VIP Nanoparticles Pulmonary Delivery GvHD Treatment

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Solution Overview

Problem

Graft-versus-host disease (GvHD) remains a major clinical challenge in the widespread clinical use of allogeneic hematopoietic stem cell transplantation, as donor T cells attack non-malignant epithelial tissues and organs, leading to high morbidity and mortality, and existing treatments are inadequate in preventing or effectively managing this condition.

Innovation Solution

Administration of vasoactive intestinal polypeptide (VIP) or its agonists, optionally conjugated to nanoparticles, in an aerosolized form for pulmonary delivery, which modulates systemic immune responses and attenuates T cell reactivity, thereby reducing the severity of GvHD and other inflammatory autoimmune diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If allogeneic hematopoietic stem cell transplantation is performed to treat hematological malignancies, then the graft versus host effect mediates donor T cells to expand and eliminate residual malignant cells, but donor T cells attack non-malignant epithelial tissues and organs causing graft-versus-host disease

Engineering Contradiction:

Improveefficacy of malignant cell eliminationVSAvoidgraft-versus-host disease

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

VIP acts as an intermediary substance that modulates the interaction between donor T cells and host tissues. The peptide binds to VIP receptors on T cells and other immune cells, mediating immunosuppressive effects that prevent harmful T cell attacks on non-malignant tissues while preserving anti-leukemia activity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physiological parameter of T cell activation and differentiation by introducing VIP or VIP agonists. These agents alter the balance between pro-inflammatory and anti-inflammatory cytokines, shift T cell polarization toward regulatory phenotypes, and modify the overall immune response parameters to reduce GvHD severity

Inventive Principle:

Principle #35Parameter changes

2Reliability

If VIP or VIP agonist is administered systemically to modulate immune responses, then T cell reactivity is attenuated and regulatory T cell frequencies increase, but the half-life of VIP in the alveolar space is limited reducing treatment efficacy

Engineering Contradiction:

Improveimmunosuppressive effectVSAvoidhalf-life of VIP in alveolar space

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The invention creates a composite therapeutic agent by conjugating VIP or VIP agonists to nanoparticles. This composite structure combines the immunomodulatory properties of VIP with the extended circulation and retention properties of nanoparticles, thereby prolonging the duration of action in the alveolar space while maintaining the desired immunosuppressive effects

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20240066101A1VIP and VIP Agonists, Nanoparticles, and Uses in Inflammatory T-Cell Mediated Disease

Publication Date: 2024.02.29 EMORY UNIVERSITY

AI summary

In certain embodiments, this disclosure relates to VIP and VIP agonists, optionally conjugated to nanoparticles, for use in methods of treating inflammatory T cell-mediated diseases or conditions, e.g., treating or preventing GvHD. In certain embodiments, this disclosure relates to methods of pulmonary administration of VIP and VIP agonists, optionally conjugated to nanoparticles. In certain embodiments, this disclosure contemplates nanoparticles disclosed herein.