Modular CAR Library Design for Solid Tumor Efficacy

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Solution Overview

Problem

Current CAR T cell therapies have limited efficacy in treating solid tumors, necessitating more efficient and high-throughput strategies for identifying improved synthetic receptor designs.

Innovation Solution

Development of high-throughput and modular methods and compositions for barcode-trackable cellular receptor design, manufacture, and measurement, utilizing signaling domain oligonucleotides with Type IIs restriction sites and unique molecular identifiers, to create diverse chimeric antigen receptors with enhanced immunological signaling capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional CAR T cell therapy designs are used, then specific hematological malignancies can be treated, but efficacy in solid tumors is limited

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidapplicability to different cancer types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the CAR design into modular components (extracellular domain, transmembrane domain, signaling domain) that can be independently optimized and recombined. This modular architecture allows systematic exploration of different receptor designs for various cancer types, particularly enabling adaptation to solid tumors while maintaining the proven efficacy for hematological malignancies.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent creates a universal platform for CAR design that can be applied across different cancer types. By establishing standardized modular components and high-throughput screening methods, the system enables a single CAR design framework to be adapted for treating both hematological malignancies and solid tumors, expanding therapeutic versatility.

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

2Adaptability or versatility

If the space of possible synthetic receptor designs is fully explored, then improved therapeutic strategies can be identified, but current exploration is insufficient

Engineering Contradiction:
Improvereceptor design diversityVSAvoidscreening efficiency
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent performs preliminary actions by pre-designing and pooling diverse signaling domain variants before screening. The modular library approach allows extensive receptor design space to be prepared in advance, enabling comprehensive exploration of possible designs without requiring time-consuming individual characterization of each variant during the screening phase.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses barcode tracking systems that create molecular copies of receptor information. By associating unique barcodes with each receptor variant in the library, the system enables high-throughput copying and tracking of diverse receptor designs through pooled screens, dramatically increasing screening productivity while maintaining design diversity.

Inventive Principle:
Principle #26Copying

3Productivity

If high-throughput strategies are implemented, then identification of improved synthetic receptors is accelerated, but more efficient methods are required

Engineering Contradiction:
Improvescreening throughputVSAvoidmethod complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into a unified high-throughput screening platform. By combining modular library construction, barcode tracking, and pooled screening into an integrated system, the method achieves high productivity without proportionally increasing operational complexity. The standardized protocols and reusable components simplify the overall process despite the advanced capabilities.

Inventive Principle:
Principle #5Merging (Combining)

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 the identification and production of recombinant immune cells with improved properties such as cellular proliferation, resistance to exhaustion, antigen specificity, and targeted killing capabilities, facilitating more effective cancer treatment.

Implementation Method 1

Type IIs restriction site for a first Type IIs restriction enzyme

Methodology Applied
Scientific EffectRestriction enzyme cleavage: Enzyme

Data Source

PatentUS20240301403A1Method for making car-t libraries
Publication Date: 2024.09.12 RGT UNIV OF CALIFORNIA
  • US20240301403A1 patent drawing
  • US20240301403A1 patent drawing
  • US20240301403A1 patent drawing

AI summary

This disclosure generally relates to high-throughput and modular methods and compositions for barcode-trackable cellular receptor design, manufacture, and measurement.