Fibroblast Immunogenicity Reduction via Interferon-Gamma Treatment

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Solution Overview

Problem

Current cellular therapies for medical conditions face challenges due to immunogenicity issues, particularly with allogeneic cellular products that often trigger immune rejection, and the use of immunosuppressive drugs carries risks of infections, neoplasia, and organ failure.

Innovation Solution

The disclosure focuses on modifying fibroblasts to reduce their immunogenicity, allowing them to be used as 'universal donor' cells for therapeutic purposes. This is achieved through exposure to certain cells, such as immune cells, and agents like interferon gamma, which downregulate immunogenic molecules and inhibit alloreactive T cell responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If allogeneic cellular products are used for therapy, then therapeutic efficiency is improved, but immune rejection occurs

Engineering Contradiction:

Improvetherapeutic efficiencyVSAvoidimmune rejection

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-treating fibroblasts with interferon-gamma and other agents before transplantation to downregulate immunogenic molecules and reduce immunogenicity in advance, preventing immune rejection before it occurs

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent changes the immunological parameters of fibroblasts by treating them with interferon-gamma, which modifies cell surface molecule expression and reduces immunogenicity, allowing allogeneic cells to be used without severe immune rejection

Inventive Principle:

Principle #35Parameter changes

2Reliability

If immunosuppressive drugs are used to prevent rejection, then immune-mediated destruction is inhibited, but risk of infections and neoplasia increases

Engineering Contradiction:

Improveprevention of immune-mediated destructionVSAvoidinfections and neoplasia

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful immunogenicity of allogeneic fibroblasts into a benefit by using interferon-gamma treatment to selectively downregulate only the immunogenic molecules while preserving the therapeutic functions of the cells, eliminating the need for broad immunosuppression

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent extracts and removes specifically the immunogenic properties of fibroblasts through interferon-gamma treatment, separating the harmful immunogenic molecules from the beneficial therapeutic functions of the cells

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If calcineurin inhibitors are used for immune suppression, then rejection is prevented, but renal failure risk increases

Engineering Contradiction:

Improveprevention of rejectionVSAvoidrenal failure

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the problem of fibroblast immunogenicity into a solution by using interferon-gamma to selectively modify only the immunogenic molecules on fibroblast surfaces, eliminating rejection risk without requiring nephrotoxic calcineurin inhibitors

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250144151A1Interaction of fibroblasts and immune cells for activation and uses thereof

Publication Date: 2025.05.08 SPINALCYTE LLC

AI summary

The present disclosure is directed to systems, methods, and compositions for functional interaction of fibroblasts with one or more types of immune cells such that the interaction results in modification to the fibroblasts, the one or more types of immune cells, or both. In some embodiments, one or more certain agents are also utilized during the interaction or in lieu of one of the types of cells. In specific embodiments, cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.