Anti-ROR1 CAR-T and CAR-NK Cells for Persistent Tumor Targeting

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Solution Overview

Problem

Current CAR-T cell and CAR-NK cell therapies targeting tumor-associated antigens face challenges such as anaphylaxis and limited persistence, while ROR1, a receptor overexpressed in various cancers, offers a promising target but requires effective antibody and receptor designs for enhanced cytotoxicity and specificity.

Innovation Solution

Development of anti-ROR1 antibodies and chimeric antigen receptors (CARs) with specific scFv domains, co-stimulatory, and activation domains, engineered into immune cells like CAR-T and CAR-NK cells, to target ROR1-positive cancer cells with enhanced cytotoxic activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

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

Engineering Contradiction:

Improveantitumor activityVSAvoidanaphylaxis and limited persistence

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by developing a novel anti-ROR1 antibody (PMCAE8) with modified amino acid sequences that alter the binding characteristics and reduce immunogenicity. The antibody sequence identity parameters are controlled at 90-99% to balance affinity and reduced anaphylaxis risk, directly addressing the harmful effects while maintaining antitumor activity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by constructing chimeric antigen receptors that combine multiple functional domains: the anti-ROR1 antibody-derived scFv for antigen recognition, hinge regions for flexibility, transmembrane domains for cell membrane integration, and intracellular signaling domains (CD3ζ, CD28, 4-1BB) for activation and costimulation. This composite structure enhances both persistence and antitumor activity while reducing harmful effects

Inventive Principle:

Principle #40Composite materials

2Reliability

If ROR1 is targeted for cancer therapy, then cytotoxicity against cancer cells is improved, but effective antibody and receptor designs are required to enhance specificity

Engineering Contradiction:

Improvecytotoxicity against cancer cellsVSAvoidantibody and receptor design specificity

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by optimizing specific regions of the antibody molecule, particularly the complementarity-determining regions (CDRs) and framework regions. The amino acid sequences are locally modified to enhance binding affinity and specificity for ROR1 while maintaining overall structural integrity, achieving high cytotoxicity with improved design precision

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent replaces traditional mechanical antibody design approaches with engineered chimeric antigen receptors that integrate molecular recognition and signaling functions. The CAR system substitutes simple antibody binding with a complex receptor system that includes transmembrane anchoring and intracellular signaling domains, enhancing both specificity and cytotoxicity

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS12492264B2Anti-ROR1 antibody and ROR1-targeting engineered cells

Publication Date: 2025.12.09 CARIBOU BIOSCIENCES INC

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.