CAR Cell Library with Genetic Circuits for Antigen Heterogeneity

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Solution Overview

Problem

Current CAR cell therapy technologies face challenges in identifying and targeting specific antigens due to antigen heterogeneity, variability, and evolvability in malignant tumors, leading to inefficiencies in treatment and limited individualized therapeutic strategies.

Innovation Solution

A CAR cell library is developed with a genetic element combination comprising idiotype CARs, unique genetic circuits, and inducible proteins, allowing for programmable expression regulation and adaptive response to antigen changes, enabling the library to target individualized antigens effectively.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single antigen-targeted CAR is used, then the treatment is simple and easy to manufacture, but the therapy fails due to antigen heterogeneity, variability, and evolvability in malignant tumors

Engineering Contradiction:

Improvesimplicity of CAR therapy preparationVSAvoideffectiveness of antigen-targeted CAR therapy

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a universal CAR cell library that can target multiple different antigens simultaneously. The library contains CARs with diverse antigen-specific binding domains, allowing a single therapeutic product to address antigen heterogeneity and variability across different tumor types and stages, while maintaining a standardized manufacturing process.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent introduces dynamic selection mechanisms where the immune system can adaptively choose which CARs from the library are most effective against the patient's specific tumor antigens. This dynamic adaptation allows the therapy to respond to antigen evolvability and heterogeneity, overcoming the limitations of fixed single-antigen CAR approaches.

Inventive Principle:

Principle #15Dynamics

2Adaptability or versatility

If a CAR library targeting multiple antigens is developed, then the adaptability to antigen variations is improved, but the device complexity and screening difficulty increase

Engineering Contradiction:

Improveability to target diverse and variable antigensVSAvoidcomplexity of CAR library construction and screening

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the complex task of targeting multiple antigens into manageable modular CAR units, each targeting a specific antigen. These modular CARs are organized in a library format, allowing systematic construction and screening. The segmentation approach simplifies the overall complexity by breaking down the multifunctional requirement into discrete, testable components.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses copying strategies where successful CAR designs are replicated and varied systematically to create the library. Standardized CAR backbones are copied and combined with diverse antigen-specific binding domains, reducing the complexity of designing each CAR from scratch while maintaining adaptability to multiple antigens.

Inventive Principle:

Principle #26Copying

3Adaptability or versatility

If a large-scale CAR library is constructed, then the coverage of unknown and diverse antigens is improved, but the screening time and resource requirements increase

Engineering Contradiction:

Improvecoverage of unknown and diverse tumor antigensVSAvoidtime required for library screening and identification of effective CARs

Core Design Contradiction:

Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent performs preliminary actions by pre-construcing the CAR library with diverse antigen targets before patient treatment. The library is prepared in advance with CARs targeting known and predicted tumor antigens, allowing rapid deployment and screening in clinical settings without time-consuming de novo design and testing.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback mechanisms where screening results from patient responses guide further library development and refinement. Effective CARs identified through screening are fed back into the library design process, improving future library compositions and reducing screening time for subsequent therapeutic developments.

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20220348961A1Chimeric antigen receptor cell library carrying gene element combination, prepration and screening method, and use thereof

Publication Date: 2022.11.03 PHARCHOICE THERAPEUTICS INC

AI summary

A chimeric antigen receptor (CAR) cell library is established through the fusion of a cell and a vector assembly. The vector assembly carries three genetic elements corresponding to a plurality of first genetic elements encoding one or more idiotype CARs, a second genetic element carrying one or more genetic circuits, and a third genetic element encoding one or more inducible proteins, respectively. The one or more genetic circuits are pre-programmed and are each a combination of a cis-regulatory factor and a transcription factor; and the one or more inducible proteins include one or two selected from the group consisting of a drug resistance protein and a suicide protein. By designing a CAR library-genetic circuit-inducible protein coupling scheme, the cell library construction and screening for complex and unknown disease target antigens are realized, such as to solve the problems that there are complex, diverse, and variable antigens.