CAR T-Cell Specificity via Fluorescent Antigen Screening

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current CAR T-cell therapies face challenges such as non-specific surface molecules, variable tumor cell expression, antigen heterogeneity, and the need for personalized combinations, leading to inefficiencies and the potential for attacking healthy cells.

Innovation Solution

A method involving conjugates with fluorescent and antigen-recognizing moieties to identify specific antigens on cancer cells, enabling the engineering of CAR T-cells that target tumor cells with high specificity while minimizing non-tumor cell interaction, using a process that rapidly identifies optimal antigen combinations for personalized therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a single surface molecule is used as target for CAR T cells, then the therapy is simpler to implement, but the specificity is insufficient as the molecule can be expressed on non-tumor cells leading to safety problems

Engineering Contradiction:
ImproveCAR T cell therapy complexityVSAvoidtumor targeting specificity
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent segments the targeting function by using multiple independent CARs (first CAR and second CAR) that recognize different surface molecules. This segmentation allows the system to achieve high specificity through combinatorial recognition while maintaining manageable complexity by using standardized CAR constructs for each target.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a composite CAR T cell population that expresses multiple different CARs simultaneously. This composite approach combines the targeting capabilities of different CARs to achieve enhanced specificity, where the combined effect of multiple CARs provides reliable tumor targeting while each individual CAR maintains a manageable design.

Inventive Principle:
Principle #40Composite materials

2Reliability

If more than one surface molecule is targeted using dual CAR T cells, then the tumor targeting specificity is improved, but the complexity of developing personalized combinations increases significantly

Engineering Contradiction:
Improvetumor targeting specificityVSAvoidCAR T cell therapy complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs universal CAR constructs that can be applied across different cancer types by simply changing the antigen target. The standardized CAR design with common signaling domains and structural elements allows the same platform to target multiple different surface molecules, reducing the complexity of developing personalized combinations while maintaining high specificity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent changes the antigen target parameter while keeping the CAR structural parameters constant. By modifying only the antigen-binding domain to recognize different surface molecules while maintaining the same signaling and transmembrane domains, the system achieves personalized targeting without proportionally increasing overall complexity.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If personalized profiling of tumor marker expression is performed to account for antigen heterogeneity, then the tumor targeting accuracy is improved, but the time required for therapy development increases beyond acceptable clinical time frames

Engineering Contradiction:
Improvetumor marker expression profiling accuracyVSAvoidtherapy development time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary identification of suitable surface molecule targets using in vitro assays and computational analysis before committing to full-scale CAR T cell manufacturing. This preliminary screening of potential targets allows for accurate tumor marker profiling to be completed in advance, ensuring targeting accuracy while reducing the time required during the actual therapy development phase.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent accelerates the target identification process by using high-throughput screening methods and computational predictions to rapidly evaluate multiple surface molecules. This allows the essential tumor marker profiling to be rushed through in a compressed timeframe, maintaining measurement precision while minimizing the time loss in the overall therapy development process.

Inventive Principle:
Principle #21Skipping (Rushing through)

4Productivity

If the antigen recognition affinity is increased to ensure efficient T cell activation, then the tumor cell killing efficiency is improved, but the risk of attacking healthy cells expressing the antigen increases

Engineering Contradiction:
Improvetumor cell killing efficiencyVSAvoidoff-target cell attack risk
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the recognition function across multiple CARs with different antigen specificities. Each CAR can have moderate affinity for its specific target, but the combined action of multiple CARs on the same tumor cell achieves high overall killing efficiency. This segmentation reduces the risk to healthy cells because each individual CAR with moderate affinity is less likely to cause off-target effects.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies different affinity characteristics to different CARs based on the local requirements of their respective targets. Some CARs may have higher affinity for antigens that are rare on healthy cells, while others have lower affinity for more common antigens. This localized optimization of affinity for each CAR allows efficient tumor cell killing while minimizing overall risk to healthy cells.

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

This approach allows for the rapid identification and engineering of CAR T-cells that effectively target tumor cells with high specificity, reducing the risk of attacking healthy cells and enhancing the chances of destroying tumor cells, even if only a portion are identified, thereby improving the efficacy of cancer immunotherapy.

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

PatentEP3712617B1Method for providing personalized cells with chimeric antigen receptors (CAR)
Publication Date: 2022.01.26 MILTENYI BIOTEC BV & CO KG
  • EP3712617B1 patent drawingFigure 1
  • EP3712617B1 patent drawingFigure 2
  • EP3712617B1 patent drawingFigure 3

AI summary

The present invention is directed to a method for providing a cell comprising a chimeric antigen receptor (CAR) specific for one or more target antigens exposed on tumor cells characterized by providing a cell sample comprising tumor and non-tumor 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 with conjugates comprising a fluorescent moiety and antigen recognizing moieties recognizing different antigens until identifying at least two conjugates provided with antigen recognizing moieties recognizing different antigens, allowing in combination to discriminate between tumor cells and non-tumor cells and providing cells with the identified at least two antigen recognizing moieties as chimeric antigen receptor (CAR).