Chimeric Antigen Receptor Domains for Dual BCMA/CD19 Targeting

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Solution Overview

Problem

Existing methods for producing CAR-expressing cell therapy products in adoptive cell transfer therapy are limited in enhancing product quality and maximizing therapeutic efficacy.

Innovation Solution

Engineering immune cells, such as T cells or NK cells, with chimeric antigen receptors (CARs) that incorporate specific antigen-binding domains, including anti-BCMA and anti-CD19 binding domains, to enhance targeting and therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR therapy methods are used, then basic therapeutic effect is achieved, but product quality and therapeutic efficacy are limited

Engineering Contradiction:

Improveproduct qualityVSAvoidtherapeutic efficacy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent divides the antigen-binding function into separate domains (first antigen-binding domain for BCMA, second antigen-binding domain for CD19) that can be independently optimized and combined in different CAR configurations, allowing independent improvement of each binding specificity while maintaining overall therapeutic efficacy

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention creates CARs that can target multiple antigens (BCMA and CD19) through different antigen-binding domains, enabling a single cell therapy product to address multiple tumor markers and improve both product quality consistency and therapeutic efficacy across different cancer types

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If multiple antigen-binding domains are incorporated into CARs, then targeting specificity is improved, but CAR structure complexity increases

Engineering Contradiction:

Improvetargeting specificityVSAvoidCAR structure

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The antigen-binding function is segmented into distinct domains (first and second antigen-binding domains) that can be independently designed and tested, then combined in modular CAR structures, making the complex multi-specific CAR constructible from standardized parts

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs nested linker regions that connect the different antigen-binding domains in a hierarchical manner, where linkers are inserted between domains to maintain proper spatial arrangement while simplifying the overall structural organization of multi-specific CARs

Inventive Principle:

Principle #7Nested doll (Nesting)

Data Source

PatentUS12383601B2Chimeric antigen receptors and uses thereof

Publication Date: 2025.08.12 NOVARTIS AG

AI summary

The invention provides immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions and methods thereof.