention develops a universal approach using PS-binding antibodies that can restore effector function in memory T cells across multiple disease contexts (infections, cancers, autoimmune conditions) without needing disease-specific customization, thereby simplifying the intervention complexity while maintaining broad applicability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Loss of information

If PS externalization occurs in live cells like T cells during activation, then immune regulation is modulated, but the role in T cell function remains poorly understood

Engineering Contradiction:

Improveunderstanding of PS role in T cell functionVSAvoidresearch progress

Core Design Contradiction:

Loss of informationVSProductivity

Solution Approach 1:

The patent utilizes the natural PS externalization phenomenon that occurs during T cell activation as a self-marking mechanism. By designing antibodies that specifically recognize and bind to this self-exposed PS on activated T cells, the system enables automatic identification and targeting of antigen-responsive memory T cells without requiring external labeling or complex detection methods, thereby advancing understanding of PS function.

Inventive Principle:

Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enhances antigen-specific memory T cell activation, increases effector function, and clears infections like TB in vitro, offering a targeted and effective treatment strategy for diseases like HIV-TB coinfection and autoimmune disorders.

Implementation Method 1

phosphatidylserine (PS)-binding biomolecules

Methodology Applied

Scientific EffectPhosphatidylserine binding: Absorption (physical)

Data Source

PatentUS20250289907A1Phosphatidylserine targeting molecule combined with memory t cell antigen for therapeutic, diagnostic and adjuvant use

Publication Date: 2025.09.18 RUTGERS THE STATE UNIV

AI summary

Phosphatidylserine (PS)-targeting biomolecules and related methods for impacting the function of memory T cells are provided. In the present methods, PS-binding biomolecules are delivered to peripheral blood mononuclear cells (PBMCs) or whole blood of a subject in the presence of antigens specific to one or more diseases, wherein the PBMCs or whole blood comprise memory T cells that are exhausted or non-responsive to the antigens specific to the one or more diseases. Delivery of the PS-binding biomolecules to the PBMCs or whole blood restores effector function in the antigen non-responsive memory T cells. The administration of PS-binding biomolecules to PBMCs or blood with T cell antigens specific to pathogens can also be used to develop ultrasensitive diagnostics for latent infections or memory T cells response induced by natural infection or vaccination.