Anti-ROR1 CAR-T and CAR-NK Cells for Specific Persistent Tumor Killing

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Solution Overview

Problem

Current CAR-T cell therapies targeting tumor-associated antigens face challenges such as anaphylaxis and limited persistence, while natural killer (NK) cells lack specificity and efficacy against cancer cells overexpressing ROR1.

Innovation Solution

Development of anti-ROR1 antibodies and chimeric antigen receptors (CARs) that specifically target ROR1, incorporating scFv, transmembrane, and co-stimulatory domains, engineered into CAR-T and CAR-NK cells to enhance cytotoxic activity and persistence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CAR-T cells are used to target tumor-associated antigens, then anti-tumor activity is improved, but anaphylaxis occurs and persistence is limited

Engineering Contradiction:

Improveanti-tumor activityVSAvoidanaphylaxis

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by using highly specific anti-ROR1 antibodies that selectively bind only to ROR1-expressing cancer cells, avoiding cross-reactivity with normal tissues. This localized specificity reduces systemic immune activation and anaphylaxis while maintaining potent anti-tumor cytotoxicity through targeted engagement of CAR-T cells with ROR1-positive cells

Inventive Principle:

Principle #3Local quality

2Reliability

If CAR-T cells are used to target tumor-associated antigens, then anti-tumor activity is improved, but persistence in the patient is limited

Engineering Contradiction:

Improveanti-tumor activityVSAvoidpersistence

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent employs composite CAR结构设计 that integrates multiple functional domains: the anti-ROR1 scFv for specific antigen recognition, hinge region for flexibility, transmembrane domain for proper positioning, and intracellular signaling domains (CD3ζ for activation, CD28 or 4-1BB for costimulation) for sustained T cell activation and persistence. This composite structure enables both potent immediate cytotoxicity and long-term persistence of CAR-T cells in the patient

Inventive Principle:

Principle #40Composite materials

3Speed

If natural killer cells are used, then rapid response is achieved, but specificity and efficacy against ROR1-overexpressing cells is insufficient

Engineering Contradiction:

Improveresponse speedVSAvoidspecificity

Core Design Contradiction:

SpeedVSReliability

Solution Approach 1:

The patent uses the anti-ROR1 antibody-derived scFv as an intermediary component in the CAR structure that confers specific recognition of ROR1-expressing cells to NK cells. This intermediary antigen-binding domain enables CAR-NK cells to maintain the rapid response capability of natural killer cells while gaining target-specific recognition and enhanced efficacy against ROR1-overexpressing cancer cells

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250339465A1Anti-ROR1 antibody and ROR1-targeting engineered cells

Publication Date: 2025.11.06 PROMAB BIOTECH

AI summary

The present invention is directed to a monoclonal mouse or humanized ROR1 antibody, or a single-chain variable fragment (scFv). The present invention is also directed to a mouse or humanized ROR1 chimeric antigen receptor (CAR) comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain.