ROR1 CAR T Cells Preventing Antigen Escape

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Solution Overview

Problem

Current treatments for tumors with high expression of Receptor tyrosine kinase-like orphan receptor 1 (ROR1) or both ROR1 and CD19 face challenges in effectively targeting these antigens due to antigen escape and cytotoxicity concerns, necessitating a more robust and selective therapeutic approach.

Innovation Solution

Development of a chimeric antigen receptor (CAR) that specifically binds to ROR1 or dual targets ROR1 and CD19, comprising a signal peptide, hinge domain, transmembrane domain, and intracellular domain, with specific antibody or antigen-binding fragments, to enhance targeting efficacy and reduce cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional CAR T-cell therapy targets single antigens, then treatment simplicity is maintained, but antigen escape occurs reducing therapeutic efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidCAR structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines two separate CAR structures into a dual CAR T-cell that simultaneously targets both ROR1 and CD19 antigens. This merging approach prevents antigen escape by ensuring tumor cells must lose both antigens to evade therapy, thereby improving therapeutic reliability without proportionally increasing structural complexity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The dual CAR T-cell achieves multi-functionality by incorporating antigen recognition domains for both ROR1 and CD19 within a single cell product. This universal approach allows the therapy to address multiple antigen loss mechanisms and provides backup targeting pathways, enhancing overall therapeutic efficacy

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If CAR T-cells are designed for high antigen binding affinity, then tumor targeting is improved, but cytotoxicity towards normal cells increases

Engineering Contradiction:

Improveantigen binding specificityVSAvoidcytotoxicity to normal cells

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making the CAR structure heterogeneous at the antigen recognition level - one CAR component targets ROR1 with high specificity while another targets CD19. This localized differentiation in antigen binding properties allows the system to maintain high precision for tumor targeting while the dual-targeting architecture inherently limits off-target cytotoxicity to cells expressing both antigens

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The dual CAR system acts as an intermediary safety mechanism where the requirement for simultaneous recognition of both ROR1 and CD19 antigens creates a more restrictive binding condition. This intermediary layer of dual antigen recognition reduces the likelihood of accidental binding to normal cells that may express one antigen at low levels, thereby reducing harmful cytotoxicity

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240342283A1ROR1 CAR or ROR1 / CD19 Dual CAR T Cells for the Treatment of Tumors

Publication Date: 2024.10.17 SHANDONG BIOANTY BIOLOGICAL TECH CO LTD

AI summary

An ROR1 CAR or ROR1/CD19 Dual CAR for the treatment of tumors. The T cells expressing ROR1 CAR or ROR1/CD19 Dual CAR can be stimulated by ROR1-positive or ROR1/CD19-positive cells, and have cytotoxicity against ROR1-positive or ROR1/CD19-positive cells.