Hematopoietic Stem Cell Therapy for COVID-19 Immune Reconstitution

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Solution Overview

Problem

Current treatments for severe COVID-19 lack effectiveness, with no proven therapeutics available, and there is an urgent need for safe and effective therapies to address the high morbidity and mortality rates caused by SARS-CoV-2 infections.

Innovation Solution

Administering hematopoietic stem cells, either alone or in combination with hematopoietic stem cell mobilizing agents and programmed death 1 (PD-1) antagonists, to treat COVID-19, which involves mobilizing stem cells, enriching them for specific cell types, and using PD-1 antagonists like nivolumab or other antibodies to enhance immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard of care treatment alone is used for severe COVID-19, then treatment simplicity is maintained, but treatment effectiveness is insufficient

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple therapeutic agents (hematopoietic stem cells, mobilizing agents, and PD-1 antagonists) into a single integrated treatment protocol. This merging of previously separate treatments into a coordinated regimen addresses the inadequacy of standard care alone while managing complexity through structured combination therapy

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The treatment uses a composite approach by combining different types of cellular and molecular therapies (stem cells, cytokines, and immunomodulators) to create a multi-component therapeutic system that targets multiple aspects of COVID-19 pathophysiology simultaneously, thereby improving overall treatment effectiveness

Inventive Principle:

Principle #40Composite materials

2Reliability

If hematopoietic stem cells are administered alone, then treatment protocol is simpler, but immune response enhancement is insufficient

Engineering Contradiction:

Improveimmune response enhancementVSAvoidtreatment protocol complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs preliminary action by first administering hematopoietic stem cell mobilizing agents to prepare and mobilize stem cells from bone marrow before administering the stem cells themselves and subsequent PD-1 antagonists. This sequential preparation enhances the effectiveness of subsequent treatments while structuring the protocol complexity in a manageable sequence

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The treatment uses hematopoietic stem cells as intermediary elements that mediate between the administered mobilizing agents and the final immune response enhancement achieved through PD-1 antagonists. These stem cells serve as a bridge, differentiating into various immune cells that amplify the overall therapeutic effect

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If PD-1 antagonists are added to stem cell therapy, then T cell immunity is enhanced, but treatment complexity increases

Engineering Contradiction:

Improvesystemic T cell immunityVSAvoidtherapy combination complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent implements periodic action through scheduled administration of PD-1 antagonists at specific time intervals following stem cell mobilization and infusion. This timing-based approach allows the immune system to progressively respond to each intervention, enhancing T cell immunity through repeated, strategically timed immunomodulatory events rather than continuous treatment

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The treatment protocol is designed to be dynamic, adjusting the timing and dosing of PD-1 antagonists based on the patient's immune response progression. This dynamic approach allows optimization of T cell enhancement while adapting treatment complexity to individual patient needs and response patterns

Inventive Principle:

Principle #15Dynamics

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

The approach leads to rapid expansion of peripheral T cells, enhancement of systemic T cell immunity, and adaptive immune reconstitution, potentially improving survival and reducing morbidity and mortality in severe COVID-19 cases.

Implementation Method 1

rapid expansion of peripheral T cells, enhancement of systemic T cell immunity, and adaptive immune reconstitution

Methodology Applied

Scientific EffectCell differentiation:

Implementation Method 2

administering to the subject a hematopoietic stem cell mobilizing agent in an amount effective to treat the disease

Methodology Applied

Scientific EffectStem cell mobilization:

Implementation Method 3

administering a programmed death 1 (PD-1) antagonist... an agent that binds to and antagonizes programmed death 1 (PD-1)

Methodology Applied

Scientific EffectReceptor antagonism:

Data Source

PatentUS20230183370A1Stem cell immunomodulatory therapy for covid-19 infection

Publication Date: 2023.06.15 UNIV OF FLORIDA RESEARCH FOUNDATION INC

AI summary

The disclosure provides methods of treating coronavirus infections (e.g., COVID-19) by administering hematopoietic stem cells, with or without an immune checkpoint inhibitor (e.g., PD-1 antagonist). The disclosure also provides methods of treating coronavirus infections (e.g., COVID-19) by adoptive cell transfer of polyclonal T cells and coronavirus-specific T cells (e.g., SARS-CoV-2-specific T cells).