pH-Sensitive Adjuvant Carrier for CTL Induction

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Solution Overview

Problem

Current cancer immunotherapy combinations using different drugs with distinct mechanisms do not always enhance antitumor effects, necessitating a more effective approach to induce cytotoxic T cells (CTLs) for improved cancer treatment.

Innovation Solution

A combination of an adjuvant composition containing a pH-sensitive carrier and a natural immunity-activating substance, specifically an oligonucleotide with a CpG motif, used in conjunction with an immune checkpoint inhibitor such as an anti-PD-1 antibody, to enhance CTL induction and antitumor response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a combination of drugs with different immune system mechanisms is used, then immune therapy coverage is expanded, but antitumor effect enhancement is not always achieved

Engineering Contradiction:

Improveimmune therapy coverageVSAvoidantitumor effect enhancement

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines a pH-sensitive carrier system with a natural immunity-activating substance (CpG motif oligonucleotide) into a single adjuvant composition that delivers both components together to antigen-presenting cells, ensuring synergistic action for reliable antitumor effect enhancement while maintaining versatility through the checkpoint inhibitor combination

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The pH-sensitive carrier acts as an intermediary that facilitates the delivery of the CpG motif oligonucleotide to the cytosol of antigen-presenting cells, enabling cross-presentation of exogenous antigens on MHC class I molecules and ensuring consistent CTL induction that reliably enhances antitumor effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If exogenous antigen is delivered to cytosol for cross-presentation, then CTL induction is enabled, but delivery efficiency and consistency are challenging

Engineering Contradiction:

ImproveCTL induction capabilityVSAvoiddelivery efficiency

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The pH-sensitive carrier changes its physical state in response to pH variations - remaining intact at neutral pH for stable delivery but disassembling at acidic pH in the endosome to release the antigen into the cytosol, ensuring efficient and consistent cross-presentation for CTL induction

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The adjuvant composition is pre-formulated with the pH-sensitive carrier and CpG motif oligonucleotide in a specific ratio and structure before administration, ensuring that upon cellular uptake and acidification, the antigen is automatically released into the cytosol for efficient cross-presentation without requiring additional delivery steps

Inventive Principle:

Principle #10Preliminary action

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 combination significantly increases CTL induction and antitumor efficacy by facilitating antigen delivery to the cytosol and activating immune checkpoint inhibitors, leading to enhanced cancer treatment outcomes.

Implementation Method 1

a pH sensitive carrier capable of delivering an antigen to cytosol through the membrane disruptive function promoting effect

Methodology Applied

Scientific EffectpH-sensitive membrane disruption:

Implementation Method 2

an oligonucleotide having a CpG motif which is a Toll-like receptor agonist

Methodology Applied

Scientific EffectToll-like receptor activation:

Data Source

PatentUS11517620B2Adjuvant composition, and vaccine composition and drug kit each containing the same

Publication Date: 2022.12.06 TERUMO KK

AI summary

A combination of drugs having a higher antitumor effect is provided. There is provided an adjuvant composition containing a pH sensitive carrier and a natural immunity-activating substance, the adjuvant composition being used to be administered in combination with an immune checkpoint inhibitor.