Chimeric Antigen Receptor for T Cell-Independent B Cell Activation

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Solution Overview

Problem

Current B cell engineering techniques rely on T cell help for antigen-induced activation, which is limiting in conditions like immune tolerance, immunocompromised patients, and cancer, where T cell assistance is absent or suppressed.

Innovation Solution

Development of a chimeric antigen receptor (CAR) molecule for B cells that includes a target-binding domain, transmembrane domain, and a signal transduction domain capable of T cell-independent activation, allowing B cells to activate without T cell assistance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If B cells are engineered with conventional B cell receptor (BCR) complex signal transduction domains, then the B cells can recognize antigens, but activation remains dependent on T cell help

Engineering Contradiction:

Improveactivation independenceVSAvoidapplicability in immune-compromised conditions

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the signal transduction domain parameters by replacing conventional BCR complex domains with alternative domains (such as CD3 zeta chains or other signaling domains) that can initiate activation cascades independent of T cell help, fundamentally altering the activation mechanism to work in immune-compromised conditions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The chimeric antigen receptor is segmented into distinct functional domains: an antigen recognition domain (from BCR or antibody) and a signal transduction domain (from T cell receptors or other sources), allowing independent optimization of each function and enabling T cell-independent activation while maintaining antigen specificity

Inventive Principle:

Principle #1Segmentation

2Ease of manufacture

If B cells rely on T cell help for activation, then activation can be tightly regulated in germinal centers, but this dependency limits utility in conditions where T cells are absent or suppressed

Engineering Contradiction:

Improvetherapeutic applicabilityVSAvoidactivation reliability

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The engineered B cells possess universal activation capability through the chimeric receptor design that can function both in normal immune conditions (with T cell help) and in pathological conditions (without T cell help), making the therapy broadly applicable across different disease states and patient populations

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250099503A1Engineering b cells to express chimeric antigen receptors (CARS) and uses thereof for t cell independent activation

Publication Date: 2025.03.27 RAMOT AT TEL AVIV UNIVERSITY LTD

AI summary

The present disclosure describes a chimeric antigen receptors (CAR) that allow a cell of the B cell lineage to undergo antigen-induced activation independent of a cell of T cell lineage, compositions thereof, and method of use thereof for genetically modifying a cell of the B cell lineage or treating a subject suffering from a pathological disorder.