Cell-Based Adjuvants for Receptor-Independent Viral Uptake

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Solution Overview

Problem

Existing immune therapies using recombinant viral particles face challenges in achieving effective immune responses due to the lack of compatibility with conventional adjuvants and the dependency on viral uptake and expression, which can be unsuitable for neutralizing antigens.

Innovation Solution

The use of cell-based adjuvants, such as bacteria and yeast cells, to enhance viral uptake and expression of recombinant antigens in immune competent cells, particularly through the inclusion of pathogen-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP) proteins, toll-like receptor (TLR) ligands, and pattern recognition receptor (PRR) ligands, which activate antigen-presenting cells and increase gene transfer efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional adjuvants are used to stimulate immune reaction, then immune response is enhanced, but compatibility with recombinant viral particles is lost and antigenic interference occurs

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidcompatibility with recombinant viral particles

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces a cell-based adjuvant as an intermediary component that bridges the gap between recombinant viral particles and immune stimulation. The adjuvant cell expresses PAMPs and DAMPs that naturally stimulate immune cells without requiring conventional chemical adjuvants, thereby maintaining compatibility with the viral vector while achieving immune enhancement.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the fundamental parameter of adjuvant delivery from chemical/small-molecule form to a cellular form. This parameter change allows the adjuvant to be presented in a biologically compatible manner that does not interfere with viral entry or antigen expression, while still providing potent immune stimulation through cellular patterns recognition.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If IL-12 is used as a potentiating agent, then immune response is boosted, but immune response skewing and tolerance issues occur

Engineering Contradiction:

Improveimmune response potencyVSAvoidimmune response skewing and tolerance

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts the essential immune-stimulating functions (PAMP expression, cytokine production, antigen presentation) from the problematic IL-12 system and implements them through a natural adjuvant cell platform. This extraction allows selective stimulation of desired immune pathways while avoiding the harmful skewing effects associated with IL-12 overexpression.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the natural cellular recognition mechanisms (PAMPs, DAMPs) that normally detect pathogens into a controlled therapeutic tool. By expressing these patterns in an adjuvant cell, the system harnesses the body's natural immune recognition pathways to stimulate balanced immune responses without the harmful side effects of cytokine-based approaches.

Inventive Principle:

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

3Quantity of substance

If recombinant viral particles are used for antigen delivery, then gene transfer is achieved, but immune response against neutralizing antigens is insufficient

Engineering Contradiction:

Improveantigen delivery efficiencyVSAvoidneutralizing immune response

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent merges two separate functions into a unified system: the recombinant viral particle delivers the antigen gene, while the cell-based adjuvant provides immune stimulation. This merging creates a synergistic effect where the viral vector efficiently delivers genetic material and the adjuvant cell simultaneously stimulates robust immune responses against the expressed antigens.

Inventive Principle:

Principle #5Merging (Combining)

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

This approach significantly enhances viral uptake and expression of recombinant genes in cells lacking receptors, leading to improved immune responses and therapeutic outcomes, particularly in cancer therapy, without increasing degradation of the virus or expressed antigens.

Implementation Method 1

significantly enhances viral uptake and expression of recombinant genes in cells lacking receptors

Methodology Applied

Scientific EffectViral uptake: Absorption (physical)

Implementation Method 2

expression of recombinant genes in cells lacking receptors

Methodology Applied

Scientific EffectGene expression:

Data Source

PatentUS12350323B2Cellular adjuvants for viral infection

Publication Date: 2025.07.08 NANTBIOSCIENCE INC

AI summary

Two-component vaccine formulations and methods are contemplated where the vaccine has an adjuvant component and a therapeutic component. The therapeutic component comprises preferably a recombinant therapeutic virus encoding a therapeutic antigen while the adjuvant component comprises a non-host cell or immune stimulating portion thereof. Notably, use of the adjuvant component will result in significant uptake of the therapeutic component into immune competent cells, even in the absence of receptors for entry of the therapeutic component. In addition, such adjuvant also stimulates expression of the therapeutic antigen.