Porous Polymeric Device for Dendritic Cell Activation

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Solution Overview

Problem

Current cancer vaccination strategies face limitations due to the difficulty in effectively recruiting and activating dendritic cells, particularly CD8+ and plasmacytoid DC subsets, which are critical for anti-tumor immune responses, as traditional methods struggle to coordinate and sustain immune responses mediated by the heterogeneous DC network in cancer patients.

Innovation Solution

A device comprising a porous polymeric structure with embedded tumor antigens and Toll-like receptor (TLR) agonists, such as CpG-ODN and poly(I:C), is used to stimulate CD8+ and plasmacytoid dendritic cells in situ, leveraging the polymeric structure's ability to recruit, activate, and migrate immune cells, thereby enhancing anti-tumor immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional cancer vaccination strategies are used, then cancer treatment is attempted, but dendritic cell recruitment and activation is ineffective

Engineering Contradiction:
Improvedendritic cell activationVSAvoidimmune response generation
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent employs a porous polymeric scaffold structure that enables effective dendritic cell recruitment and activation. The porous architecture allows immune cells to infiltrate the device, contact embedded TLR agonists and tumor antigens, and receive coordinated stimulation that traditional vaccination methods cannot achieve.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent uses Toll-like receptor (TLR) agonists as intermediary molecules embedded in the polymeric device. These agonists mediate the interaction between the device and dendritic cells, triggering specific immune responses that traditional vaccines fail to elicit effectively.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If dendritic cells are used for therapeutic benefit, then anti-tumor immunity is enhanced, but cell isolation and processing becomes difficult

Engineering Contradiction:
Improveanti-tumor immune responseVSAvoiddendritic cell isolation
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent enables the device to perform self-service by automatically recruiting and activating dendritic cells at the tumor site without requiring external isolation and processing. The polymeric scaffold with embedded agonists and antigens creates an in situ environment where immune cells are drawn in and activated directly, eliminating the need for complex ex vivo manipulation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent incorporates tumor antigens and TLR agonists into the polymeric device beforehand, so that when dendritic cells are recruited to the site, they immediately encounter the pre-positioned stimulatory molecules. This preliminary preparation ensures effective activation without requiring time-consuming processing steps.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If heterogeneous dendritic cell subsets are targeted, then immune response specificity is improved, but coordination and sustainment becomes difficult

Engineering Contradiction:
Improveimmune response specificityVSAvoidimmune response coordination
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies local quality by embedding specific combinations of TLR agonists and tumor antigens within the polymeric scaffold to target particular dendritic cell subsets (CD8+ and plasmacytoid DCs) with localized precision. Different regions or components of the device can be designed to preferentially activate specific cell types, achieving subset-specific responses without requiring complex system-wide coordination.

Inventive Principle:
Principle #3Local quality

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

The approach significantly improves immune responses to cancer antigens, reduces tumor progression, and achieves long-term activation of immune cells, leading to enhanced anti-tumor immunity and prolonged immune response, as demonstrated by increased survival rates in animal models.

Implementation Method 1

the scaffold composition attracts a dendritic cell, introduces a immunogenic factor into the dendritic cell thereby activating the dendritic cell, and induces the dendritic cell to migrate away from the scaffold composition

Methodology Applied
Scientific EffectCell migration:

Implementation Method 2

presentation of Toll-like receptor (TLR) agonists in the context of the device is used for cancer vaccination. Incorporation and presentation of the TLR agonists embedded in structural polymeric devices specifically stimulates CD8(+) dendritic cells (DCs) and plasmacytoid DCs

Methodology Applied
Scientific EffectReceptor binding:

Data Source

PatentUS10568949B2Method of eliciting an anti-tumor immune response with controlled delivery of TLR agonists in porous polymerlc devices
Publication Date: 2020.02.25 DANA FARBER CANCER INSTITUTE INC
  • US10568949B2 patent drawing
  • US10568949B2 patent drawing
  • US10568949B2 patent drawing

AI summary

The present invention comprises compositions, methods, and devices for creating an stimulating an antigen-specific dendritic cell immune response. Devices and methods provide prophylactic and therapeutic immunity to subjects against cancer and infectious agents.