Multi-Antigen CAR T Cell Engineering for Tumor Microenvironment Targeting

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Solution Overview

Problem

Current cancer immunotherapy using CAR T cells faces challenges in selectively targeting tumor microenvironment cells without affecting healthy cells, due to non-specific antigen expression and immunosuppressive barriers, requiring a fast and reliable method for patient-specific antigen selection.

Innovation Solution

A method involving cell samples from tumor and non-tumor microenvironment cells, using fluorescent conjugates to identify specific antigens on TME cells, such as alpha-SMA, CD74, CXCL12, and PDGFRbeta, to engineer CAR T cells that selectively target TME cells while sparing healthy cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single antigen target is used for CAR T cell therapy, then the treatment process is simplified, but the specificity and safety are compromised due to non-specific antigen expression on healthy cells

Engineering Contradiction:

ImproveCAR T cell therapy process simplicityVSAvoidTreatment safety and specificity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent divides the antigen recognition system into multiple segments by using CAR T cells that simultaneously target multiple antigens (e.g., CD10 and PDGFRβ). This segmentation ensures that healthy cells expressing only one antigen are not attacked, while tumor cells expressing multiple antigens are selectively eliminated, thereby resolving the contradiction between process simplicity and treatment safety.

Inventive Principle:

Principle #1Segmentation

2Measurement precision

If multiple antigens are targeted to improve specificity, then the discrimination between TME cells and healthy cells improves, but the time required for antigen selection and CAR T cell generation increases

Engineering Contradiction:

ImproveAntigen discrimination accuracyVSAvoidAntigen selection and CAR T cell generation time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary identification of patient-specific antigen combinations on tumor microenvironment cells before CAR T cell generation. By pre-selecting the optimal antigen pairs from known markers (CD10, PDGFRβ, etc.) and validating their specificity to TME cells, the method establishes a ready-to-use targeting strategy that accelerates the overall process while maintaining high discrimination accuracy.

Inventive Principle:

Principle #10Preliminary action

3Productivity

If CAR T cells are engineered to target TME cells with multiple antigens, then the ability to destroy TME barriers improves, but the complexity of antigen selection and CAR design increases

Engineering Contradiction:

ImproveTME destruction efficiencyVSAvoidAntigen selection and CAR design complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the parameters of antigen selection by focusing on a defined panel of TME-specific markers (CD10, PDGFRβ, etc.) and their expression patterns. By establishing quantitative thresholds and specific combination criteria for antigen co-expression on TME cells versus healthy cells, the method simplifies the complex antigen selection process while enhancing TME destruction efficiency through multi-antigen targeting.

Inventive Principle:

Principle #35Parameter changes

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

Enables rapid identification and engineering of CAR T cells that effectively kill TME cells with high specificity, reducing the risk of attacking non-tumor cells and enhancing cancer treatment efficacy.

Implementation Method 1

detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS20230076164A1Method for providing personalized cells with chimeric antigen receptors (CAR) against tumor microenvironment cells

Publication Date: 2023.03.09 MILTENYI BIOTEC BV & CO KG

AI summary

The invention is directed to a process for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor microenvironment cells characterized by providing a cell sample comprising tumor microenvironment cells and non-tumor microenvironment cells and repeating the steps of—contacting the cell tissue with a conjugate comprising a fluorescent moiety and an antigen recognizing moiety—removing unbound conjugate from the cell tissue and detecting cells bound to the conjugate by the fluorescence radiation emitted by the fluorescent moieties of the first conjugates—erasing the fluorescence emitted by the fluorescent moieties of the conjugates until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor microenvironment cells and non-tumor microenvironment cells and providing cells with the identified at least two antigen recognizing moieties as chimeric antigen receptor (CAR). Preferable, the tumor microenvironment cells are tumor microenvironment cells from tumor stromal cells or PaCa cells.