Target-Primed Macrophages for S. aureus Immune Memory

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Solution Overview

Problem

Current approaches to addressing Staphylococcus aureus infections are hindered by recurring infections in healthy individuals, lack of effective conventional vaccines, and the emergence of antibiotic-resistant strains, necessitating novel methods to enhance innate or adaptive immunity.

Innovation Solution

The method involves priming macrophages with inactive target organisms or tumor cells to induce immune memory, which can then be administered to enhance antimicrobial and anticancer functions, either alone or in conjunction with traditional therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional vaccines targeting S. aureus are used, then immunity is attempted to be induced, but they lack efficacy and fail to provide protective immunity or immune memory

Engineering Contradiction:

Improveefficacy of vaccineVSAvoidprotective immunity induction

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-differentiating and priming macrophages ex vivo with heat-killed S. aureus before adoptive transfer. This pre-preparation of immune cells with target-specific memory enables them to mount an immediate and effective response upon transfer, overcoming the failure of conventional vaccines to induce protective immunity.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses heat-killed S. aureus as an intermediary to prime macrophages ex vivo. This inactivated form of the pathogen serves as a safe mediator that imparts antigen-specific memory to macrophages without causing infection, enabling the development of effective cellular immunotherapy.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If antibiotics are used to treat S. aureus infections, then bacterial growth is inhibited, but antibiotic-resistant strains emerge

Engineering Contradiction:

Improvebacterial growth inhibitionVSAvoidantibiotic resistance

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent converts the harmful effect of antibiotic overuse (selecting for resistant strains) into a beneficial approach by using heat-killed S. aureus to prime macrophages. This transforms the problem of pathogen exposure into a solution where inactivated pathogen material trains the immune system, providing protection without selecting for antibiotic resistance.

Inventive Principle:

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

Solution Approach 2:

The patent replaces the mechanical/chemical system of antibiotic treatment with a biological system of adoptive cellular immunotherapy. Instead of using antibiotics to kill bacteria, the treatment uses primed macrophages to provide immune-mediated protection, offering an alternative mechanism that does not contribute to antibiotic resistance.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If macrophages are primed ex vivo with heat-killed S. aureus, then antigen-specific immune memory is imparted, but the process requires complex ex vivo culture and adoptive transfer

Engineering Contradiction:

Improveimmune memory trainingVSAvoidex vivo culture process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses heat-killed S. aureus that serves multiple functions: it acts as a safe priming agent that cannot cause infection, provides comprehensive antigen exposure to train macrophage memory, and can be prepared in advance for scalable production. This multi-functional approach justifies the ex vivo complexity by enabling reliable immune memory training.

Inventive Principle:

Principle #6Universality (Multi-functionality)

4Reliability

If macrophages are adoptively transferred to provide immune protection, then protective immunity is enhanced, but the treatment requires personalized cell isolation and processing

Engineering Contradiction:

Improveprotective immunityVSAvoidcell isolation and processing

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by performing macrophage differentiation and priming ex vivo before adoptive transfer. This pre-preparation allows for quality control, optimization of immune memory training, and potential scalability through standardized protocols, making the personalized therapy more manufacturable.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS12116595B2Target-primed macrophages and therapeutic uses thereof

Publication Date: 2024.10.15 LOS ANGELES BIOMEDICAL RES INST AT HARBOR UCLA MEDICAL CENT

AI summary

Cell populations, compositions, and methods are provided relating to target priming of macrophage cells. The macrophages, once primed or activated with a microorganism, can be used to prevent or treat infection by the microorganism. Likewise, once primed or activated by a tumor cell or tumor antigen, the macrophage cell can be used to prevent or treat tumor of the same kind. The priming can be carried out in vitro or ex vivo. The macrophages can be isolated from the subject of disease prevention or treatment.